Chemoselective synthesis of m-teraryls through ring transformation of 2 H-pyran-2-ones by 2-(1-arylethylidene)-malononitriles

Article abstract of DOI:10.1039/c8ob02370k

We have developed a simple, efficient and chemoselective approach for the synthesis of m-teraryls by the reaction of 6-aryl-2-oxo-4-(sec.amino)-2H-pyran-3-carbonitriles and 2-(1-arylethylidene)malononitriles under basic conditions. We used 6-aryl-2-oxo-4-

Full text of DOI:10.1039/c8ob02370k

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Chemoselective synthesis of m-teraryls through
ring transformation of 2H-pyran-2-ones by
2-(1-arylethylidene)-malononitriles†
Cite this: Org. Biomol. Chem., 2018,
16, 8994
Rahul Panwar, Shally, Ranjay Shaw, Amr Elagamy and Ramendra Pratap
*
We have developed a simple, efficient and chemoselective approach for the synthesis of m-teraryls by the
reaction of 6-aryl-2-oxo-4-(sec.amino)-2H-pyran-3-carbonitriles and 2-(1-arylethylidene)malononitriles
under basic conditions. We used 6-aryl-2-oxo-4-methylsulfanyl-2H-pyran-3-carbonitriles as precursors
and successfully afforded 5’-methylsulfanyl-[1,1’;3’,1’’]teraryl-4’-carbonitriles. We tried to understand the
difference in the reactivity of structurally symmetrical molecules, such as allyl cyanide, 2-cyanomethyl-
benzonitrile and 2-(1-arylethylidene)malononitrile. The structure of 4’’-methyl-5’-(piperidin-1-yl)-
[1,1’:3’,1’’-terphenyl]-4’-carbonitrile was confirmed by single crystal X-ray diffraction analysis.
Received 23rd September 2018,
Accepted 31st October 2018
DOI: 10.1039/c8ob02370k
rsc.li/obc
2,3,3a,4,7,7a-hexahydroindole.14d Herein, we envisage that
2-(1-arylethylidene)malononitriles can act as nucleophile
Introduction
α,α-Dicyanoolefins are readily accessible through the sources to afford 5′-sec.amino/methylsulphanyl-[1,1′;3′,1″]
Knoevenagel reaction of the corresponding aromatic/hetero- teraryl-4′-carbonitriles.
aromatic/aliphatic aldehydes or ketones with malononitrile.1
m-Teraryls are widely used in the fields of medicinal and
These compounds are widely used in synthetic organic chem- industrial chemistry15–18 such as liquid crystals, conducting
istry due to their use as Michael acceptors2 as well as sources polymers, heat storage and transfer agents, textile dye carriers,
of nucleophiles.3 Various reactions of 2-(1-arylethylidene)malo- and laser dyes.19–21 Very few methods are reported for the syn-
nonitriles were reported for the construction of multifunc- thesis of polyarenes. The most widely used approach for the
tional moieties.4–10 These compounds were subjected to synthesis of m-teraryls is metal-catalyzed one-pot or stepwise
various chemical reactions, such as reaction with cross-coupling reaction of aromatic halides with organo-
α,α-dicyanoolefins to afford benzene,4 allylic alkylation with metallic species such as cross coupling reactions of dihaloben-
Morita–Baylis–Hillman carbonates,5 direct asymmetric vinylo- zene with aryl nucleophiles (arylboronic acids, arylmagnesium
gous Mannich reaction,6 allylic amination,7 [3 + 2] annula- bromides, arylstannyl halides etc.).22 Teraryls were also
tion,8 γ-trifluoromethylation9 and asymmetric Michael achieved by transition metal-catalyzed [2 + 2 + 2] and [4 + 2]
addition reactions.10 Recently, polyfunctional cyclohexadienes
were synthesized by vinylogous addition of α,α-dicyanoolefins
to Michael intermediates obtained by the reaction of dialkyl
acetylenedicarboxylates and malononitrile.11 Recently, our
research group has reported the reactivity of allyl cyanide for
the synthesis of multifunctional benzene12 (Fig. 1).
2H-Pyran-2-ones are excellent precursors and extensively
explored as Michael acceptors in synthetic organic chemistry13
and reacted with a wide variety of nucleophile sources to
afford various arenes and heteroarenes.13,14 2H-Pyran-2-ones
are also used as Diels–Alder precursors to construct
Department of Chemistry, University of Delhi, North campus, Delhi, India-110007.
E-mail: ramendrapratap@gmail.com; Tel: +911127666646
†Electronic supplementary information (ESI) available: All the proton and 13C
NMR spectra. CCDC 1869248. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c8ob02370k
Fig. 1 Comparison of previous approaches versus this approach.
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Table 1 Effect of base and solvent on the synthesis of 3a a
cycloadditions of diaryl-substituted open chain precursors and
these reactions have been extensively reviewed.23 It is impor-
tant to note that limited availability of organometallic coupling
partners and functional group compatibility (e.g., carbonyls,
enones) reduce the scope of the reaction.24 The cycloaddition
approach acts as a valuable protocol to assemble polysubsti-
tuted benzenes and teraryls, but these methods suffer from
chemo- and regioselectivity. Due to the high importance of
m-teraryls, we planned an efficient approach for their
synthesis.
Temperature
(°C)
Time
(h)
Yieldb
(%) 3a
Entry
Base
Solvent
c
1
2
3
4
5
6
7
8
NaNH2
NaNH2
NaNH2
NaNH2
NaNH2
KOH
KOH
KOH
NaH
NaH
NaH
KOtBu
KOH
KOH
NaH
NaNH2
t-BuOK
Cs2CO3
LiOH
DMSO
DMSO
DMSO
DMSO
DMF
DMSO
DMSO
DMF
DMSO
DMSO
DMF
DMSO
THF
r.t.
60
90
120
90
r.t.
90
90
r.t.
90
90
90
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
12
12
8
—
d
—
d
Results and discussion
—
d
8
—
d
12
12
12
12
12
12
12
12
6
6
6
12
12
12
12
—
To begin the study, we have synthesized the various required
d
—
precursors,
6-aryl-4-(methylthio)-2-oxo-2H-pyran-3-carbo-
d
—
d
nitriles, 6-aryl-4-sec.amino-2-oxo-2H-pyran-3-carbonitriles and
2-(1-(aryl)ethylidene)malononitriles, as per literature methods.
The functionalized 2H-pyran-2-ones were synthesized in two
steps.25 At first, ethyl 2-cyano-3,3-bis(methylthio)acrylate was
treated with aryl methyl ketones in DMSO under basic con-
ditions to afford 6-aryl-4-(methylthio)-2-oxo-2H-pyran-3-carbo-
nitriles. In the next step amination of 6-aryl-4-(methylthio)-
2-oxo-2H-pyran-3-carbonitrile with the secondary amine was
carried out in reflux ethanol to afford 6-aryl-2-oxo-4-(sec.
amino)-2H-pyran-3-carbonitriles. The other precursors 2-(1-
(aryl)ethylidene)malononitriles were afforded by the reaction
of aryl methyl ketone and malononitrile under mild
conditions.26
—
d
9
—
d
10
11
12
13
14
15
16
17
18
19
—
d
—
d
—
80
60
35
45
45
25
25
1,4-Dioxane
THF
THF
THF
THF
THF
a All reactions were carried out by stirring 2-oxo-6-phenyl-4-(piperidin-
1-yl)-2H-pyran-3-carbonitrile 1 (0.5 mmol) and 2-(1-(p-tolyl)ethylidene)
malononitrile 2 (0.5 mmol) in various solvents (5.0 mL) using different
bases (1.0 mmol) at different temperatures. b Isolated yields. c Both
starting materials were recovered (1, 2). d Complex mixture formation.
To optimize the reaction condition, 2-oxo-6-phenyl-4-
(piperidin-1-yl)-2H-pyran-3-carbonitrile and 2-(1-(p-tolyl)ethyli-
dene)malononitrile were chosen as model substrate. At first
an equimolar mixture was stirred with NaNH2 in DMSO at tionalized m-teraryls. We synthesized a series of 2,4-diaryl-6-
room temperature and the starting materials were recovered (sec.amino)benzonitriles (functionalized m-teraryls) in good
(entry 1, Table 1). Then, we performed the reaction using sod- yields under the optimized reaction conditions. We have suc-
amide in DMSO at 60, 90 and 120 °C and in DMF at 90 °C and cessfully installed various aryl and heteroaryl groups into the
a complex mixture was formed (entries 2–5, Table 1). We also benzene nuclei and observed excellent compatibility of the
used other bases like potassium hydroxide and sodium reaction conditions with various functional groups.
hydride in DMSO and DMF at room temperature and high Interestingly, the presence of both electron-donating and with-
temperature, but a complex mixture was obtained (entries drawing groups in the benzene ring of the precursors does not
6–11, Table 1). The use of potassium tertiary butoxide in have a significant influence on the yield of 2,4-diaryl-6-(sec.
DMSO at 90 °C provided a complex mixture (entry 12, Table 1). amino)benzonitriles (Scheme 1).
We found that polar solvents are not suitable for the reaction
The structure of compound 4″-methyl-5′-(piperidin-1-yl)-
and we performed the reaction in THF and 1,4-dioxane in the [1,1′:3′,1″-terphenyl]-4′-carbonitrile 3i was confirmed by single
presence of potassium hydroxide under reflux condition and crystal X-ray analysis. The central benzene ring contains two
80 and 60% of m-teraryls were obtained respectively (entries 13 aryl groups, one piperidine group and one nitrile group. The
and 14, Table 1). From this result, we found that THF acted as piperidine group exists in chair form. One unit cell contains
the best solvent and we tried various other bases like sodium four molecules. There is no H-bonding present between and
hydride, sodamide, potassium tertiary butoxide, cesium car- within the molecule. Both aryl rings are in different planes
bonate and lithium hydroxide in THF under reflux condition and have different dihedral angles (Fig. 2).
but only lower yield were obtained (entries 15–19, Table 1).
To further expand the scope of the reaction, we used 6-aryl-
precursor
The optimization of the reaction conditions shows that stir- 4-(methylthio)-2-oxo-2H-pyran-3-carbonitrile as
a
ring of an equimolar mixture of 2-pyranone and 2-(1-(aryl)ethy- and treated it with 2-(1-arylethylidene)malononitriles under
lidene)malononitriles in THF and potassium hydroxide at the same reaction condition and successfully afforded 2,4-
reflux temperature provided the best yield. Then the generality diaryl-6-(methylthio)benzonitriles in low to average yields.
of the protocol was tested for the synthesis of a series of func- Previously, we used 6-aryl-4-(methylthio)-2-oxo-2H-pyran-3-car-
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Scheme 1 Synthesis of various 2,4-diaryl-6-(sec.amino)benzonitriles [reaction conditions: 2H-pyran-2-ones 1 (0.5 mmol), 2-(1-(aryl)ethylidene)
malononitriles 2 (0.5 mmol), KOH (1.0 mmol) and THF (5.0 mL) were stirred for 6 h under reflux condition; isolated yields].
bonitriles with aryl methyl ketone under basic conditions and
pyran was obtained. It was reported that precursor 4 always
leads to side reactions due to the better leaving group pro-
perties of the thiomethyl group and probably at higher temp-
erature some of the precursors undergo decomposition to
afford a low yield of the product (Scheme 2).
Recently, we have reported the reaction of allyl cyanide and
2-cyanomethylbenzonitrile with 2H-pyran-2-ones under basic
conditions and afforded the functionalized benzene and
benzo[h]quinolines respectively (Scheme 3). The structural
relationship of allyl cyanide and 2-cyanomethylbenzonitrile
with 2-(1-arylethylidene)malononitriles clearly indicates that
they might provide the same reactivity but surprisingly they
don’t behave in the same way (Fig. 3).
If we carefully observe the structure, all of them can act as
sources of nucleophiles under basic conditions and can be
Fig. 2 ORTEP diagram of 4-bromo-4’’-methyl-5’-(piperidin-1-yl)-
[1,1’:3’,1’’-terphenyl]-4’-carbonitrile 3i.
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Scheme 2 Synthesis of 2,4-diaryl-6-(methylthio)benzonitriles and pyran [reaction conditions: 2H-pyran-2-ones 1 (0.5 mmol), 2-(1-(aryl)ethylidene)
malononitriles 2 (0.5 mmol), KOH (1.0 mmol) and THF (5.0 mL) were stirred for 6 h under reflux condition; isolated yields].
Scheme 3 Comparison of the reactivity of various nucleophile sources
[2-cyanomethylbenzonitrile (I) and allyl cyanide (II)] with 2-pyranone.
Fig. 3 Structural comparison of 2-cyanomethylbenzonirile (I), allyl
cyanide (II) and 2-(1-arylethylidene)malononitrile (2).
Scheme 4 Proposed mechanism for the synthesis of 2,4-diaryl-6-(sec.
used for 4 + 2 annulation reactions.27 Alternatively, allyl cyanide
amino)/methylsulfanyl-benzonitriles.
reacts with 2H-pyran-2-ones and the insertion of both C2–C3 and
C3–C4 was observed, whereas in the present case 2, only selective
insertion of C3–C4 was observed without any side reaction.12a,b erates and resonates at the C3 position of pyran and cyclizes
Structural detection of 2H-pyran-2-ones shows that positions C2, through Michael addition at alkylidene malononitrile to afford
C4 and C6 are the electrophilic centers, among which the latter intermediate C. Intermediate C undergoes loss of malono-
is more interactive towards the nucleophile due to extended con- nitrile and provides m-teraryls 3.
jugation with the nitrile and carbonyl groups.
In order to probe the mechanism, we tried to isolate the
On the basis of the results obtained, we have proposed the ring open intermediate B but failed. Therefore, we proposed
mechanism and depicted it in Scheme 4. In the presence of a that as soon as ring opening occurs further steps occur consecu-
base, the carbanion generated from alkylidene malononitrile tively. If we compare 2-(1-arylethylidene)malononitrile with
attacks at the C6 position of 2H-pyran-2-ones followed by ring 2-cyanomethylbenzonitrile, the latter had no scope of Michael
opening to afford intermediate A. Then intermediate A under- addition but the former could involve the nitrile group as pro-
goes decarboxylation followed by protonation to afford inter- posed earlier. Interestingly, no quinoline formation was
mediate B. In the presence of excess base, the carbanion gen- observed during the reaction. On the other hand, 2-(1-arylethyl-
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idene)malononitrile reacted in the same way as allyl cyanide but J = 8 Hz, 2H, ArH), 7.30–7.41 (m, 5H, ArH), 7.5 (d, J = 8 Hz, 2H,
provided m-teraryls exclusively due to steric reasons.
ArH); 13C NMR (100 MHz, CDCl3): δ 21.2, 24.0, 26.1, 53.6,
104.2, 116.0, 118.2, 121.4, 127.2, 128.4, 128.7, 129.0, 129.2,
136.0, 138.4, 140.0, 146.0, 147.8, 158.6; HRMS (ESI): calculated
for C25H25N2, 353.2012 (MH+); found: m/z, 353.2014.
Experimental
General remarks
4″-Methyl-5′-morpholino-[1,1′:3′,1″-terphenyl]-4′-carbonitrile (3b)
Yield: 79% (140 mg); white solid; mp: 120–122 °C; IR (KBr):
To carry out the reaction, commercial reagents were used
directly without any further purification. The solvent THF was
dried over sodium under a nitrogen atmosphere before being
used for the reaction. The 1H and 13C NMR spectra were
recorded on 400 MHz NMR and 100 MHz NMR spectrometers
in CDCl3. The chemical shift values are reported as parts per
million (δ-value) and the proton NMR peak of CDCl3 (δ =
1
2215 cm−1; H NMR (400 MHz, CDCI3): δ 2.41 (s, 3H, –CH3),
3.28–3.32 (m, 4H, –CH2), 3.91–3.94 (m, 4H, –CH2), 7.16 (s, 1H,
ArH), 7.29–7.31 (m, 3H, ArH), 7.41–7.48 (m, 5H, ArH), 7.5 (d,
J = 8 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ 21.2, 52.2,
67.0, 104.3, 115.7, 118.0, 122.4, 127.2, 128.5, 128.6, 129.0,
129.2, 135.6, 138.6, 139.6, 146.2, 148.1, 157.1; HRMS (ESI): cal-
culated for C24H23N2O, 355.1805 (MH+); found: m/z, 355.1803.
1
7.24 ppm for H) or the middle peak of CDCl3 in the 13C NMR
spectra (δ 77.00 ppm) was used as an internal reference. The
splitting patterns are represented as s, singlet; d, doublet; dd,
double doublet; t, triplet; bs, broad singlet; m, multiplets.
Coupling constants (J) are given in hertz (Hz).
4,4″-Dimethyl-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3c)
Yield: 79% (145 mg); white solid; mp: 110–112 °C; IR (KBr):
2214 cm−1 1H NMR (400 MHz, CDCI3): δ 1.58–1.61 (m, 2H,
;
General procedure for the synthesis of 2-(1-arylethylidene)
malononitrile
–CH2), 1.70–1.80 (m, 4H, –CH2), 2.39 (s, 6H, –2CH3), 3.20–3.24
(m, 4H, –CH2), 7.12 (s, 1H, ArH), 7.18 (s, 1H, ArH), 7.25 (t, J =
12 Hz, 4H, ArH), 7.46 (t, J = 16 Hz, 4H, ArH); 13C NMR (100 MHz,
CDCl3): δ 21.2, 21.3, 24.2, 26.3, 53.7, 104.1, 115.8, 118.4, 121.4,
127.2, 129.0, 129.3, 129.7, 136.2, 137.1, 138.5, 138.5, 146.0, 148.0,
158.7; HRMS (ESI): calculated for C26H27N2, 367.2169 (MH+);
found: m/z, 367.2167.
To a vacuum dried 100 ml round-bottom flask malononitrile
(3.17 g, 48.0 mmol), ammonium acetate (0.740 g, 9.60 mmol)
and functionalized aryl methyl ketone (48 mmol) were added.
To this mixture, CH3COOH (3.0 ml, 52.8 mmol) and toluene
(30 ml) were added. The round-bottom flask was fitted with a
Dean–Stark apparatus and the reaction mixture was refluxed for
1–2 h. The reaction mixture was cooled to room temperature
and diluted with toluene (50 mL). The organic layer was washed
with saturated sodium bicarbonate solution (50.0 mL × 3) and
water (50.0 mL × 2). The organic layer was dried over MgSO4
and concentrated under vacuum and the resulting solid was
recrystallized from ethanol to isolate the desired compound.
4,4″-Dimethyl-5′-morpholino-[1,1′:3′,1″-terphenyl]-4′-carbonitrile
(3d)
Yield: 80% (147 mg); white solid; mp: 123–125 °C; IR (KBr):
1
2216 cm−1; H NMR (400 MHz, CDCI3): δ 2.39 (s, 3H, –CH3),
(2.40, s, 3H, –CH3), 3.27–3.29 (m, 4H), 3.91–3.93 (m, 4H), 7.14
(s, 1H, ArH), 7.2 (t, J = 16 Hz, 5H, ArH), 7.44–7.52 (m, 4H,
ArH); 13C NMR (100 MHz, CDCl3): δ 21.1, 21.2, 52.2, 67.0,
104.0, 115.5, 118.0, 127.0, 128.7, 129.2, 129.7, 130.8, 135.8,
136.7, 138.6, 138.7, 146.2, 148.0, 157.1; HRMS (ESI): calculated
for C25H25N2O, 369.1961(MH+); found: m/z, 369.1963.
General procedure for the synthesis of 2,4-diaryl-6-(sec.amino)
benzonitriles (3a–t) and 2,4-diaryl-6-(methylthio)benzonitriles
(5a–d)
A
mixture of 6-aryl-2-oxo-4-sec.amino-1-yl-2H-pyran-3-carbo-
4-Methoxy-4″-methyl-5′-morpholino-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3e)
nitriles/6-aryl-4-(methylthio)-2-oxo-2H-pyran-3-carbonitriles
(0.5 mmol), 2-(1-arylethylid-ne)malononitrile (0.5 mmol), and
KOH (1.0 mmol) in THF (5.0 ml) was stirred under reflux con-
ditions for 6 h. After the completion of the reaction, excess THF
was removed under reduced pressure, and the reaction mixture
was poured onto crushed ice with vigorous stirring followed by
neutralization with 10% hydrochloric acid. The precipitate
obtained was filtered, washed with H2O, and dried. The solid
mixture was purified by silica gel column chromatography using
hexane–ethylacetate (90 : 10) as an eluent to afford m-teraryls.
Yield: 73% (140 mg); white solid; mp: 90–92 °C; IR (KBr):
1
2214 cm−1; H NMR (400 MHz, CDCI3): δ 2.40 (s, 3H, –CH3),
3.26–3.28 (m, 4H, –CH2), 3.84 (s, 3H, –OMe), 3.91–3.93 (m, 4H,
–CH2), 6.97 (d, J = 12 Hz, 2H, ArH), 7.11 (s, 1H, ArH), 7.27 (d,
J = 8 Hz, 3H, ArH), 7.45 (d, J = 8 Hz, 2H, ArH), 7.53 (d, J = 8 Hz,
2H, ArH); 13C NMR (100 MHz, CDCl3): δ 21.2, 52.2, 55.3, 67.0,
103.6, 114.3, 115.1, 118.0, 122.0, 128.3, 128.6, 129.2, 132.0,
135.8, 138.5, 145.7, 148.0, 157.1, 160.1; HRMS (ESI): calculated
for C25H25N2O2, 385.1911 (MH+); found: m/z, 385.1891.
4″-Methyl-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3a)
4-Fluoro-4″-methyl-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3f)
Yield: 80% (141 mg); white solid; mp: 145–147 °C; IR (KBr):
2214 cm−1; H NMR (400 MHz, CDCI3): δ 1.18 (s, 2H, –CH2), Yield: 79% (146 mg); white solid; mp: 128–130 °C; IR (KBr):
1
1.70–1.80 (m, 4H, –CH2), 2.33 (s, 3H, –CH3), 3.15–3.18 (m, 4H, 2214 cm−1
;
1H NMR (400 MHz, CDCI3): δ 1.61–1.65 (m, 2H,
–CH2), 7.06–7.08 (m, 1H, ArH), 7.13–7.14 (m, 1H, ArH), 7.2 (d, –CH2), 1.80–1.85 (m, 4H, –CH2), 2.41 (s, 3H, –CH3), 3.23–3.26
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(m, 4H, –CH2), 7.09 (s, 1H, ArH), 7.11–7.15 (m, 3H, ArH), 7.2 3,4-Dimethoxy-4″-methyl-5′-(piperidin-1-yl)-[1,1′:3′,1″-
(d, J = 12 Hz, 2H, ArH), 7.4 (d, J = 8 Hz, 2H, ArH), 7.54–7.57 (m, terphenyl]-4′-carbonitrile (3k)
2H, ArH); 13C NMR (100 MHz, CDCl3): δ 21.2, 24.0, 26.1, 53.6,
104.2, 115.8 (d, JC–F = 20 Hz), 118.1, 121.2, 128.7, 128.8 (d, JC–F
= 10 Hz), 129.2, 136.0, 136.0, 138.5, 144.8, 148.0, 158.6, 163 (d,
JC–F = 250 Hz); HRMS (ESI): calculated for C25H24FN2, 371.1918
(MH+); found: m/z, 371.1915.
Yield: 68% (140 mg); white solid; mp: 155–157 °C; IR (KBr):
2213 cm−1 1H NMR (400 MHz, CDCI3): δ 1.60–1.63 (m, 2H,
;
–CH2), 1.79–1.85 (m, 4H, –CH2), 2.41 (s, 3H, –CH3), 3.23–3.26
(m, 4H, –CH2), 3.93 (s, 3H, –OMe), 3.94 (s, 3H, –OMe),
6.94–6.96 (m, 1H, ArH), 7.07 (s, 1H, ArH), 7.11 (s, 1H, ArH),
7.15–7.16 (m, 2H, ArH), 7.28 (d, J = 4 Hz, 2H, ArH), 7.46–7.48
(m, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ 21.2, 24.0, 26.1,
53.6, 55.9, 56.0, 103.7, 110.2, 111.3, 115.5, 118.2, 119.8, 121.1,
128.7, 129.2, 132.8, 136.1, 138.4, 145.7, 147.8, 149.2, 149.4,
158.6; HRMS (ESI): calculated for C27H29N2O2, 413.2224
(MH+); found: m/z, 413.2233.
4-Fluoro-4″-methyl-5′-morpholino-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3g)
Yield: 77% (143 mg); white solid; mp: 140–142 °C; IR (KBr):
1
2215 cm−1; H NMR (400 MHz, CDCI3): δ 2.42 (s, 3H, –CH3),
3.29–3.31 (m, 4H, –CH2), 3.93–3.95 (m, 4H, –CH2), 7.11 (s, 1H,
ArH), 7.1 (t, J = 16 Hz, 2H, ArH), 7.2 (d, J = 8 Hz, 1H, ArH), 7.3
(d, J = 8 Hz, 2H, ArH), 7.4 (d, J = 8Hz, 2H, ArH), 7.55–7.58 (m,
2H, ArH); 13C NMR (100 MHz, CDCl3): δ 21.6, 52.2, 67.0, 104.4,
2,4-Dichloro-4″-methyl-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-
4′-carbonitrile (3l)
115.5, 116.0 (d, JC–F = 30 Hz), 117.8, 122.3, 128.7, 129.0 (d, JC–F
60 Hz), 129.3, 135.6, 138.7, 145.2, 148.3, 157.2, 163.0 (d, JC–F
=
=
Yield: 68% (137 mg); white solid; mp: 95–97 °C; IR (KBr):
2216 cm−1 1H NMR (400 MHz, CDCI3): δ 1.62–1.64 (m, 2H,
;
250 Hz); HRMS (ESI): calculated for C24H22FN2O, 373.1711
–CH2), 1.78–1.83 (m, 4H, –CH2), 2.41 (s, 3H, –CH3), 3.22–3.24
(m, 4H), 6.99 (s, 1H, ArH), 7.02 (s, 1H, ArH), 7.28–7.33 (m, 4H,
ArH), 7.46 (d, J = 8 Hz, 2H, ArH), 7.51–7.52 (m, 1H, ArH); 13C
NMR (100 MHz, CDCl3): δ 21.3, 24.1, 26.2, 53.6, 105.0, 118.1,
118.4, 123.4, 127.4, 129.0, 129.4, 130.0, 131.8, 133.1, 134.6,
135.7, 138.0, 138.7, 143.0, 147.5, 158.1; HRMS (ESI): calculated
for C25H23Cl2N2, 421.1233 (MH+); found: m/z, 421.1233.
(MH+); found: m/z, 373.1717.
4-Chloro-4″-methyl-5′-morpholino-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3h)
Yield: 78% (152 mg); white solid; mp: 125–127 °C; IR (KBr):
2215 cm−1 1H NMR (400 MHz, CDCI3): δ 2.42 (s, 3H, –CH3),
;
3.28–3.30 (m, 4H, –CH2), 3.92–3.95 (m, 4H, –CH2), 7.21 (s, 1H,
ArH), 7.25 (s, 1H, ArH), 7.2 (d, J = 8 Hz, 2H, ArH), 7.4 (t, J =
16 Hz, 4H, ArH), 7.51–7.53 (m, 2H, ArH); 13C NMR (100 MHz,
CDCl3): δ 21.3, 52.2, 67.0, 104.6, 115.5, 117.8, 122.2, 128.5,
128.7, 129.2, 129.3, 134.8, 135.5, 138.0, 138.8, 145.0, 148.3,
157.2; HRMS (ESI): calculated for C24H22ClN2O, 389.1415
(MH+); found: m/z, 389.1414.
2,4-Dichloro-4″-methyl-5′-morpholino-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3m)
Yield: 58% (125 mg); white solid; mp: 100–102 °C; IR (KBr):
1
2214 cm−1; H NMR (400 MHz, CDCI3): δ 2.31 (s, 3H, –CH3),
3.18–3.20 (m, 4H, –CH2), 3.82–3.85 (m, 4H, –CH2), 6.93 (s, 1H,
ArH), 7.02 (s, 1H, ArH), 7.18–7.25 (m, 4H, ArH), 7.37 (d, J = 8
Hz, 2H, ArH), 7.42–7.43 (m, 1H, ArH); 13C NMR (100 MHz,
CDCl3): δ 21.2, 52.1, 67.0, 105.0, 117.6, 118.1, 124.4, 127.3,
128.7, 129.3, 130.0, 131.6, 133.0, 134.7, 135.2, 137.4, 138.7,
143.1, 147.6, 156.4; HRMS (ESI): calculated for C24H21Cl2N2O,
423.1025 (MH+); found: m/z, 423.1026.
4-Bromo-4″-methyl-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3i)
Yield: 78% (168 mg); white solid; mp: 126–128 °C; IR (KBr):
2214 cm−1 1H NMR (400 MHz, CDCI3): δ 1.57–1.62 (m, 2H,
;
–CH2), 1.63–1.80 (m, 4H, –CH2), 2.40 (s, 3H, –CH3), 3.21–3.24
(m, 4H, –CH2), 7.08 (s, 1H, ArH), 7.14 (s, 1H, ArH), 7.26 (d, J =
8 Hz, 2H, ArH), 7.43–7.45 (m, 4H, ArH), 7.56 (d, J = 8 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3): δ 20.5, 23.3, 25.4, 53.0,
103.8, 115.0, 117.3, 120.4, 122.0, 128.0, 128.5, 131.3, 135.1,
137.8, 138.1, 144.0, 147.4, 158.0; HRMS (ESI): calculated for
C25H24BrN2, 433.1102 (MH+ + 2); found: m/z, 433.1097.
4′-Methyl-3-(piperidin-1-yl)-5-(thiophen-2-yl)-[1,1′-biphenyl]-2-
carbonitrile (3n)
Yield: 75% (134 mg); white solid; mp: 108–110 °C; IR (KBr):
2214 cm−1 1H NMR (400 MHz, CDCI3): δ 1.61–1.66 (m, 2H,
;
–CH2), 1.79–1.85 (m, 4H, –CH2), 2.42 (s, 3H, –CH3), 3.24 (t, J =
8 Hz, 4H, –CH2), 7.1 (t, J = 8 Hz, 1H, ArH), 7.17 (s, 1H, ArH),
7.24 (s, 1H, ArH), 7.29 (d, J = 8 Hz, 2H, ArH), 7.36 (d, J = 4 Hz,
1H, ArH), 7.39 (d, J = 4 Hz, 1H, ArH), 7.47 (d, J = 8 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3): δ 21.2, 24.0, 26.1, 53.6,
104.5, 115.6, 118.0, 121.1, 122.7, 128.7, 128.8, 129.2, 132.0,
135.8, 138.5, 138.8, 144.6, 148.0, 158.7; HRMS (ESI): calculated
for C23H23N2S, 359.1576 (MH+); found: m/z, 359.1572.
4-Bromo-4″-methyl-5′-morpholino-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3j)
Yield: 74% (160 mg); white solid; mp: 98–100 °C; IR (KBr):
1
2215 cm−1; H NMR (400 MHz, CDCI3): δ 2.42 (s, 3H, –CH3),
3.29–3.31 (m, 4H, –CH2), 3.93–3.95 (m, 4H, –CH2), 7.11 (s, 1H,
ArH), 7.25 (s, 1H, ArH), 7.3 (d, J = 8 Hz, 2H, ArH), 7.46 (d, J =
8 Hz, 4H, ArH), 7.6 (d, J = 8 Hz, 2H, ArH); 13C NMR (100 MHz,
CDCl3): δ 21.2, 52.2, 67.0, 104.7, 115.4, 117.8, 122.2, 123.0,
128.7, 128.8, 129.3, 132.1, 135.5, 138.4, 138.8, 145.0, 148.4,
4′-Methyl-3-morpholino-5-(thiophen-2-yl)-[1,1′-biphenyl]-2-
carbonitrile (3o)
157.1; HRMS (ESI): calculated for C24H22BrN2O, 433.0910 Yield: 76% (137 mg); white solid; mp: 100–102 °C; IR (KBr):
1
(MH+); found: m/z, 433.0906.
2213 cm−1; H NMR (400 MHz, CDCI3): δ 2.34 (s, 3H, –CH3),
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3.19–3.22 (m, 4H, –CH2), 3.84–3.86 (m, 4H, –CH2), 7.02–7.04 4′-Chloro-3-(piperidin-1-yl)-5-(thiophen-2-yl)-[1,1′-biphenyl]-4-
(m, 1H, ArH), 7.09 (s, 1H, ArH), 7.20–7.22 (m, 3H, ArH), 7.30 carbonitrile (3t)
(d, J = 4 Hz, 1H, ArH), 7.33 (d, J = 8 Hz, 1H, ArH), 7.38 (d, J =
Yield: 65% (123 mg); white solid; mp: 98–100 °C; IR (KBr):
8 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): δ 21.2, 52.1, 67.0,
104.1, 114.0, 117.8, 120.8, 125.0, 126.8, 128.3, 128.6, 129.3,
135.4, 138.7, 139.0, 142.4, 148.3, 157.1; HRMS (ESI): calculated
for C22H21N2OS, 361.1369 (MH+); found: m/z, 361.1369.
1
2215 cm−1; H NMR (400 MHz, CDCI3): δ 0.90 (bs, 2H, –CH2),
1.09 (bs, 4H, –CH2), 2.50 (bs, 4H, –CH2), 6.33–6.35 (m, 1H,
ArH), 6.40–6.42 (m, 1H, ArH), 6.52–6.54 (m, 1H, ArH),
6.69–6.71 (m, 3H, ArH), 6.70–6.79 (m, 2H, ArH), 6.86–6.87 (m,
1H, ArH); 13C NMR (100 MHz, CDCl3): δ 23.3, 25.4, 53.0, 103.0,
115.6, 117.4, 120.5, 126.4, 127.2, 127.4, 127.8, 128.5, 134.1,
137.4, 139.2, 144.2, 158.7; HRMS (ESI): calculated for
C22H20ClN2S, 379.1030 (MH+); found: m/z, 379.1032.
4-Chloro-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-4′-carbonitrile
(3p)
Yield: 70% (130 mg); white solid; mp: 115–117 °C; IR (KBr):
2215 cm−1 1H NMR (400 MHz, CDCI3): δ 0.95–0.96 (m, 2H,
;
4,4″-Dimethyl-5′-(methylthio)-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (5a)
–CH2), 1.14–1.15 (m, 4H, –CH2), 2.58–2.59 (m, 4H, –CH2),
6.46–6.50 (m, 2H, ArH), 6.74 (m, 9H, ArH); 13C NMR (100 MHz,
CDCl3): δ 23.4, 26.0, 53.0, 104.0, 115.3, 117.3, 120.6, 128.0, Yield: 45% (74 mg); white solid; mp: 112–114 °C; IR (KBr):
1
128.3, 128.5, 134.0, 137.7, 138.6, 144.0, 147.4, 158.1; HRMS 2214 cm−1; H NMR (400 MHz, CDCI3): δ 2.42 (s, 6H, –2CH3),
(ESI): calculated for C24H22ClN2, 373.1466 (MH+); found: m/z, 2.58 (s, 3H, –SMe), 7.25–7.31 (m, 4H, ArH), 7.41–7.41 (m, 1H,
373.1462.
ArH), 7.47–7.52 (m, 3H, ArH), 7.8 (d, J = 8 Hz, 2H, ArH); 13C
NMR (100 MHz, CDCl3): δ 16.3, 21.3, 22.0, 104.8, 115.8, 117.1,
121.2, 128.3, 129.4, 129.7, 129.8, 134.3, 135.3, 139.1, 144.5,
145.5, 147.6, 148.1; HRMS (ESI): calculated for C22H20NS,
330.1311 (MH+); found: m/z, 330.1313.
4-Chloro-4″-methoxy-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3q)
Yield: 68% (137 mg); white solid; mp: 105–107 °C; IR (KBr):
2215 cm−1 1H NMR (400 MHz, CDCI3): δ 0.96–0.97 (m, 2H,
;
4′-Methyl-3-(methylthio)-5-(thiophen-2-yl)-[1,1′-biphenyl]-2-
–CH2), 1.13–1.14 (m, 4H, –CH2), 2.56–2.57 (m, 4H, –CH2), 3.18
(s, 3H, –OMe), 6.30–6.33 (m, 2H, ArH), 6.41 (s, 1H, ArH), 6.47
(s, 1H, ArH), 6.73–6.76 (m 2H, ArH), 6.83–6.86 (m, 4H, ArH);
13C NMR (100 MHz, CDCl3): δ 23.4, 25.5, 53.0, 54.7, 103.8,
113.0, 115.0, 117.4, 120.6, 127.3, 128.5, 129.5, 130.3, 134.0,
137.8, 144.0, 147.1, 158.1, 159.4; HRMS (ESI): calculated for
C25H24ClN2O, 403.1572 (MH+); found: m/z, 403.1576.
carbonitrile (5b)
Yield: 43% (69 mg); white solid; mp: 95–97 °C; IR (KBr):
1
2214 cm−1; H NMR (400 MHz, CDCI3): δ 2.42 (s, 3H, –CH3),
2.64 (s, 3H, –SMe), 7.12–7.14 (m, 1H, ArH), 7.3 (d, J = 8 Hz, 2H,
ArH), 7.39–7.45 (m, 3H, ArH), 7.45–7.48 (m, 3H, ArH); 13C
NMR (100 MHz, CDCl3): δ 16.5, 21.2, 104.9, 116.1, 117.0, 121.5,
128.3, 128.5, 129.4, 135.1, 135.8, 136.3, 139.2, 143.5, 144.3,
147.1, 147.8; HRMS (ESI): calculated for C19H16NS2, 322.0719
(MH+); found: m/z, 322.0716.
4-Chloro-4″-fluoro-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3r)
Yield: 75% (146 mg); white solid; mp: 135–137 °C; IR (KBr): 4′-Methoxy-3-(methylthio)-5-(thiophen-2-yl)-[1,1′-biphenyl]-2-
2215 cm−1 1H NMR (400 MHz, CDCI3): δ 1.68–1.72 (m, 2H, carbonitrile (5c)
;
–CH2), 1.85–1.91 (m, 4H, –CH2), 3.30–3.33 (m, 4H, –CH2), 7.19
(s, 2H, ArH), 7.21–7.24 (m, 2H, ArH), 7.48 (d, J = 8 Hz, 2H,
ArH), 7.57–7.61 (m, 4H, ArH); 13C NMR (100 MHz, CDCl3): δ
24.1, 26.2, 53.7, 104.5, 115.7 (d, JC–F = 20 Hz), 116.1, 118.0,
121.2, 128.6, 129.3, 130.7 (d, JC–F = 10 Hz), 134.8, 138.3, 144.9,
147.0, 158.8, 163.0 (d, JC–F = 250 Hz); HRMS (ESI): calculated
for C24H21ClFN2, 391.1372 (MH+); found: m/z, 391.1371.
Yield: 38% (64 mg); white solid; mp: 116–118 °C; IR (KBr):
1
2216 cm−1; H NMR (400 MHz, CDCI3): δ 2.65 (s, 3H, –SMe),
3.87 (S, 3H, –OMe), 7.02 (d, J = 8 Hz, 2H, ArH), 7.13 (t, J =
12 Hz, 1H, ArH), 7.40–7.44 (m, 4H, ArH), 7.52 (d, J = 8 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3): δ 16.2, 55.5, 104.2, 114.2,
115.4, 117.1, 121.6, 127.3, 127.8, 128.1, 129.5, 132.1, 138.6,
139.3, 144.6, 148.4, 164.6; HRMS (ESI): calculated for
C19H16NOS2, 338.0668 (MH+); found: m/z, 338.0670.
4″-Bromo-4-chloro-5′-(piperidin-1-yl)-[1,1′:3′,1″-terphenyl]-4′-
carbonitrile (3s)
3-(Methylthio)-5-(thiophen-2-yl)-[1,1′-biphenyl]-2-carbonitrile
(5d)
Yield: 76% (171 mg); white solid; mp: 130–132 °C; IR (KBr):
2215 cm−1 1H NMR (400 MHz, CDCI3): δ 1.59–1.64 (m, 2H, Yield: 35% (54 mg); white solid; mp: 122–124 °C; IR (KBr):
;
–CH2), 1.77–1.80 (m, 4H, –CH2), 3.23 (t, J = 12 Hz, 4H, –CH2), 2214 cm−1; H NMR (400 MHz, CDCI3): δ 2.65 (s, 3H, –SMe),
7.10 (d, J = 4 Hz, 2H, ArH), 7.41(d, J = 8 Hz, 4H, ArH), 7.5 (d, 7.13–7.15 (m, 1H, ArH), 7.41–7.42 (m, 1H, ArH), 7.44–7.46 (m,
J = 8 Hz, 2H, ArH), 7.59 (d, J = 8 Hz, 2H, ArH); 13C NMR 4H, ArH), 7.47–7.52 (m, 2H, ArH), 7.56–7.58 (m, 2H, ArH); 13C
(100 MHz, CDCl3): δ 24.0, 26.0, 53.5, 104.2, 116.2, 117.7, 121.0, NMR (100 MHz, CDCl3): δ 16.4, 106.7, 115.6, 126.4, 127.5,
123.1, 128.5, 129.1, 130.4, 131.7, 134.7, 137.6, 138.1, 145.0, 127.9, 128.2, 128.4, 129.0, 129.5, 130.1, 134.2, 137.0, 139.0,
146.7, 158.7; HRMS (ESI): calculated for C24H21BrClN2, 139.2, 148.8; HRMS (ESI): calculated for C18H14NS2, 308.0562
1
451.0571 (MH+); found: m/z, 451.0549.
(MH+); found: m/z, 308.0561.
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Paper
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Conclusions
In summary, we developed a simple, efficient and new syn-
thetic approach for obtaining functionalized meta-teraryls in
good yields through the carbanion-induced ring transform-
ation of 2H-pyran-2-ones. We have also extended the appli-
cation of this methodology for the synthesis of 2,4-diaryl-
6-(methylthio)benzonitriles which can further undergo C–S
bond cleavage and coupling with boronic acid to provide triar-
ylbenzene. We also found that among various possible
mechanistic pathways, this reaction exclusively provides m-ter-
aryls regioselectively. It is also understood that compound 2
have the same structural features as allyl cyanide and 2-cyano-
methylbenzonitrile but behave differently under basic con-
ditions. We have successfully achieved methylsulfanyl group
containing benzene, which was not possible earlier via ring
transformation reaction. The reactions were operated under
simple and mild conditions.
Conflicts of interest
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Chem. Soc., 2005, 127, 11614.
There are no conflicts to declare.
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Acknowledgements
RP and S thank the UGC, New Delhi and RS thanks the CSIR,
New Delhi for providing research fellowships. AE thanks the
DBT-TWAS for the SRF research fellowship. RP thanks the
ICMR, New Delhi (BIC/12(03)/2014), CSIR, New Delhi (No. 02
(0286)/16/EMR-II) and the DST New Delhi (Purse grant) for
research funding. USIC, Delhi University is acknowledged for
instrumentation facility.
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