Chemoselective synthesis of isolated and fused fluorenones and their photophysical and antiviral properties

Article abstract of DOI:10.1039/C8OB01733F

Highly functionalized fluorenones were synthesized by an intramolecular cyclization of 2′′-halo-[1,1′:3′,1′′-terphenyl]-4′-carbonitriles in the presence of n-butyllithium or lithium aluminium hydride. The precursor was synthesized by ring transformation o

Full text of DOI:10.1039/C8OB01733F

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2018, DOI: 10.1039/C8OB01733F.
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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Chemoselective synthesis of isolated and fused fluorenones
and their photophysical and antiviral properties
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
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Ismail Althagafi,a,* Ranjay Shaw,b,† Cheng-Run Tang,c,e Rahul Panwar,b Shally,b Chanda Sinha,b Amit
Kumar,d Yong-Tang Zheng,c,* Ramendra Pratapb,*
Highly functionalized fluorenones was synthesized by intramolecular cyclization of 2''-halo-[1,1':3',1''-terphenyl]-4'-
carbonitriles in presence of n-butyllithium or lithium aluminium hydride. The precursor was synthesized by ring
transformation of 2-oxo-6-aryl/heteroaryl-4-(sec.amino)-2H-pyran-3-carbonitriles or 2-oxobenzo[h]chromenes with o-
bromo/chloro/fluoro-acetophenone under basic conditions in moderate yield. We performed the control experiment to
understand the proposed mechanism and found that presence of scondary amine in the starting material direct the
reactivity. Photophysical properties of 3-methoxy-7-(piperidin-1-yl)-5H-indeno[2,1-b]phenanthren-8(6H)-one was explored
and solvent dependent emission was observed . These compounds were also tested against HIV-1 and low to moderate
activity was observed.
Various strategies for the synthesis of fluorenones was
established, such as ionic and radical cyclization of biaryl
carbonyls9 and nitriles,10 oxidation of fluorenes,11 ring
Introduction
Recently, fluorenones and its derivatives received wide
attention due to their potential applications in molecular
switches (figure 1),1 photophysics,2 crystal engineering3 and
biological and pharmaceutical science.4 Interestingly,
incorporation of electron donating and withdrawing groups in
fluorenone can tune its photophysical properties and become
more applicable for solar cell, OLEDs, organic laser and
florescence probes.2,5 The fluorenone based polyesters fibers
exhibit outstanding fire resistance properties with high glass
transition temperature and self-extinguishing behavior.6
contraction of phenanthraquinones,9f,12 dehydrogenative13 and
O
NaO
O
Cl
Cl
b
a
in vivo treatment of spinal
Light-driven molecular motor
or brain ischemia.
O
N
O
N
Recently,
R-(+)-(5,6-dichloro-2,3,9,9a-tetrahydro-7-hydroxy-
O
O
9a-hydrocarbyl-1H-fluoren-3-one was tested in vivo against
animal spinal and brain ischemia and demonstrated 30 times
better result than usual known drug (figure 1).7 Some other
important fluorenone based molecules are known for antiviral
activity (figure 1)8 and cardio-depressant behaviour (figure
1).4c
O
O
O
c
O
N
Antiviral
H
d
Cardiodepressant
Figure 1. Some useful fluorene and fluorenone based compounds (a) (S)-9-(2-phenyl-
2,3-dihydro-1H-cyclopenta[a]naphthalen-1-ylidene)-9H-fluorene; (b) GERI-E4; (c)
Tilorone; (d) Fluodipine
aDepartment of Chemistry, college of applied science, Umm Al-Qura University,
Makkah, Saudi Arabia
bDepartment of Chemistry, University of Delhi, North Campus, Delhi, India-110007
cKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese
Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences,
Kunming, China
dehydrohalogenative14 annulation of various benzophenones.
Among these methods, acid (specially acids of phosphorus)
mediate intramolecular acylation of biarylcarboxlic acids9b,15
and nitriles10c,d,e are most effective and widely used approach.
Some metal catalyzed annulation9d,10a,b was also reported but
base mediate anionic cyclization of biarylnitriles and carboxilc
acids to fluorenone are very rare.16 Anionic annulation of 2'-
halo-[1,1'-biphenyl]-2-carbonitriles have been tried but the
reagents selectively attacked on nitrile rather than halide and
phenanthridines or phenanthridinones was obtained as sole
dDepartment of Chemistry, Indian Institute of Technology, Patna, Bihar, India
eSchool of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for
Natural Products, Kunming Medical University, Kunming, Yunnan 650500, China.
† Ranjay Shaw should be considered as first author.
*Corresponding authors.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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sproduct. Recently, Heish and co-workers developed ligand- It was reported that ring transformation reactions of
free copper-catalyzed annulation of 2'-bromo-[1,1'-biaryl]-2- functionalized 2H-pyran-2-ones with various ketones under
carbonitriles to phenanthridinones17 and phenanthridines.18
A
basic conditions provides functionalized teraryls.23 Herein, We
Hydride-induced anionic cyclization of the 2'-bromo-[1,1'- have developed a base mediated regioselective approach for
biaryl]-2-carbonitriles also provide phenanthridines.19 Begtrup the synthesis of 2''-halo-5'-(sec.amino)-[1,1':3',1''-teraryl]-4'-
et al reported that reaction of Grignard reagent and alkyl carbonitriles. As a trial, we have performed the reaction of
lithium (R-Li; R=aryl, alkyl and sec.amine) chemoselectively compound
4 and 2’-bromoacetophenone (5a) in DMSO using
attack over the nitrile group of 2'-fluoro-[1,1'-biphenyl]-2- KOH as a base and moderate yield of 2''-bromo-4-methyl-5'-
carbonitriles.20 Cally et al reported a potassium hydroxide (piperidin-1-yl)-[1,1':3',1''-terphenyl]-4'-carbonitrile
(6d) was
mediate Microwave assisted ring closure of 2'-fluoro-[1,1'- afforded.
biphenyl]-2-carbonitriles21 to afford phenanthridine. On the To optimize the reaction condition, we have tried various
other hand, fluorenone was obtained by palladium catalyzed base/solvent combinations (SI, Table 1). We have used polar
anionic annulation of 2'-iodo-[1,1'-biphenyl]-2-carbonitriles.22 and nonpolar solvents like THF, dioxane, DMF and DMSO in
Due to wide range of application, we became interested in combinations of different bases such as sodium hydride,
development of new protocol for the synthesis of fluorenone. sodium hydroxide, potassium hydroxide, potassium carbonate
Herein, we have reported substituent dependent transition and cesium carbonate. The KOH in DMSO at room
metal free, anionic cyclization of 2'-halo-[1,1'-biphenyl]-2- temperature was found as best reaction condition and 66% of
carbonitriles to fluorenones through chemoselective lithiation the desired product 6a was afforded (SI, Table 1, entry 4). We
of halide.
Results and discussion
proposed that moderate yield was obtained probably due to
presence of bulky halo group at ortho position of
acetophenone. Taking the best reaction conditions, we have
To start our study, we have synthesized suitably functionalized
2'-halo-[1,1'-biphenyl]-2-carbonitriles. Various transition metal
mediated approach for the synthesis of 2'-halo-[1,1'-biphenyl]-
2-carbonitriles was reported, Herein, we have reported ring
transformation strategy to afford the required precursor.
Suitably functionalized 2'-halo-[1,1'-biphenyl]-2-carbonitriles
were synthesized from 2-oxo-6-aryl-4-(sec.amino)-2H-pyran-3-
carbonitriles. The precursor 2-oxo-6-aryl-4-(sec.amino)-2H-
pyran-3-carbonitriles was synthesized in two steps. First step
was preparation of 2-oxo-6-aryl-4-methylsulfanyl-2H-pyran-3-
carbonitriles or 2-oxo-4-methylthio-benzo[h]chromenes by
synthesized
a series of 2''-halo-5'-(sec.amino)-[1,1':3',1''-
teraryl]-4'-carbonitriles in moderate to good yield. All the
synthesized compounds were characterized by spectroscopic
analysis and structure of the compound 6d was confirmed by
single crystal X-ray.
Scheme 2. Synthesis of various 2''-halo-5'-(sec.amino)-[1,1':3',1''-teraryl]-4'-
carbonitriles (6)
N
N
O
X
CN
CN
O
KOH / DMSO
T oC / t h
reaction of ketenedithioacetal (
1) and various acetophenones
O
Ar
Ar
or tetralones (2) under basic conditions. In the next step,
X
4
5
6
obtained compound was refluxed with various secondary
amine in ethanol to afford 2-oxo-6-aryl-4-(sec.amino)-2H-
N
N
N
CN
CN
CN
pyran-3-carbonitriles
and
2-oxo-4-(sec.amino)-
benzo[h]chromenes (Scheme 1).
O
Br
6g
; Piperidine; 69%
Br
Br
; Piperidine; 66%
6d
6d
6e; pyrrolidine; 62%
6a; Piperidine; 57%
6b; pyrrolidine; 53%
Scheme 1. Synthesis of 2-oxo-6-aryl-4-(sec.amino)-2H-pyran-3-carbonitriles and
2-oxo-4-(sec.amino)-benzo[h]chromenes (4)
6h; Pyrrolidine; 63%
6f
6c
; Morpholine; 57%
; Morpholine; 48%
O
S
N
CN
CN
O
O
N
N
CN
KOH / DMSO
rt/18-24h
CN
CN
S
Ar/HetAr
EtO
S
O
Br
Ar/HetAr
S
Br
3
Cl
Br
6i; 54%
O
6k
; Piperidine; 67%
6l; Pyrrolidine; 64%
2
1
6
j; 58%
EtOH
N
H
N
N
N
N
CN
CN
CN
CN
N
CN
Br
O
Br
S
X
X
6n
; Piperidine; 58%
6o; Pyrrolidine; 56%
6
r; X = F; 63%
6s; X = Cl; 70%
O
O
6p; X = F; 67%
6q; X = Cl; 73%
6m; 61%
Ar/HetAr
4
Once desired precursor was prepared, we studied the
intramolecular cyclization approach under various conditions.
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aThe reaction was conducted with 2''-bromo-4-methyl-5'-(piperidin-1-yl)-
[1,1':3',1''-terphenyl]-4'-carbonitrile (0.3 mmol) in 1.5 mL solvent; bRoom
temperature varies from 30-35oC; cYield of isolated product reported.
We used 2''-bromo-4-methyl-5'-(piperidin-1-yl)-[1,1':3',1''-
terphenyl]-4'-carbonitrile as a model substrate to study the
intramolecular cyclization. As per earlier report, in the
expectation of formation of phenanthridine, we treated the
starting material with different amount of Li(Et)3BH in THF at
100 oC for 24 h, but surprisingly another product functionalized
fluorenone (8d) was isolated in 15% and 36 % yield (Table 1,
entry 1-3). Further, we used sodium borohydride but no
reactions were observed (Table 1, Entry 4). Then, we have
tried lithium aluminium hydride in THF at room temperature
and no reaction was observed (Table 1, entry 5), but at higher
temperature and ratio, moderate yield of fluorenone was
Scheme 3. Synthesis of various functionalized fluorenones
N
N
CN
O
n-BuLi
THF
Ar/
HetAr
Ar/
HetAr
Br
6
8
O
N
Table 1. Optimization of the reaction conditionsa
N
N
O
O
O
8b, 61%
8c, 66%
8a,64%
O
N
Temp. (oC)
Time (h)
Yieldc
(%) 8d
N
S.N.
Reagent
(eq.)
Solvent
N
O
O
O
1
Li(Et)3BH 1.1
Li(Et)3BH 2.0
Li(Et)3BH 3.0
THF
100
24
trace
8e, 62%
8f, 65%
8d,67%
2
3
4
5
THF
THF
THF
THF
100
36
36
36
12
15
36
-
O
N
N
100
O
N
O
O
NaBH4
LiAlH4
3.0
1.1
130-140
rtb
O
Cl
O
8h, 59%
8i, 49%
8g, 61%
-
6
LiAlH4
LiAlH4
LiAlH4
LiAlH4
LiAlH4
LiAlH4
LiAlH4
LiAlH4
n-BuLi
n-BuLi
1.1
2.0
3.0
4.0
3.0
3.0
3.0
3.0
1.5
2.0
THF
THF
THF
THF
THF
60
60
60
60
100
12
12
12
12
12
12
12
12
3
Trace
34
N
N
N
O
O
O
7
S
S
8
55
8k, 67%
8l, 64%
8j, 58%
9
47
N
N
N
O
O
O
10
11
12
13
14
15
42
Dioxane 60
Hexane 60
Benzene 100
40
O
O
8o, 56%
8n, 55%
8m, 60%
32
obtained (Table 1, entry 6-10). We also used other solvent like
1,4-dioxane, hexane and benzene in lieu of THF but no
improvement was recorded (Table 1, entry 11-13). As we
notice that first step is generation of phenyl anion/radical, we
plan to use n-butyllithium as a base. A smooth reaction offered
38% of fluorenone in presence of 1.5 equivalent of n-BuLi at -
75 oC to room temperature (Table 1, entry 14). The yield of
fluorenone was improved to 67% by using 3 equivalent n-BuLi,
but further increase in the amount of reagents lowers the yield
(Table 1, entry 15-17). A comparable yield of 8d was observed
in 1,4-dioxane under similar reaction condition, but low yield
was observed in hexane (Table 1, entry 18-19).
27
THF
-75 to rtb
38
THF
-75 to rtb
-75to rtb
-75 to rtb
-75 to rtb
3
55
16
17
18
19
n-BuLi
n-BuLi
n-BuLi
n-BuLi
3.0
4.0
3.0
3.0
THF
3
3
3
3
67
57
25
61
THF
Hexane
Dioxane -75 to rtb
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After optimization, the scope of the reaction was investigated 4). This change in the selectivity of n-BuLi from previous
with different functionalized 2'-bromo-5-aryl-3-sec.amino- report20a is attributed probably due to presence of secondary
biaryl-2-carbonitriles (scheme 3).
amine at ortho position of nitrile, which make the nitrile group
Various fused and isolated fluorenone (8a-o) was synthesized electron rich and anion attack was not possible. To examine
in moderate to good yield. It was observed that presence of the influence of halide, the fluoro derivative 6p and 6r were
various aryl/heteroaryl group and secondary amine group can treated with n-BuLi under similar condition and corresponding
be tolerated under the optimized reaction condition. These fluorenone 8d and 8k were obtained in 57% and 60%
groups also do not affect the yield of desired product. The respectively (scheme 5), whereas corresponding chloro
similar protocol was also applied for the synthesis of 6- derivatives 6q and 6s furnish 61% and 63% yield of 8d and 8k
sec.amino-12,13-dihydro-indeno[1,2-a]phenanthren-7-ones
respectively (scheme 5). This result confirms that the
(
8m-o) and good yield was obtained. It was reported that chemoselectivity was achieved by presence of secondary
presence of electron donating amine group at ortho position amine at ortho of nitrile group and no role of halide occurs.
of fluorenone furnished an important class of florescence We wanted to understand the mechanistic pathway involved
compounds.24 Along with the florescence property, the bulky during use of lithium alminium hydride. As per literature
ortho substitution also makes it applicable for the synthesis of report,25 we proposed that radical mediated reaction is
molecular motors or photoswitches.
probably involved (scheme 6) and reaction is initiated by single
electron transfer from Br group by interaction with LAH. In the
next step bromide ion was lost with the formation of aryl
radical, which can further interact with LAH to provide aryl
anion, which attack on the nitrile group present in the adjacent
Scheme 4. Proposed mechanistic pathway for the synthesis of fluorenone with n-
BuLi
ring to provide intermediate
B. The intermediate B hydrolysed
on wok-up to afford the fluorenone.
Scheme 6. Proposed mechanistic pathway for the synthesis of fluorenone with
LiAlH4
We tried to understand the mechanistic pathways involved in
cyclization by lithium aluminium hydride and n-BuLi. Earlier
literatures17-21 shows that n-alkyl lithium and hydride reagent
chemoselectively react with nitrile group of 2'-halo-[1,1'-
biphenyl]-2-carbonitriles
followed
by
dehalogenative
annulation to afford phenanthridine or phenanthridinone.
Even n-BuLi was also found selective to nitrile of 2'-fluoro-
[1,1'-biphenyl]-2-carbonitrile.20a Interestingly, in our case, n-
To support the mechanism, we performed some control
reactions. Treatment of 4-methyl-5'-(piperidin-1-yl)-[1,1':3',1''-
Scheme 5. Synthesis of fluorenone from 6p-6r
terphenyl]-4'-carbonitrile
9 with n-BuLi provides no reaction
and 95% starting material was recovered along with very small
amount of unidentified side products. This reaction indicates
that the anionic attack of n-BuLi on the nitrile group is not
possible due to presence of secondary amine at ortho position
[Scheme 7, (i)]. Further to trap the proposed anion, 2'-bromo-
3-(piperidin-1-yl)-5-(thiophen-2-yl)-[1,1'-biphenyl]-2-
carbonitrile 6k was treated with n-BuLi at -78 oC and quenched
the reaction with D2O after 30 minute and a mixture of 8k
(35%) and 10 (23%) was obtained [Scheme 7,(ii)]. Formation of
product 10 confirmed that the reaction proceed via
BuLi provides chemoselective lithiation of halide of compound
intermediate
A (Scheme 4). To confirm the reaction pathway
6
, instead of nitrile and gives intermediate
expected intermediate . Then, we proposed that anionic
annulation of intermediate occurs by involvement of nitrile
group in adjacent ring to furnish . The imine thus formed
A rather than the
of Scheme 6, three equivalent of LiAlH4 was added to 6k under
standard protocol and 5 equivalent TEMPO was added after 30
minute. Almost 80% of the starting material was recovered
with some decomposition after 15 hours of reaction (Scheme
C
A
B
undergoes hydrolysis to afford the desired product
8 (scheme
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7,(iii)). We proposed that LAH is probably quenched by TEMPO measured by the syncytia formation assay. In the presence or
and no reaction was observed, which support the radical absence of various concentrations of samples, five testing
mechanism.
samples (6b, 6l, 8e, 8i and 8m) showed cytotoxicity on C8166
with CC50 values between 46μM to 80μM. The remaining
samples had very low cytotoxicity on C8166 and the CC50 value
Scheme 7. Control reactions in support of mechanism
1.2
DCM
DMSO
DMF
Hexane
1.0
0.8
0.6
0.4
0.2
0.0
250
300
350
400
450
500
550
Wavelength(nm)
Figure 2. UV-Visible Spectra of 8n
This class of molecules are very florescent so we studied the
property of one molecule. The UV-visible spectra and
florescence spectra of 0.25 µM solution of 3-methoxy-7-
350
467 nm
DCM
DMF
DMSO
Hexane
300
250
200
150
100
50
(piperidin-1-yl)-5H-indeno[2,1-b]phenanthren-8(6H)-one
8n
530nm
was recorded in different solvent system at room temperature
444nm
502nm
Table 2. Photophysical property of 8n
abs
max
λ
Solvent
Hexane
(nm)
(nm)
444
Stokes shift(nm)
9
435
DCM
DMF
439
447
450
467
502
530
28
55
80
0
DMSO
350 400 450 500 550 600 650 700
Wavelength (nm)
and summarized in table 2. The UV-visible absorption
spectrum shows the different absorption band in the different
solvents for same compound and peak at 435 nm, 439 nm, 447
nm and 450 nm was observed in hexane, DCM, DMF and
DMSO respectively. From this result, it was revealed that the
polar solvents pull the absorption band towards the higher
wavelength of the absorption spectrum. As shown in the figure
2, the solvent did not produce any significant change in the
absorption spectrum of the receptor 8n. The polarity of the
solvents does not show any significant change in the λmax value
of UV-visible absorption spectra of 8n (figure 2). The λmax for
emission spectra of 8n was recorded at 444 nm, 467 nm, 502
nm and 530 nm in hexane, DCM, DMF and DMSO, respectively
and a noticeable red shift was observed in the florescence
maxima (λmax) with polarity of solvents.
Figure 3. Florescence Spectra of 8n
of them were higher than 200μM. Compound 6d, 6g, 6k, 6m,
8d and 8n showed weak to moderate anti-HIV-1 activity and
their therapeutic index were >14.21, >46.19, >47.96, >21.51,
>10.10, >13.74 respectively. As a control, AZT has the best
anti-HIV activity (EC50 = 0.01008μM) in vitro and the CC50 of it
is 3695.04μM, its therapeutic index is 366571.43.
Conclusions
In conclusion, we have developed a novel and transition metal
free method for chemoselective synthesis of various isolated
and fused fluorenones (8a-o) in moderate to good yield via n-
BuLi mediated anionic ring closure. From this reaction, we
have also concluded the presence of electron donation group
at ortho and para position corresponding to nitrile group
change their reactivity and make the nitile group non-reactive
toward anionic attack, such as hydride and alkyl anion. We also
Further we have studied the Anti-HIV-1 activity of our
compounds on C8166 cell line. The cellular toxicity of
compounds on C8166 was assessed by MTT colorimetric assay.
The inhibition effect of samples on acute HIV-1 infection was
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performed the control experiment to support the mechanism CDCl3): δ 7.71 (d, J = 8.7 Hz, 1H, Ar-H), 7.65-7.57 (m, 2H, Ar-H),
and observed that reaction proceed through anionic 7.46 (t, J = 7.3 Hz, 2H, Ar-H), 7.43-7.34 (m, 3H, Ar-H), 7.29 (ddd,
annulations in presence of n-butyllithium. We have also J = 8.5, 6.2, 1.6 Hz, 1H, Ar-H), 7.21 (d, J = 1.8 Hz, 1H, Ar-H), 7.13
explored the metal free, simple ring transformation method (d, J = 1.4 Hz, 1H, Ar-H), 3.38-3.16 (m, 4H, -CH2), 1.82 (q, J = 4.3
for synthesis of highly congested 2’-halo-[1,1’-biphenyl]-2- Hz, 4H, -CH2), 1.71-1.58 (m, 2H, -CH2); 13C-NMR (100 MHz,
carbonitriles (6a-s). Along with development of new synthetic CDCl3): δ 157.8, 146.8, 145.6, 139.8, 133.0, 131.0, 130.0, 128.7,
method, we also demonstrated the solvent dependent 127.3, 122.9, 121.7, 117.29, 116.5, 105.5, 53.5, 26.1, 24.0; IR:
fluorescence properties of 8n and found that polarity of 2928, 2853, 2217, 1591, 1557 cm-1; HRMS (m/z): [M+H]+ calcd
solvent plays an important role. Antiviral properties of some of for C24H22BrN2: 417.0961; found: 417.0949
these compounds were also studied and moderate activity was
obtained.
6b.
2''-bromo-5'-(pyrrolidin-1-yl)-[1,1':3',1''-terphenyl]-4'-
carbonitrile: Yield: 53%; 0.60 Rf (10% ethylacetate in hexane),
white crystalline solid; mp: 141-143oC; 1H-NMR (400 MHz,
CDCl3): δ 7.69 (d, J = 8.4 Hz, 1H, Ar-H), 7.60 (d, J = 8.4 Hz, 2H,
Ar-H), 7.47-7.41 (2H, Ar-H), 7.38 (t, J = 6.5 Hz, 3H, Ar-H), 7.28
(q, J = 2.8 Hz, 1H, Ar-H), 6.88 (s, 1H, Ar-H), 6.83 (s, 1H, Ar-H),
3.71 (q, J = 5.8 Hz, 4H, -CH2), 2.11-1.95 (m, 4H, -CH2); 13C-NMR
(100 MHz, CDCl3): δ 151.2, 147.7, 145.3, 140.7, 140.1, 132.8,
131.8, 129.7, 128.5, 127.2, 123.1, 119.4, 117.1, 111.9, 94.4,
50.3, 25.8; IR: 2959, 2854, 2218 (CN), 1592, 1557, cm-1; HRMS
(m/z): [M+H]+ calcd for C23H20BrN2: 403.0804; found: 403.0784.
Acknowledgements
The Authors are highly indebted to King Abdel-Aziz City for
Science and Technology (KACST) for financial support of this
work through the project number MS-35-38. RS thanks CSIR
for providing research fellowship. RP and S thank UGC for
research fellowship. RP thanks DST for providing financial
assistance to perform research. This work was supported by
grand from Shanghai Institute of Materia Medica, CAS
(CASIMM0320163020) to Prof. YT Zheng. Authors thank Mr. Kunal
for solving the crystal structure.
6c.
2''-bromo-5'-morpholino-[1,1':3',1''-terphenyl]-4'-
carbonitrile: Yield: 48%; 0.35 Rf (10% ethylacetate in hexane),
white crystalline solid; mp: 164-166oC; 1H-NMR (400 MHz,
CDCl3): δ 7.72 (d, J = 7.6 Hz, 1H, Ar-H), 7.61 (d, J = 7.6 Hz, 2H,
Ar-H), 7.54-7.35 (m, 5H, Ar-H), 7.35-7.28 (m, 1H, Ar-H), 7.23 (d,
J = 1.5 Hz, 2H, Ar-H), 3.94 (q, J = 3.1 Hz, 4H, -CH2), 3.44-3.21 (m,
4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 156.4, 147.1, 146.0,
139.5, 139.4, 133.1, 130.9, 130.2, 129.0, 128.7, 127.5, 127.3,
122.9, 122.8, 116.9, 116.4, 105.6, 67.0, 52.1; IR: 2960, 2853,
2217 (CN), 1591, 1556 cm-1; HRMS (m/z): [M+H]+ calcd for
C23H20BrN2O: 419.0754; found: 419.0749.
Experimental
General: Commercially available reagents from Sigma Aldrich,
Alfa Aesar and Spectrochem were used directly without any
further purification. 1H and 13C NMR spectra were recorded on
a 400 MHz NMR and 100 MHz NMR spectrometer and CDCl3
was used as solvent. Chemical shifts for all the compounds are
reported in parts per million shifts (δ-value) from considering
CDCl3 (δ 7.24 ppm for H and 77.00 ppm for 13C NMR) as an
1
internal standard. In 1H NMR signal patterns are reported as s,
singlet; d, doublet; dd, double doublet; t, triplet; m, multiplet;
bs, broad singlet and bm, broad multiplet. Coupling constant
(J) for protons are reported in hertz (Hz). Infrared (IR) spectra
of all the compounds was recorded on a Perkine Elmer AX-1
spectrophotometer and reported in wave number (cm-1).
HRMS reported are showing the peak for MH+.
6d.
2''-bromo-4-methyl-5'-(piperidin-1-yl)-[1,1':3',1''-
terphenyl]-4'-carbonitrile: Yield: 66%; 0.65 Rf (10%
ethylacetate in hexane), white crystalline solid; mp: 136-138oC;
1H-NMR (400 MHz, CDCl3): δ 7.69 (d, J = 7.6 Hz, 1H, Ar-H), 7.49
(d, J = 7.6 Hz, 2H, Ar-H), 7.43-7.32 (m, 2H, Ar-H), 7.31-7.21 (m,
3H, Ar-H), 7.18 (s, 1H, Ar-H), 7.11 (s, 1H, Ar-H), 3.33-3.16 (m,
4H, -CH2), 2.39 (s, 3H, -CH3), 1.80 (d, J = 3.8 Hz, 4H, -CH2), 1.61
(t, J = 5.7 Hz, 2H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 157.8,
146.7, 145.5, 139.9, 138.5, 136.8, 133.0, 131.0, 130.0, 129.6,
127.4, 127.1, 123.0, 121.6, 117.3, 116.3, 105.1, 53.5, 26.1,
24.0, 21.17; IR: 2934, 2853, 2216 (CN), 1590, 1552, cm-1; HRMS
(m/z): [M+H]+ calcd for C25H24BrN2: 431.1117; found: 431.1121.
General protocol for the synthesis of 2''-bromo-4-substituted-
5'-sec.amino-[1,1':3',1''-teraryl]-4'-carbonitriles (6a-o):
mixture of 6-aryl-4-sec.amino-2H-pyran-2-one-3-carbonitriles
(0.5 mmol) and 2′-bromoacetophenone 5a (0.6 mmol) in dry
A
4
DMSO (4.0 mL) in presence of powdered KOH (1.0 mmol) was
stirred at room temperature for 8 h. After completion of
reaction, mixture was poured onto crushed ice with constant
stirring, and then neutralized with 10% HCl. Thus obtained
precipitate was filtered and purified by silica gel column
chromatography using ethyl acetate:hexane (1:19) as an
eluent.
6e.
2''-bromo-4-methyl-5'-(pyrrolidin-1-yl)-[1,1':3',1''-
terphenyl]-4'-carbonitrile: Yield: 62%; 0.65 Rf (10%
ethylacetate in hexane), white crystalline solid; mp: 130-132oC;
1H-NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.4 Hz, 1H, Ar-H), 7.50
(d, J = 6.9 Hz, 2H, Ar-H), 7.46-7.32 (m, 3H, Ar-H), 7.32-7.19 (m,
2H, Ar-H), 6.87 (dd, J = 20.2, 14.9 Hz, 2H, Ar-H), 3.70 (d, J = 6.1
Hz, 4H, -CH2), 2.40 (s, 3H, -CH3), 2.03 (s, 4H, -CH2); 13C-NMR
(100 MHz, CDCl3): δ 151.4, 147.8, 145.4, 140.9, 138.5, 137.3,
132.9, 131.0, 129.8, 129.7, 127.4, 127.2, 123.3, 119.7, 117.2,
111.8, 94.3, 50.7, 26.0, 21.3; IR: 2925, 2866, 2206 (CN), 1592,
6a.
2''-Bromo-5'-(piperidin-1-yl)-[1,1':3',1''-terphenyl]-4'-
carbonitrile: Yield: 57%; 0.60 Rf (10% ethylacetate in hexane),
white crystalline solid; mp: 149-151oC; 1H-NMR (400 MHz,
6 | J. Name., 2012, 00, 1-3
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1549cm-1; HRMS (m/z): [M+H]+ calcd for C24H22BrN2: 417.0961; in hexane), white crystalline solid; mp: 158-160oC;1H-NMR
found: 417.0960.
(400 MHz, CDCl3): δ 8.07 (s, 1H, Ar-H), 7.99-7.81 (m, 3H, Ar-H),
7.78-7.69 (m, 2H, Ar-H), 7.53 (t, J = 4.2 Hz, 2H, Ar-H), 7.48-7.38
6f. 2''-bromo-4-methyl-5'-morpholino-[1,1':3',1''-terphenyl]- (m, 2H, Ar-H), 7.34 (s, 1H, Ar-H), 7.33-7.28 (m, 1H, Ar-H), 7.27
4'-carbonitrile: Yield: 48%; 0.40 Rf (10% ethylacetate in (s, 1H, Ar-H), 3.41-3.21 (m, 4H, -CH2), 1.84 (d, J = 4.6 Hz, 4H, -
hexane), white crystalline solid; mp: 153-155oC; 1H-NMR (400 CH2 ), 1.65 (t, J = 5.7 Hz, 2H, -CH2); 13C-NMR (100 MHz, CDCl3):
MHz, CDCl3): δ 7.72 (d, J = 8.4 Hz, 1H, Ar-H), 7.52 (d, J = 6.9 Hz, δ 157.9, 145.5, 133.0, 131.0, 130.0, 128.7, 128.3, 127.7, 127.4,
1H, Ar-H), 7.46-7.34 (m, 4H, Ar-H), 7.34-7.25 (m, 1H, Ar-H), 126.6, 126.6, 126.5, 125.1, 122.0, 116.7, 105.5, 53.5, 26.1,
7.25-7.20 (m, 2H, Ar-H), 7.12 (q, J = 3.1 Hz, 1H, Ar-H), 3.95 (t, J 24.0; IR: 2930, 2853, 2217 (CN), 1590, 1557 cm-1; HRMS (m/z):
= 13.0 Hz, 4H, -CH2), 3.40-3.25 (m, 4H, -CH2), 2.41 (s, 3H, -CH3); [M+H]+ calcd for C28H24BrN2: 467.1117; found: 467.1106.
13C-NMR (100 MHz, CDCl3): δ 156.5, 147.1, 146.1, 139.7, 139.0,
136.6, 133.2, 131.0, 130.3, 129.9, 127.6, 127.3, 123.0, 122.7, 6k.
2'-bromo-3-(piperidin-1-yl)-5-(thiophen-2-yl)-[1,1'-
117.2, 116.2, 105.4, 67.4, 52.2, 21.5; IR: 2956, 2851, 2216 (CN), biphenyl]-2-carbonitrile: Yield: 67%; 0.60 Rf (10% ethylacetate
1591, 1541 cm-1; HRMS (m/z): [M+H]+ calcd for C24H22BrN2O: in hexane), white crystalline solid; mp: 163-165oC; 1H-NMR
433.0910; found: 433.0927.
(400 MHz, CDCl3): δ 7.71 (d, J = 8.4 Hz, 1H, Ar-H), 7.48-7.33 (m,
4H, Ar-H), 7.30 (t, J = 6.5 Hz, 1H, Ar-H), 7.22 (s, 1H, Ar-H), 7.14
6g.
2''-bromo-4-methoxy-5'-(piperidin-1-yl)-[1,1':3',1''- (s, 1H, Ar-H), 7.11 (t, J = 4.2 Hz, 1H, Ar-H), 3.26 (dt, J = 14.8, 5.5
terphenyl]-4'-carbonitrile: Yield: 69%; 0.60 Rf (10% Hz, 4H, -CH2), 1.81 (d, J = 4.6 Hz, 4H, -CH2), 1.63 (t, J = 5.7 Hz,
ethylacetate in hexane), white crystalline solid; mp: 148-150oC; 2H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 158.0, 147.1, 142.8,
1H-NMR (400 MHz, CDCl3): δ 7.71 (d, J = 7.6 Hz, 1H, Ar-H), 7.59- 139.7, 138.6, 133.2, 131.0, 130.2, 128.4, 127.5, 126.8, 125.1,
7.50 (m, 2H, Ar-H), 7.44-7.34 (m, 2H, Ar-H), 7.30 (d, J = 9.2 Hz, 123.0, 120.2, 117.2, 115.0, 105.4, 53.4, 26.2, 24.1; IR: 2927,
1H, Ar-H), 7.18 (d, J = 1.5 Hz, 1H, Ar-H), 7.10 (d, J = 1.5 Hz, 1H, 2853, 2218 (CN), 1581, 1555 cm-1; HRMS (m/z): [M+H]+ calcd
Ar-H), 6.98 (d, J = 8.4 Hz, 2H, Ar-H), 3.86 (s, 3H, -OCH3), 3.33- for C22H20BrN2S: 423.0525; found: 423.0529.
3.19 (m, 4H, -CH2), 1.81 (s, 4H, -CH2), 1.63 (t, J = 5.7 Hz, 2H, -
CH2); 13C-NMR (100 MHz, CDCl3): δ 160.2, 158.0, 146.8, 145.3, 6l.
2'-bromo-3-(pyrrolidin-1-yl)-5-(thiophen-2-yl)-[1,1'-
140.0, 133.1, 132.2, 131.1, 130.1, 129.0, 128.5, 127.5, 123.1, biphenyl]-2-carbonitrile: Yield: 64%; 0.60 Rf (10% ethylacetate
121.4, 116.1, 114.5, 104.9, 55.5, 53.6, 26.3, 24.2; IR: 2926, in hexane), white crystalline solid; mp: 154-156oC; 1H-NMR
2853, 2216 (CN), 1590, 1557 cm-1; HRMS (m/z): [M+H]+ calcd (400 MHz, CDCl3): δ 7.69 (d, J = 8.4 Hz, 1H, Ar-H), 7.44-7.32 (m,
for C25H24BrN2O: 447.1067; found: 447.1068.
4H, Ar-H), 7.32-7.24 (m, 1H, Ar-H), 7.09 (q, J = 3.6 Hz, 1H, Ar-
H), 6.91 (s, 1H, Ar-H), 6.85 (s, 1H, Ar-H), 3.70 (d, J = 6.1 Hz, 4H,
6h.
2''-bromo-4-methoxy-5'-(pyrrolidin-1-yl)-[1,1':3',1''- -CH2), 2.03 (s, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 151.2,
terphenyl]-4'-carbonitrile: Yield: 63%; 0.60 Rf (10% 147.9, 143.1, 140.5, 138.1, 132.8, 130.8, 129.8, 128.1, 127.3,
ethylacetate in hexane), white crystalline solid; mp: 137-139oC; 126.3, 124.7, 123.1, 119.3, 115.6, 110.2, 94.4, 50.3, 25.8; IR:
1H-NMR (400 MHz, CDCl3): δ 7.69 (d, J = 7.6 Hz, 1H, Ar-H), 7.59- 2958, 2855, 2206 (CN), 1593, 1552 cm-1; HRMS (m/z): [M+H]+
7.52 (m, 2H, Ar-H), 7.48 (s, 1H, Ar-H), 7.39 (d, J = 6.9 Hz, 2H, Ar- calcd for C21H18BrN2S: 409.0369; found: 409.0390.
H), 7.32-7.23 (1H, Ar-H), 6.97 (d, J = 8.4 Hz, 1H, Ar-H), 6.81 (q, J
= 8.6 Hz,2H, Ar-H), 3.85 (s, 3H, -OCH3), 3.71 (d, J = 4.6 Hz, 4H, - 6m.
3-(2-bromophenyl)-1-(piperidin-1-yl)-9,10-
CH2), 2.04 (d, J = 5.3 Hz, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): dihydrophenanthrene-2-carbonitrile: Yield: 61%; 0.60 Rf (10%
δ 157.9, 147.0, 144.3, 139.6, 138.6, 133.1, 132.0, 128.9, 128.8, ethylacetate in hexane), white crystalline solid; mp: 137-139
1
122.9, 121.5, 121.3, 117.1, 116.4, 116.1, 105.8, 57.9, 53.5, oC; H-NMR (400 MHz, CDCl3): δ 7.74-7.66 (m, 2H, Ar-H), 7.45
26.1; IR: 2923, 2852, 2206 (CN), 1596, 1549, cm-1; HRMS (m/z): (s, 1H, Ar-H), 7.40 (t, J = 6.5 Hz, 2H, Ar-H), 7.30 (dd, J = 9.5, 2.7
[M+H]+ calcd for C24H22BrN2O: 433.0910; found: 433.0918.
Hz, 4H, Ar-H), 3.27 (s, 4H, -CH2), 3.04-2.84 (m, 4H, -CH2), 1.83-
1.60 (m, 6H,-CH2); 13C-NMR (100 MHz, CDCl3): δ 154.1, 137.8,
6i. 2''-bromo-4-chloro-5'-morpholino-[1,1':3',1''-terphenyl]- 134.8, 133.7, 133.0, 131.1, 129.9, 128.7, 127.9, 127.4, 127.1,
4'-carbonitrile: Yield: 54%; 0.25 Rf (10% ethylacetate in 124.7, 121.2, 107.7, 52.1, 28.5, 26.8, 24.1, 23.3; IR: 2924, 2853,
1
hexane), white crystalline solid; mp: 186-188oC; H-NMR (400 2219 (CN), 1600, 1540 cm-1; HRMS (m/z): [M+H]+ calcd for
MHz, CDCl3): δ 7.72 (d, J = 7.6 Hz, 1H, Ar-H), 7.55 (dd, J = 6.5, C26H24BrN2: 443.1117; found: 443.1127.
1.9 Hz, 2H, Ar-H), 7.49-7.40 (m, 3H, Ar-H), 7.39-7.28 (m, 2H, Ar-
H), 7.18 (s, 2H, Ar-H), 3.94 (t, J = 3.8 Hz, 4H, -CH2), 3.41-3.24 6n.
3-(2-bromophenyl)-7-methoxy-1-(piperidin-1-yl)-9,10
(m, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 156.5, 147.2, dihydrophenanthrene-2-carbonitrile: Yield: 58%; 0.60 Rf (10%
144.7, 139.3, 137.8, 134.9, 133.1, 130.9, 130.3, 129.2, 128.5, ethylacetate in hexane), white crystalline solid; mp: 133-135oC;
127.5, 122.8, 122.6, 116.8, 116.1, 105.9, 66.9, 52.1; IR: 2961, 1H-NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.4 Hz, 1H, Ar-H), 7.62
2854, 2218 (CN), 1593, 1553 cm-1; HRMS (m/z): [M+Na]+ calcd (d, J = 8.4 Hz, 1H, Ar-H), 7.40 (dd, J = 8.0, 5.7 Hz, 3H, Ar-H),
for C23H19BrClN2O: 475.0183; found: 475.0249.
7.31-7.27 (m, 1H, Ar-H), 6.82 (d, J = 9.2 Hz, 2H, Ar-H), 3.85 (s,
3H, -OCH3), 3.26 (s, bs, 4H, -CH2), 3.04-2.77 (4H, -CH2), 1.73-
2'-bromo-5-(naphthalen-2-yl)-3-(piperidin-1-yl)-[1,1'- 1.55 (m, 6H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 160.0, 154.0,
6j.
biphenyl]-2-carbonitrile: Yield: 58%; 0.60 Rf (10% ethylacetate 144.4, 140.0, 139.7, 139.5, 133.9, 133.0, 131.2, 129.8, 127.4,
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126.6, 126.2, 123.3, 121.0, 118.2, 113.2, 112.5, 106.9, 55.3, 6r.
2'-fluoro-3-(piperidin-1-yl)-5-(thiophen-2-yl)-[1,1'-
52.1, 28.9, 26.8, 24.1, 23.3; IR: 2926, 2850, 2219 (CN), 1602, biphenyl]-2-carbonitrile: Yield: 73%; 0.65 Rf (10% ethylacetate
1543 cm-1; HRMS (m/z): [M+H]+ calcd for C27H26BrN2O: in hexane), white crystalline solid; mp: 181-183oC; 1H-NMR
473.1223; found: 473.1231.
(400 MHz, CDCl3): δ 7.48-7.34 (m, 4H, Ar-H), 7.27 (d, J = 6.1 Hz,
1H, Ar-H), 7.24-7.17 (m, 3H, Ar-H), 7.11 (t, J = 3.8 Hz, 1H, Ar-H),
6o.
3-(2-bromophenyl)-7-methoxy-1-(pyrrolidin-1-yl)-9,10- 3.26 (t, J = 5.3 Hz, 4H, -CH2), 1.81 (d, J = 4.6 Hz, 4H, -CH2), 1.64
dihydrophenanthrene-2-carbonitrile: Yield: 56%; 0.60 Rf (10% (d, J = 5.3 Hz, 2H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 158.2,
ethylacetate in hexane), white crystalline solid; mp: 130-132oC; 142.7, 141.9, 138.7, 131.2, 130.7, 130.6, 128.3, 126.7, 125.0,
1H-NMR (400 MHz, CDCl3): δ 7.67 (dd, J = 33.6, 8.4 Hz, 2H, Ar- 124.2, 120.5, 117.4, 116.2, 116.0, 115.0, 105.4, 53.4, 26.1,
H), 7.40 (q, J = 1.5 Hz, 3H, Ar-H), 7.31-7.23 (m, 1H, Ar-H), 6.83 24.0; IR: 2934, 2853, 2216 (CN), 1591, 1556, cm-1; HRMS (m/z):
(d, J = 9.9 Hz, 2H, Ar-H), 3.84 (s, 3H, -OCH3), 3.44 (d, J = 6.9 Hz, [M+H]+ calcd for C22H20FN2S: 363.1226; found: 363.1234.
4H, -CH2), 2.87 (d, J = 3.8 Hz, 4H, -CH2), 2.04 (d, J = 6.1 Hz, 4H, -
CH2); 13C-NMR (100 MHz, CDCl3): δ 150.6, 144.5, 139.8, 139.5, 6s.
2'-chloro-3-(piperidin-1-yl)-5-(thiophen-2-yl)-[1,1'-
137.9, 135.8, 133.7, 133.0, 131.2, 129.9, 128.7, 128.0, 127.4, biphenyl]-2-carbonitrile: Yield: 70%; 0.65 Rf (10% ethylacetate
127.1, 124.7, 123.2, 121.9, 117.6, 109.0, 55.9, 51.4, 28.5, 26.3, in hexane), white crystalline solid; mp: 166-168oC; 1H-NMR
23.6; IR: 2929, 2842, 2217 (CN), 1582, 1539 cm-1; HRMS (m/z): (400 MHz, CDCl3): δ 7.59-7.46 (m, 1H, Ar-H), 7.43-7.35 (m, 5H,
[M+H]+ calcd for C26H24BrN2O: 459.1067; found: 459.1066.
Ar-H), 7.22 (d, J = 0.9 Hz, 1H, Ar-H), 7.16 (d, J = 0.9 Hz, 1H, Ar-
H), 7.11 (td, J = 4.4, 1.1 Hz, 1H, Ar-H), 3.26 (t, J = 6.0 Hz, 4H, -
Synthetic protocol for the synthesis of 2''-fluoro/chloro-4- CH2), 1.90-1.73 (m, 4H, -CH2), 1.71-1.59 (m, 2H, -CH2); 13C-NMR
substituted-5'-sec.amino-[1,1':3',1''-teraryl]-4'-carbonitriles
(100 MHz, CDCl3): δ 158.0, 145.3, 142.7, 138.6, 137.6, 133.0,
131.0, 129.9, 129.9, 128.3, 126.8, 125.0, 120.2, 117.2, 114.9,
(6p-s):
A
mixture
of
6-aryl-4-sec.amino-2H-pyran-2-one-3- 105.4, 53.4, 26.1, 24.0; IR: 2931, 2853, 2216 (CN), 1591, 1558
carbonitriles 4 (0.5 mmol) and 2′-fluoro/chloro-acetophenone cm-1; HRMS (m/z): [M+H]+ calcd for C22H20FN2S: 379.1030;
(0.6 mmol) in dry DMSO (4.0 mL) in presence of powdered found: 379.1023.
KOH (1.0 mmol) was stirred at room temperature for 10 h.
After completion of reaction, mixture was poured onto ice General protocol for the synthesis of 1-sec.amino-3-aryl-9H-
with constant stirring then neutralized with 10%HCl. The fluoren-9-ones (8a-o) with n-BuLi:
precipitate was filtered and purified by silica gel column To the vacuum dried round bottom flask 2''-bromo-4-aryl-5'-
chromatography with ethylacetate / hexane (1:19) as eluent.
sec- amino-[1,1':3',1''-teraryl]-4'-carbonitriles
taken under nitrogen atmosphere followed by addition of dry
2''-fluoro-4-methyl-5'-(piperidin-1-yl)-[1,1':3',1''- THF (1.0 mL). The solution of
was cooled to -78 oC and n-BuLi
6 (0.3 mmol) was
6p.
6
terphenyl]-4'-carbonitrile: Yield: 67%; 0.65 Rf (10% in THF (1.5 ml, 0.9 mmol) was added drop-wise to the solution.
ethylacetate in hexane), white crystalline solid; mp: 157-159oC; After complete addition of n-BuLi, dry ice bath was removed
1H-NMR (400 MHz, CDCl3): δ 7.50 (dd, J = 8.0, 1.9 Hz, 2H, Ar-H), and the mixture was further stirred at room temperature for 3
7.46-7.37 (m, 2H, Ar-H), 7.32-7.24 (m, 3H, Ar-H), 7.24-7.16 (m, hours. After completion, the reaction was quenched with
3H, Ar-H), 3.25 (t, J = 4.2 Hz, 4H, -CH2), 2.41 (s, 3H, -CH3), 1.82 saturated NH4Cl (3.0 mL), extracted with ethyl acetate (3 times
(s, 4H, -CH2), 1.63 (d, J = 4.6 Hz, 2H, -CH2); 13C-NMR (100 MHz, in 10 mL), and organic layer was dried over sodium sulphate.
CDCl3): δ 158.2, 145.8, 141.6, 138.5, 136.8, 131.7, 130.8, 130.0, The solvent was evaporated to obtain the crude product,
129.2, 127.5, 126.6, 124.6, 122.3, 117.5, 116.9, 116.0, 105.2, which was purified by silica gel column chromatography using
53.5, 26.1, 24.0; IR: 2930, 2854, 2217 (CN), 1592, 1554 cm-1; DCM/hexane (3:7) as eluent.
HRMS (m/z): [M+H]+ calcd for C25H24FN2: 371.1918; found:
371.1880.
Synthesis of 1-(piperidin-1-yl)-3-(p-tolyl)-9H-fluoren-9-one
with LiAlH4:
6q.
2''-chloro-4-methyl-5'-(piperidin-1-yl)-[1,1':3',1''- To a nitrogen flushed 10 ml pressure vial 2''-bromo-4-methyl-
terphenyl]-4'-carbonitrile: Yield: 63%; 0.65 Rf (10% 5'-(piperidin-1-yl)-[1,1':3',1''-terphenyl]-4'-carbonitrile 6d (0.3
ethylacetate in hexane), white crystalline solid; mp: 140-142oC; mmol) was dissolved in THF (1.0 mL) and cooled to -20 oC.
1H-NMR (400 MHz, CDCl3): δ 7.53-7.46 (m, 3H, Ar-H), 7.42-7.33 Then LiAlH4 (0.9 mmol) was added to the solution at the same
(m, 3H, Ar-H), 7.25 (d, J = 7.3 Hz, 2H, Ar-H), 7.19 (d, J = 1.8 Hz, temperature and sealed the tube. Then, reaction was heated
1H, Ar-H), 7.14-7.10 (1H, Ar-H), 3.33-3.17 (m, 4H, -CH2), 2.42- at 100 oC till completion of reaction. After completion, reaction
2.36 (3H, -CH3), 1.88-1.74 (m, 4H, -CH2), 1.62 (q, J = 5.8 Hz, 2H, mixture was diluted with ether (30 mL) and organic layer was
-CH2); 13C-NMR (100 MHz, CDCl3): δ 157.9, 145.6, 145.1, 138.5, washed with 10% NaOH solution (15 mLx2) and water (15
137.9, 136.8, 133.0, 131.1, 129.9, 129.8, 129.6, 127.0, 121.6, mLx2). The reaction mixture was dried over Na2SO4 and crude
117.3, 116.3, 105.3, 53.5, 26.1, 24.0, 21.2; IR: 2928, 2854, 2216 was purified by silica gel column chromatography using
(CN), 1591, 1554 cm-1; HRMS (m/z): [M+H]+ calcd for DCM/hexane (3:7) as eluent.
C25H24ClN2: 387.1623; found: 387.1618.
8a. 3-phenyl-1-(piperidin-1-yl)-9H-fluoren-9-one: Yield: 64%;
0.45 Rf (10% ethylacetate in hexane), yellow solid; mp: 114-
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116oC; H-NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.2 Hz, 1H, Ar- 8f. 1-morpholino-3-(p-tolyl)-9H-fluoren-9-one: Yield: 65%;
H), 7.52 (d, J = 8.2 Hz, 2H, Ar-H), 7.42-7.29 (4H, Ar-H), 7.19 (q, J 0.20 Rf (10% ethylacetate in hexane), yellow solid; mp: 121-
1
= 7.2 Hz, 2H, Ar-H), 7.13 (s, 1H, Ar-H), 7.05 (s, 1H, Ar-H), 3.21 123oC; H-NMR (400 MHz, CDCl3): δ 7.61 (d, J = 7.8 Hz, 2H, Ar-
(td, J = 12.7, 5.6 Hz, 4H, -CH2), 1.81-1.64 (m, 4H, -CH2), 1.61- H), 7.55 (d, J = 10.5 Hz, 2H, Ar-H), 7.49-7.34 (m, 4H, Ar-H), 7.22
1.46 (m, 2H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 191.2, 157.8, (s, 1H, Ar-H), 7.00 (s, 1H, Ar-H), 3.98 (t, J = 4.4 Hz, 4H, -CH2),
146.7, 145.6, 139.8, 133.0, 130.0, 128.9, 128.5, 127.4, 127.3, 3.39-3.35 (4H, -CH2), 2.43 (s, 3H, -CH3); 13C-NMR (100 MHz,
122.9, 121.8, 117.2, 116.5, 105.4, 53.4, 26.1, 24.0; IR: 2927, CDCl3) : δ 191.1, 156.5, 151.8, 141.8, 133.6, 133.1, 129.7,
2854, 1691 (CO), 1595, 1557 cm-1; HRMS (m/z): [M+H]+ calcd 128.3, 127.0, 125.0, 123.4, 121.1, 119.9, 114.9, 112.2, 110.9,
for C24H22NO: 340.1696; found: 340.1688.
105.5, 67.0, 52.2, 21.2; IR: 2955, 2854, 1690 (CO), 1604, 1556
cm-1; HRMS (m/z): [M+H]+ calcd for C24H22NO2: 356.1645;
8b. 3-phenyl-1-(pyrrolidin-1-yl)-9H-fluoren-9-one: Yield:61%; found: 356.1642.
0.43 Rf (10% ethylacetate in hexane), yellow solid; mp: 107-
1
109oC; H-NMR(400 MHz, CDCl3): δ 7.70 (d, J = 8.4 Hz, 1H, Ar- 8g. 3-(4-methoxyphenyl)-1-(piperidin-1-yl)-9H-fluoren-9-one:
H), 7.64-7.57 (m, 2H, Ar-H), 7.45 (td, J = 7.2, 1.5 Hz, 2H, Ar-H), Yield: 61%; 0.40 Rf (10% ethylacetate in hexane), yellow solid;
7.42-7.36 (m, 3H, Ar-H), 7.32-7.27 (m, 1H, Ar-H), 6.88 (s, 1H, mp: 115-117oC; 1H-NMR (400 MHz, CDCl3): δ 7.71 (d, J = 6.9 Hz,
Ar-H), 6.83 (d, J = 1.5 Hz, 1H, Ar-H), 3.71 (q, J = 5.8 Hz, 4H, - 1H, Ar-H), 7.62-7.53 (m, 2H, Ar-H), 7.47 (d, J = 8.4 Hz, 1H, Ar-
CH2), 2.12-1.95 (m, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ H), 7.44-7.34 (m, 2H, Ar-H), 7.29 (dd, J = 8.4, 6.9 Hz, 1H, Ar-H),
191.9, 157.9, 151.2, 147.8, 145.4, 140.2, 132.8, 130.9, 128.8, 7.17 (d, J = 6.9 Hz, 1H, Ar-H), 7.09 (d, J = 3.8 Hz, 1H, Ar-H),
128.3, 127.3, 123.1, 119.4, 117.2, 111.9, 105.3, 94.5, 53.3, 7.02-6.94 (1H, Ar-H), 3.86 (s, 3H, -OCH3), 3.26 (t, J = 6.5 Hz,
25.8; IR: 2925, 2854, 1684 (CO), 1593, 1553 cm-1; HRMS (m/z): 4H,-CH2), 1.81 (s, 4H, -CH2), 1.67-1.60 (2H, -CH2); 13C-NMR (100
[M+H]+ calcd for C23H20NO: 326.1539; found: 326.1536.
MHz, CDCl3): δ 191.0, 157.9, 152.8, 147.0, 142.7, 139.6, 138.6,
129.1, 127.5, 126.7, 126.3, 123.3, 119.8, 117.2, 115.6, 109.9,
8c. 1-morpholino-3-phenyl-9H-fluoren-9-one: Yield: 66%; 0.15 105.3, 56.5, 53.4, 26.1, 24,3; IR: 2929, 2853, 1688 (CO), 1595,
Rf (10% ethylacetate in hexane), yellow solid; mp: 134-136oC; 1555 cm-1; HRMS (m/z): [M+H]+ calcd for C25H24NO2: 369.1961;
1H-NMR(400 MHz, CDCl3): δ 7.69-7.59 (m, 3H, Ar-H), 7.56 (d, J found: 369.1964.
= 6.9 Hz, 1H, Ar-H), 7.53-7.42 (m, 4H, Ar-H), 7.31 (t, J = 6.9 Hz,
2H, Ar-H), 6.97 (s, 1H, Ar-H), 3.99 (t, J = 4.6 Hz, 4H, -CH2), 3.38 8h.
3-(4-methoxyphenyl)-1-(pyrrolidin-1-yl)-9H-fluoren-9-
(t, J = 4.6 Hz, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 191.5, one: Yield: 59%; 0.38 Rf (10% ethylacetate in hexane), yellow
156.4, 151.8, 149.3, 143.3, 141.8, 135.3, 133.1, 130.9, 129.8, solid; mp: 103-105oC; H-NMR (400 MHz, CDCl3) : δ 7.78-7.48
1
127.0, 123.4, 121.0, 114.9, 112.2, 110.9, 105.4, 67.0, 52.0; IR: (m, 4H, Ar-H), 7.48-7.34 (m, 1H, Ar-H), 7.29 (t, J = 7.2 Hz, 1H,
2923, 2854, 1690 (CO), 1603, 1556 cm-1; HRMS (m/z): [M+H]+ Ar-H), 7.10 (d, J = 1.5 Hz, 1H, Ar-H), 6.98 (dd, J = 13.4, 8.8 Hz,
calcd for C23H20NO2: 342.1489; found: 342.1499.
2H, Ar-H), 6.82 (d, J = 15.3 Hz, 1H, Ar-H), 3.93-3.80 (s, 3H, -
OCH3), 3.76-3.58 (m, 4H, -CH2), 2.10-1.94 (m, 4H, -CH2); 13C-
8d. 1-(piperidin-1-yl)-3-(p-tolyl)-9H-fluoren-9-one: Yield: 67%; NMR (100 MHz, CDCl3): δ 191.0, 157.6, 152.6, 147.7, 142.6,
0.47 Rf (10% ethylacetate in hexane), yellow solid; mp: 102- 138.6, 133.1, 130.9, 128.4, 127.5, 126.7, 123.0, 119.9, 119.7,
1
104oC; H-NMR (400 MHz, CDCl3): δ 7.62 (d, J = 6.9 Hz, 1H, Ar- 114.9, 109.8, 96.8, 57.5, 53.5, 26.1; IR: 2925, 2854, 1680 (CO),
H), 7.54 (dd, J = 7.1, 5.5 Hz, 3H, Ar-H), 7.43 (t, J = 8.0 Hz, 1H, 1607, 1546 cm-1; HRMS (m/z): [M+H]+ calcd for C24H22NO2:
Ar-H), 7.27 (dd, J = 8.0, 5.7 Hz, 3H, Ar-H), 7.23 (d, J = 1.5 Hz, 1H, 356.1645; found: 356.1640.
Ar-H), 6.97 (d, J = 1.5 Hz, 1H, Ar-H), 3.33 (t, J = 5.3 Hz, 4H, -
CH2), 2.42 (s, 3H, -CH3), 1.93-1.77 (m, 4H, -CH2), 1.73-1.56 (m, 8i. 3-(4-chlorophenyl)-1-morpholino-9H-fluoren-9-one: Yield:
2H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 191.2, 152.6, 149.1, 49%; 0.14 Rf (10% ethylacetate in hexane), yellow solid; mp:
147.4, 143.0, 138.4, 137.7, 135.5, 133.2, 129.9, 128.2, 127.0, 148-150oC; 1H-NMR (400 MHz, CDCl3): δ 7.62 (d, J = 6.9 Hz, 1H,
126.3, 124.7, 123.2, 120.0, 117.5, 111.2, 109.9, 52.6, 26.1, Ar-H), 7.60-7.51 (m, 3H, Ar-H), 7.51-7.42 (m, 3H, Ar-H), 7.35-
24.2, 21.2; IR: 2924, 2854, 1684 (CO), 1593, 1552 cm-1; HRMS 7.27 (m, 1H, Ar-H), 7.16 (d, J = 11.4 Hz, 1H, Ar-H), 6.92 (s, 1H,
(m/z): [M+H]+ calcd for C25H24NO: 354.1852; found: 354.1863.
Ar-H), 3.97 (td, J = 9.5, 4.8 Hz, 4H, -CH2), 3.35 (dt, J = 24.4, 4.6
Hz, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 191.4, 151.7,
8e. 1-(pyrrolidin-1-yl)-3-(p-tolyl)-9H-fluoren-9-one: Yield: 147.9, 142.8, 138.8, 135.1, 134.7, 133.7, 129.3, 129.1, 128.5,
62%; 0.45 Rf (10% ethylacetate in hexane), yellow solid; mp: 123.5, 120.4, 119.9, 116.7, 112.0, 67.0, 51.5; IR: 2924, 2855,
1
95-97oC; H-NMR (400 MHz, CDCl3): δ 7.71 (d, J = 7.6 Hz, 1H, 1690 (CO), 1604, 1554 cm-1; HRMS (m/z): [M+H]+ calcd for
Ar-H), 7.53 (d, J = 7.6 Hz, 2H, Ar-H), 7.39 (dd, J = 16.8, 6.1 Hz, C23H19ClNO2: 376.1099; found: 376.1103.
3H, Ar-H), 7.35-7.27 (m, 2H, Ar-H), 6.89 (dd, J = 20.2, 14.9 Hz,
2H, Ar-H), 3.72 (d, J = 5.3 Hz, 4H, -CH2), 2.42 (s, 3H, -CH3), 2.05 8j.
3-(naphthalen-2-yl)-1-(piperidin-1-yl)-9H-fluoren-9-one:
(s, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 190.9, 152.7, 147.7, Yield: 58%; 0.42 Rf (10% ethylacetate in hexane), yellow solid;
143.7, 142.6, 141.4, 135.5, 133.3, 129.1, 128.3, 126.3, 124.8, mp: 124-126oC; 1H-NMR (400 MHz, CDCl3): δ 8.00 (s, 1H, Ar-H),
123.1, 119.9, 119.8, 115.6, 109.9, 52.6, 26.1, 24.3; IR: 2926, 7.87-7.73 (m, 4H, Ar-H), 7.69-7.62 (m, 1H, Ar-H), 7.57-7.52 (1H,
2854, 1690 (CO), 1604, 1555 cm-1; HRMS (m/z): [M+Na]+ calcd Ar-H), 7.49-7.39 (m, 3H, Ar-H), 7.37-7.30 (m, 1H, Ar-H), 7.19 (q,
for C24H22NO: 362.1521; found: 362.1539.
J = 7.1 Hz, 1H, Ar-H), 7.00 (s, 1H, Ar-H), 3.26 (t, J = 5.3 Hz, 4H, -
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CH2), 1.84-1.71 (m, 4H, -CH2), 1.63-1.49 (m, 2H, -CH2); 13C-NMR
(100 MHz, CDCl3): δ 191.3, 152.6, 148.7, 147.5, 142.9, 137.9, 8o.
3-methoxy-7-(pyrrolidin-1-yl)-5H-indeno[2,1-
135.4, 133.4, 133.3, 133.1, 128.9, 128.7, 128.5, 128.3, 127.6, b]phenanthren-8(6H)-one: Yield: 56%; 0.47 Rf (10%
127.4, 126.5, 126.4, 126.1, 125.1, 123.2, 119.8, 119.7, 117.7, ethylacetate in hexane), yellow solid; mp: 96-98oC; 1H-NMR
111.5, 53.4, 26.0, 24.2; IR: 2934, 2853, 1689 (CO), 1604, 1556 (400 MHz, CDCl3): δ 7.73 (d, J = 9.2 Hz, 1H, Ar-H), 7.57 (q, J =
cm-1; HRMS (m/z): [M+H]+ calcd for C28H24NO: 390.1852; 8.4 Hz, 3H, Ar-H), 7.48-7.39 (m, 1H, Ar-H), 7.27 (d, J = 8.4 Hz,
found: 390.1874.
2H, Ar-H), 6.95-6.77 (m, 2H, Ar-H), 3.87 (s, 3H, -OCH3), 3.44-
3.25 (m, 4H, -CH2), 2.85 (dt, J = 27.5, 4.0 Hz, 4H, -CH2), 2.20-
1-(piperidin-1-yl)-3-(thiophen-2-yl)-9H-fluoren-9-one: 1.97 (m, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 192.2, 154.1,
8k.
Yield: 67%; 0.45 Rf (10% ethylacetate in hexane), yellow solid; 150.6, 144.5, 139.5, 137.9, 133.0, 131.2, 129.9, 128.7, 128.0,
mp: 128-130oC; 1H-NMR (400 MHz, CDCl3): δ 7.62 (d, J = 6.9 Hz, 127.4, 124.7, 123.2, 121.8, 119.3, 117.7, 107.7, 56.2, 52.1,
1H, Ar-H), 7.55 (d, J = 7.6 Hz, 1H, Ar-H), 7.49-7.41 (m, 2H, Ar- 28.5, 26.8, 26.3; IR: 2929, 2841, 1698 (CO), 1602, 1543 cm-1;
H), 7.40-7.33 (1H, Ar-H), 7.33-7.26 (m, 2H, Ar-H), 7.17-7.07 (m, HRMS (m/z): [M+H]+ calcd for C26H24NO2: 382.1802; found:
1H, Ar-H), 7.03 (s, 1H, Ar-H), 3.32 (t, J = 5.3 Hz, 4H, -CH2), 1.94- 382.1818.
1.77 (m, 4H, -CH2), 1.65 (q, J = 5.8 Hz, 2H, -CH2); 13C-NMR (100
MHz, CDCl3): δ 191.3, 152.6, 147.5, 142.9, 137.9, 135.4, 133.3, 9. Synthesis of 4-methyl-5'-(piperidin-1-yl)-[1,1':3',1''-
128.9, 128.5, 128.3, 127.7, 126.1, 125.1, 123.2, 119.7, 117.7, terphenyl]-4'-carbonitrile: A mixture of 4-(piperidin-1-yl)-6-
111.5, 52.7, 26.0, 24.2; IR: 2926, 2853, 1689 (CO), 1603, 1555 tolyl-2H-pyran-2-one-3-carbonitriles
(0.5
mmol)
and
cm-1; HRMS (m/z): [M+H]+ calcd for C22H20NOS: 346.1260; acetophenone (0.6 mmol) in presence of powdered KOH (1.0
found: 346.1263.
8l.
mmol) and dry DMSO (4.0 mL) was stirred at room
temperature for 8 h. After completion, mixture was poured
1-(pyrrolidin-1-yl)-3-(thiophen-2-yl)-9H-fluoren-9-one: onto crushed ice with constant stirring, and then neutralized
Yield: 64%; 0.44 Rf (10% ethylacetate in hexane), yellow solid; with 10% HCl. Thus obtained precipitate was filtered, washed
mp: 120-122oC; 1H-NMR (400 MHz, CDCl3): δ 7.76-7.63 (m, 1H, with water, dried and purified by silica gel column
Ar-H), 7.44-7.32 (m, 4H, Ar-H), 7.28 (td, J = 7.8, 2.8 Hz, 1H, Ar- chromatography using ethyl acetate:hexane (1:19) as an
H), 7.09 (t, J = 4.2 Hz, 1H, Ar-H), 6.91 (d, J = 1.5 Hz, 1H, Ar-H), eluent.
6.86 (d, J = 1.5 Hz, 1H, Ar-H), 3.80-3.60 (m, 4H, -CH2), 2.12-1.94 yield: 75%; 0.7 Rf (10% ethyl acetate in hexane), white solid;
(m, 4H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 190.6, 148.2, mp: 102-104oC; 1H-NMR (400 MHz, CDCl3): δ 7.56 (d, J = 8.2 Hz,
147.2, 143.9, 142.2, 140.6, 135.9, 132.8, 128.9, 128.1, 126.0, 2H, Ar-H), 7.41-7.50 (m, 5H, Ar-H), 7.25 (d, J = 7.8 Hz, 2H, Ar-
124.4, 122.9, 119.6, 115.5, 113.1, 107.4, 51.8, 25.8; IR: 2924, H), 7.20 (d, J = 1.4 Hz, 1H, Ar-H), 7.16 (d, J = 1.8 Hz, 1H, Ar-H),
2854, 1681 (CO), 1606, 1549 cm-1; HRMS (m/z): [M+H]+ calcd 3.24 (t, J = 5.0 Hz, 4H, -CH2), 2.39 (s, 3H, CH3), 1.78-1.84 (m, 4H,
for C21H18NOS: 332.1104; found: 332.1099.
-CH2), 1.58-1.64 (m, 2H, -CH2); 13C-NMR (100 MHz, CDCl3): δ
155.8, 145.0, 143.0, 136.2, 135.7, 134.1, 126.8, 126.1, 125.6,
8m. 7-(piperidin-1-yl)-5H-indeno[2,1-b]phenanthren-8(6H)- 124.3, 118.5, 115.3, 113.1, 101.1, 50.8, 25.0, 23.3, 21.2; IR:
one: Yield: 60%; 0.52 Rf (10% ethylacetate in hexane), yellow 2927, 2855, 2215 (CN), 1594, 1553 cm-1; HRMS (m/z): [M+H]+
solid; mp: 102-104oC; 1H-NMR (400 MHz, CDCl3): δ 7.75-7.64 calcd for C25H25N2: 353.2012; found: 353.2031.
(m, 2H, Ar-H), 7.45 (s, 1H, Ar-H), 7.43-7.36 (m, 2H, Ar-H), 7.34-
7.26 (m, 4H, Ar-H), 3.27 (s, 4H, -CH2), 3.06-2.80 (m, 4H, -CH2), 10. Synthesis of 3-(piperidin-1-yl)-5-(thiophen-2-yl)-[1,1'-
1.83-1.59 (6H, -CH2); 13C-NMR (100 MHz, CDCl3): δ 192.2, biphenyl]-2-carbonitrile-2'-d:
154.1, 144.5, 143.5, 139.5, 137.9, 135.8, 133.7, 133.0, 131.2, A 10 ml dry round bottom flask 2''-bromo-3-(piperidin-1-yl)-5-
129.8, 128.7, 127.4, 124.7, 123.2, 121.8, 119.3, 117.6, 108.9, (thiophen-2-yl)-[1,1'-biphenyl]-2-carbonitrile 6k (0.3 mmol)
51.5, 28.5, 26.8, 26.3, 23.3; IR: 2929, 2851, 1696 (CO), 1599, was taken under nitrogen atmosphere and dissolved in dry THF
1541 cm-1; HRMS (m/z): [M+H]+ calcd for C26H24NO: 366.1852; (1.0 mL). The solution of 6k was cooled to -78 oC and n-BuLi in
found: 366.1868.
THF (1.5 ml, 0.9 mmol) was added drop-wise. After complete
addition of n-BuLi, dry ice bath was removed and mixture was
8n.
3-methoxy-7-(piperidin-1-yl)-5H-indeno[2,1- stirred at room temperature for 30 minutes. Then reaction
b]phenanthren-8(6H)-one: Yield: 55%; 0.48 Rf (10% mixture was quenched with D2O (0.5 mL) and stirring was
1
ethylacetate in hexane), yellow solid; mp: 100-102oC; H-NMR continued for further half hour. Reaction mixture was
(400 MHz, CDCl3): δ 7.69 (dd, J = 25.9, 8.4 Hz, 1H, Ar-H), 7.62- extracted with ethyl acetate (10 mLX3) and organic layer was
7.51 (m, 3H, Ar-H), 7.51-7.39 (m, 3H, Ar-H), 6.95-6.75 (m, 2H, dried over sodium sulphate and crude product was purified by
Ar-H), 3.87 (s, 3H, -OCH3), 3.20 (s, 4H, -CH2), 3.02-2.75 (m, 4H, - column chromatography with DCM/hexane (3:17) as eluent.
CH2), 1.73 (d, J = 15.3 Hz, 6H, -CH2); 13C-NMR (100 MHz, CDCl3): yield: 75%; 0.7 Rf (10% ethylacetate in hexane), white solid; 1H-
δ 192.1, 159.9, 154.1, 151.2, 144.5, 143.6, 141.9, 133.0, 131.2, NMR (400 MHz, CDCl3): δ 7.69 (dd, J = 8.0, 1.0 Hz, 1H, Ar-H),
129.9, 128.5, 127.4, 123.3, 121.1, 119.3, 113.3, 112.4, 111.5, 7.38-7.40 (m, 2H, Ar-H), 7.26-7.31 (m, 1H, Ar-H), 7.21 (d, J = 1.5
106.9, 55.3, 51.2, 26.9, 26.8, 24.4, 23.3; IR: 2927, 2850, 1699 Hz, 1H, Ar-H), 7.13 (d, J = 1.6 Hz, 1H, Ar-H), 7.09 (dd, J = 5.1, 3.7
(CO), 1605, 1539 cm-1; HRMS (m/z): [M+H]+ calcd for Hz, 1H, Ar-H), 3.25 (t, J = 4.4 Hz, 4H, -CH2), 1.80 (m, 4H, -CH2),
C27H26NO2: 396.1958; found: 396.1963.
1.61 (t, J = 5.8 Hz, 2H, -CH2); 13C-NMR (100 MHz, CDCl3): δ
10 | J. Name., 2012, 00, 1-3
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ARTICLE
Wang, J. Guan and A. Wu, Tetrahedron, 2014, 70, 1412; (e)
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Conflicts of interest
There are no conflicts to declare.
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