AMVN-initiated expedient synthesis of biaryls by the coupling reaction of unactivated arenes and heteroarenes with aryl iodides

Article abstract of DOI:10.1039/c3nj01105d

The role of radical initiators AMVN and AIBN has been studied in the potassium tert-butoxide mediated biaryl coupling reaction of aryl iodides with unactivated arenes. Radical initiator AMVN promoted carbon-carbon bond formation expeditiously from aryl iodide having various groups such as amino, methoxy, fluoro, methyl, and trifluoromethyl and arenes in the presence of potassium tert-butoxide (4 equiv.) at 110 °C in 2-5 h. Substituted arenes such as toluene, xylene, anisole, and fluorobenzene also proceeded to form biaryls under AMVN-initiated reaction conditions. Moreover naphthalene, pyridine, pyrimidine, and pyridazine also coupled with aryl iodides and produced biaryls in 41-82% yields. It seems that AMVN initiates the formation of the aryl radical, which enters the radical chain reaction. The generated aryl radical may combine with the arene leading to a biaryl radical, which upon protonation gives the biphenyl radical anion and tert-butanol. The biphenyl radical anion finally reacts with the aryl iodide generating the aryl radical and thus completes the radical chain reaction with concomitant release of biphenyl.

Full text of DOI:10.1039/c3nj01105d

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AMVN-initiated expedient synthesis of biaryls by
the coupling reaction of unactivated arenes and
heteroarenes with aryl iodides†
Cite this: New J. Chem., 2014,
38, 827
Bhagat Singh Bhakuni, Abhimanyu Yadav, Shailesh Kumar and Sangit Kumar*
The role of radical initiators AMVN and AIBN has been studied in the potassium tert-butoxide mediated
biaryl coupling reaction of aryl iodides with unactivated arenes. Radical initiator AMVN promoted
carbon–carbon bond formation expeditiously from aryl iodide having various groups such as amino,
methoxy, fluoro, methyl, and trifluoromethyl and arenes in the presence of potassium tert-butoxide
(4 equiv.) at 110 1C in 2–5 h. Substituted arenes such as toluene, xylene, anisole, and fluorobenzene
also proceeded to form biaryls under AMVN-initiated reaction conditions. Moreover naphthalene,
pyridine, pyrimidine, and pyridazine also coupled with aryl iodides and produced biaryls in 41–82% yields.
It seems that AMVN initiates the formation of the aryl radical, which enters the radical chain reaction.
The generated aryl radical may combine with the arene leading to a biaryl radical, which upon protona-
tion gives the biphenyl radical anion and tert-butanol. The biphenyl radical anion finally reacts with the
aryl iodide generating the aryl radical and thus completes the radical chain reaction with concomitant
release of biphenyl.
Received (in Montpellier, France)
15th September 2013,
Accepted 9th December 2013
DOI: 10.1039/c3nj01105d
www.rsc.org/njc
A. Introduction
Biaryls are the privileged cores present in many pharmaceuticals,
natural products, agrochemicals and related organic molecules.
As a result synthesis of biaryls has attracted considerable interest
in academia and industry. Several methodologies have been
developed to construct biaryls in the last hundred years. Transi-
tion metal catalysts, particularly palladium-based catalysts, are
employed for the synthesis of biaryls. However, due to the high
cost of palladium, Pd-free methods have attracted considerable
interest for the synthesis of biaryls in recent times. Biaryl
coupling promoted by tert-butoxide together with the ligand is
of particular interest as unactivated arenes can be coupled with
an aryl anion radical without adding any palladium or transition
metal catalyst.
Scheme 1 Coupling of the aryl radical anion with benzene.
Shi et al., and others have exploited KOtBu in various inter- and
intramolecular carbon–carbon coupling reactions and the role of
KOtBu in the carbon–carbon bond formation is unambiguously
established.2–5 Very recently light stimulated biaryl synthesis has
been established by Rossi et al. and Li et al.6c,d,7 It is widely
established that the KOtBu mediated carbon–carbon coupling
reaction proceeds by a single electron transfer (Scheme 1).6a,b
The role of radical initiators has not been explored in the
KOtBu-mediated intermolecular biaryl coupling reaction. Here
a KOtBu-mediated biaryl coupling of unactivated arenes with
aryl iodides in the presence of an alkyl diazo radical initiator
(E)-2,20-(diazene-1,2-diyl)bis(2,4-dimethylpentanenitrile) (AMVN)
is presented.
For the first time Itami et al. have presented KOtBu mediated
synthesis of hetero-biaryls by coupling heteroarenes with aryl
halides under microwave heating conditions. However, the same
reaction requires 13 h for completion at 120 1C under conven-
tional heating conditions.1a Kwong and Lei et al., Hayashi et al.,
Department of Chemistry, Indian Institute of Science Education and Research
(IISER) Bhopal, Indore By-pass Road, Bhauri, Bhopal, Madhya Pradesh, 462 066,
India. E-mail: sangitk@gmail.com, sangitkumar@iiserb.ac.in; Web: http://home.
iiserbhopal.ac.in/~sangitkumar; Fax: +91-755-669-2392; Tel: +91-755-669-2326
† Electronic supplementary information (ESI) available: NMR (1H, 13C, and
13C-DEPT-135) spectra of biaryls 1–40 and EPR spectra of the reaction mixture.
See DOI: 10.1039/c3nj01105d
B. Results and discussion
We began the control experiment of the KOtBu mediated biaryl
coupling using 4-iodoanisole as an iodoarene substrate for the
optimization of reaction conditions (Table 1). Potassium tert-
butoxide alone is found to be ineffective for the biaryl coupling
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Table 1 Optimization of reaction conditionsa
Table 2 AMVN-initiated biaryl synthesis
Entry
Ar–I
Biaryl
t (h)
Yielda (%)
Initiator/Lb
Solvent
Time (h)
Yield 1 (%)
1
3
1 (87)
Entry
2
3
24
6
2 (96)
2 (85)b
2 (68)c
1
—
AMVN
AIBN
AMVN
AMVN
AMVN
AMVN
Bathophene
Bathocuproine
Phenanthroline
TMEDA
Bipyridyl
Benzene
Benzene
Benzene
Benzene
Benzene
DMF
24
3
20
3
3
3
3
20
20
24
24
24
Trace
87
30
66
49
12
32
—
3b
4c
2c
3
4d
5e
6f
7f
8
5
6
3
3
3 (84)
4 (71)
tBuOH
Benzene
Benzene
Benzene
Benzene
Benzene
9
13
48
—
10
11
12
7
3
3
3
3
5 (77)
6 (75)
7 (80)
8 (65)
7
a
Reaction was carried out at the 1 mmol scale using 4-iodoanisole and
4 equiv. of KOtBu in 3 mL of benzene. 20 mol% of the initiator/ligand
b
was used. 4, 3, and 2 equiv. of KOtBu was used. 4, 3, and 2 equiv. of
c
d
8
KOtBu was used. 4, 3, and 2 equiv. of KOtBu was used. Reaction was
carried out using 10 mmol of benzene when DMF or tBuOH (3 mL) was
used as solvent in a sealed tube.
e
f
9
reaction as only traces of biaryl 1 were observed in the absence
of a radical initiator (entry 1, Table 1). AMVN yielded coupled
product 1 in 87% yield in 3 h (entry 2, Table 1). Azoiso-
butrylonitrile (AIBN) was found to be a poor initiator for the
formation of biaryl 1. Further, we screened DMF and tert-
butanol as solvents in the biaryl coupling reaction. Both
solvents yielded biphenyl 1 in 12 and 32% yields, respectively
(entries 6 and 7, Table 1). Other ligands such as phenanthroline,
bathophen, bipyridyl, and tetramethylethylenediamine (TMEDA)
in the KOtBu-mediated coupling reaction are compared with the
AMVN radical initiator. None of the ligand provided good yield
of biaryl 1 under our reaction conditions (entries 8–12, Table 1).
After studying the role of radical initiators and ligands,
substrate scope was explored in the presence of AMVN initiated
coupling reaction and results are summarized in Table 2.
4-Iodoanisole coupled with benzene and produced methoxy
biphenyl 1 in 87% yield. Next, iodobenzene was coupled with
benzene under optimized reaction conditions. Indeed, biaryl 2
was obtained in 96% yield in 3 h (entry 2, Table 2). It is worth
mentioning that biaryl 2 was obtained in 60–85% yields in
various ligands catalyzed reactions.1,2 Here biphenyl 2 was not
only obtained in excellent yield but also biaryl 2 has been
10
11
12
13
2
3
3
9 (91)
10 (85)
11 (86)
14
3
3
12 (89)
13 (83)
15
a
Yields were obtained using AMVN, please see the Experimental
b
section for more details. Reaction was carried out at the 49 mmol
scale under reflux conditions. Yield obtained from bromobenzene.
c
synthesized at the 45 mmol scale under conventional reflux in the potassium tert-butoxide-mediated biphenyl synthesis
conditions (entry 3, Table 2). Bromobenzene underwent aryl- despite having further synthetic utilities of amino or nitro
ation in a similar manner to iodobenzene albeit it gave 68% groups in functional group transformations and agrochemicals.8,9
yield of 2 (entry 4, Table 2). Chlorobenzene was noticed to be Here 1-iodo-2-nitrobenzene and 1-iodo-2-aminobenzene were suc-
sluggish and poor yield (9%) of biaryl 2 was obtained. Next cessfully utilized for the synthesis of amino and nitro-substituted
substituted iodobenzenes were explored in the AMVN-initiated biphenyls 8 and 9 (entries 10 and 11, Table 2). Furthermore,
biaryl coupling reaction. Iodobenzenes having electron donat- iodo-heteroarenes such as iodo-pyridine, iodo-thiophene, and
ing CH3, OCH3, and NH2 or electron withdrawing F, CF3, and iodo-naphthalene were amenable to the reaction conditions
NO2 groups underwent coupling reaction successfully and and respective biaryls 10–13 were obtained in 70–89% yields
yielded respective biaryls 2–9 in 3–4 h (entries 5–11, Table 2). (entries 12–15, Table 2).
Iodoarenes with various functional groups have been exploited
After successful arylation of benzene, substituted benzenes
under KOtBu-mediated biaryl coupling reactions.1,2 However, were explored under optimized reaction conditions (Scheme 2).
ortho-nitro and ortho-amino aryliodides have not been used Electron rich para-xylene, toluene, anisole coupled with iodobenzene
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Table 3 Coupling of heteroarenes with aryl iodides
Entry
1
Arene
Biaryla (ratio)
Position-(yield%)
10 2-(55)
11 3-(19)
23 4-(13)
Scheme 2 Arylation in substituted arenes.
24 2-(64)
25 3-(18)
2
3
and para-methoxyiodobenzene underwent AMVN initiated carbon–
carbon coupling and gave biaryls 14, 18–20 in 71–75% yields.
Electron poor fluorobenzene also showed compatibility with
electron rich para-methoxyiodobenzene and ortho-amino/nitro
iodobenzenes leading to fluoro substituted biaryls 15–17 in
moderate to good yields. Naphthalene coupled with iodobenzene
and para-methoxy iodobenzene, however, low yields (41–45%) of
1/2-phenylnaphthyls 21 and 22 were obtained.
26 2-(50)
27 3-(16)
28 4-(11)
29 2-(44)
30 3-(31)
4
To further extend the scope of carbon–carbon coupling
reaction, the coupling reactions of heteroarenes such as pyridine,
pyrimidine, and pyridazine were explored with various aryl
iodides (Table 3).
5
6
31 R0 = H (55)
32 R0 = OCH3 (73)
33 2-Ph (18)
34 4-Ph (8)
35 5-Ph (12)
36 6-Ph (22)
Pyridines coupled smoothly with 4-methyl, 4-methoxy, and
2-methoxy iodobenzenes under reaction conditions with the
complete conversion of aryl iodides. Pyridine gave a mixture of
regioisomers 10, 11, and 23 in a 4.5 : 1.3 : 1 ratio when reacted
with iodobenzene (entry 1, Table 3). The regioselective outcome
and yield remained nearly the same when para-methyl iodo-
benzene was used as a coupling substrate with pyridine and
2-substituted coupled product 24 was observed in a maximum
ratio as compared to isomer 25 (entry 2, Table 3). A similar
observation was made when 4-methoxy iodobenzene was used
as a coupling partner (entry 3, Table 3). On the other hand,
2-methoxy iodobenzene gave a poor ratio (1.5 : 1) of 2- and
3-regioisomers 29 and 30 presumably due to steric hindrance
between the methoxy substituent and the nitrogen atom (entry 4,
Table 3). Substituted 4-methoxy pyridine also coupled with
iodobenzene and 4-methoxy iodobenzene to give biaryls 31
and 32 in 55 and 77% yields, respectively, and 2-position
regioisomers were obtained as the major products (entries 5
and 6, Table 3). On the other hand, b-picoline gave a mixture of
all four possible regioisomers 33–36 in 60% overall yield (entry 7,
Table 3). Other heteroarenes such as pyrimidine and pyridazine
were also reacted with 4-iodotoluene to give 4-tolylpyrimidines
37–39 and 4-tolylpyridazines 40–41, respectively, in 68–76%
yields (entries 8 and 9, Table 3).
7
8
37 2-(32)
38 and 39
4- and 5-(44)b
40 4-(68)
41 3-(trace)
9
a
b
Ratio of isomers is based on the isolated yields. Combined yield of
38 and 39.
Mechanistic investigation
Several control experiments were carried out to understand the
role of AMVN in the biaryl coupling reaction and also the
electro-paramagnetic resonance (EPR) spectrum of the reaction
mixture was recorded. The EPR spectrum shows a single peak,
suggesting the involvement of radicals in the KOtBu-mediated Scheme 3 Mechanism for AMVN-initiated C–H arylation.
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biaryl coupling (EPR is described in the ESI,† pp. S37–S38).
4-Methoxybiphenyl (1).2a 4-Iodo anisole (232 mg, 0.99 mmol),
A reaction between iodobenzene and benzene was studied in potassium tert-butoxide (440 mg, 3.9 mmol), and AMVN
the presence of AMVN without adding KOtBu which failed to (52 mg, 0.21 mmol) were added into benzene (3 mL) in a sealed
provide biaryl 2. Similarly, potassium tert-butoxide alone is not tube. The white coloured reaction mixture was heated at
effective for the promotion of carbon–carbon coupling (entry 1, 110 1C for 3 h. After this, the reaction mixture was poured over
Table 1) which suggests that KOtBu and AMVN are required for water (50 mL), extracted with ethyl acetate (25 mL ꢁ 3), dried
carbon–carbon bond formation from iodobenzene and benzene. over Na2SO4, and concentrated on a rotary evaporator. The
The radical initiator presumably initiates the generation of aryl resultant white solid was purified by column chromatography
radical I (Scheme 3).
using hexane over silica gel. Yield 0.16 g (87%), 1H NMR
Based on the reported hypothesis,6 it is reasonable to (400 MHz, CDCl3) d 7.53 (t, J = 8.0 Hz, 4H), 7.40 (t, J = 8.0 Hz,
assume that generated phenyl radical I reacts with benzene 2H), 7.29 (t, J = 8.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 2H), 3.84 (s, 3H).
and could produce biphenyl radical II which may further react 13C NMR (100 MHz, CDCl3) d 159.2, 140.8, 133.8, 128.7, 128.2,
with KOtBu and generate biphenyl radical anion III. The 126.8, 126.7, 114.2, 55.4. GCMS (ESI) m/z 184.0, calcd for
biphenyl radical anion III may react with iodobenzene to give
desired biphenyl 2 with concomitant release of aryl radical I
and thus completes the radical chain.
C
13H12O: 184.0.
Synthesis of biaryls: biphenyl (2).2a Iodobenzene (206 mg,
1.01 mmol), potassium tert-butoxide (450 mg, 4.01 mmol), and
azomethylvaleronitrile (AMVN) (49 mg, 0.2 mmol) were added
into benzene (3 mL) in a sealed tube. The white coloured
reaction mixture was heated at 110 1C for 3 h. The progress
of the reaction was monitored by TLC. After this, the reaction
mixture was poured into water, extracted with ethyl acetate,
(25 mL ꢁ 3), dried over Na2SO4, and concentrated on a rotary
evaporator. The resultant white solid was purified by column
chromatography using hexane over silica gel. Yield 0.15 g
(96%). 1H NMR (400 MHz, CDCl3) d 7.59 (d, J = 8.0 Hz, 4H),
7.43 (t, J = 8.0 Hz, 4H), 7.34 (t, J = 8.0 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d 141.3, 128.0, 127.2, 127.3. GCMS (ESI)
m/z 154.1, calcd for C12H10: 154.1.
Conclusions
In summary, AMVN initiated synthesis of biaryls from aryl
iodides and arenes has been achieved by utilizing potassium
tert-butoxide base in short reaction time (3–8 h). Synthesis of
biphenyl 2 under conventional reflux conditions and at the
49 mmol scale suggests that biaryls could be accessed at a
multi-gram scale under conventional reflux conditions. The
presented methodology tolerates various functional groups
such as methoxy, methyl, fluoro, and trifluoromethyl in aryl-
iodides. Moreover, tolerance for ortho-nitro and ortho-amino
functionalities demonstrated further utility of the developed
methodology in the synthesis of nitro/amino-substituted biphenyls.
In addition, the AMVN initiated biaryl coupling also shows
amenability to the heteroarenes: pyridines, pyrimidine, and
pyridazine which may have numerous applications in pharma-
ceuticals and agrochemicals.8,9
Synthesis of biphenyl (2) from bromobenzene. Reaction
was carried out at the 1 mmol scale using bromobenzene
by following the similar procedure as described for iodo-
benzene. The reaction mixture was heated for 8 h. Yield
105 mg (68%).
Synthesis of biphenyl (2) at the 49 mmol scale under
refluxing conditions. Iodobenzene (9.99 g, 49 mmol) and KOtBu
(21.99 g, 196 mmol) were added to a single neck (500 mL) flask
containing 130 mL of benzene. After this, AMVN (2.43 g,
9.8 mmol) was added to the reaction mixture. In a reaction
C. Experimental section
General syntheses
All NMR experiments were carried out using a 400 MHz spectro- flask fitted with a reflux condenser under N2 the reaction
meter in CDCl3 and NMR chemical shifts are reported in ppm mixture was refluxed for 24 h at 110 1C. Standard workup and
referenced to the solvent peaks of CDCl3 at 7.26 ppm for 1H and purification yielded 6.414 g (85%) of biphenyl 1.
77.16 (ꢀ0.06) ppm for 13C, respectively. High resolution mass
4-Methyl-1,10-biphenyl (3).2a 4-Iodo toluene (218 mg,
analysis is performed on a quadruple-time of flight (Q-TOF) 1.0 mmol), potassium tert-butoxide (450 mg, 4.01 mmol), and
mass spectrometer equipped with an ESI source (+ve). Benzene, AMVN (52 mg, 0.21 mmol) were added into benzene (3 mL) in a
xylene, toluene, anisole and mesitylene were dried over calcium sealed tube. The white coloured reaction mixture was heated at
hydride. Arenes, aryl iodides, and azoisobutrylonitrile (AIBN) 110 1C for 3 h. After this, the reaction mixture was poured
were purchased from Sigma-Aldrich. Potassium tert-butoxide over water (50 mL), extracted with ethyl acetate (25 mL ꢁ 3),
(KOtBu), 97% purity, was purchased from SpectroChem, India dried over Na2SO4, and concentrated over a rotary evaporator.
and stored in desiccators. Anhydrous DMF and DMSO were This resulted in a colourless semi-solid, which was purified
obtained from Sigma-Aldrich with sure seal septa. Azomethyl- by column chromatography using hexane over silica gel.
1
valeronitrile (AMVN) was purchased from Hubei Datong Bio- Yield 0.142 g (84%), H NMR (400 MHz, CDCl3) d 7.57 (d, J =
Chemical Technology Co. Ltd., China. Silica gel (100–200 mesh 4.0 Hz, 2H), 7.49 (d, J = 4.0 Hz, 2H), 7.42 (t, J = 6.0 Hz, 2H),
size) was used for column chromatography. TLC analysis of 7.32 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 4.0 Hz, 2H), 2.39 (s, 3H).
reaction mixtures was performed using silica gel plates. Sealed- 13C NMR (100 MHz, CDCl3) d 141.2, 138.4, 137.0, 129.5, 128.7,
tubes were purchased from Aldrich. All the reactions were 127.0, 126.98, 126.97, 21.1. GCMS (ESI) m/z 168.1, calcd for
performed in hood otherwise stated.
C13H12: 168.1.
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1,10-4-(Trifluoromethyl)-biphenyl (4).6c 1-Iodo-4-(trifluoro- Yield 0.109 g (65%), 1H NMR (400 MHz, CDCl3) d 7.44
methyl)benzene (274 mg, 1.01 mmol), potassium tert-butoxide (t, J = 2.0 Hz, 3H), 7.36–7.31 (m, 2H), 7.16–7.11 (m, 2H), 6.81
(450 mg, 4.01 mmol) and AMVN (52 mg, 0.21 mmol) were added (t, J = 8.0 Hz, 1H), 6.76 (d, J = 4.0 Hz, 1H), 3.72 (bs, 2H). 13C NMR
into benzene (3 mL) in a sealed tube. The white coloured (100 MHz, CDCl3) d 143.5, 139.5, 130.5, 129.1, 128.8, 128.5,
reaction mixture was heated at 110 1C. The progress of the 127.7, 127.2, 118.6, 115.6. HRMS (ESI) m/z 170.0980, calcd for
reaction was monitored by TLC. The reaction mixture was
C
12H11N + H+: 170.0964.
heated for 4 h. Standard workup and purification gave 157 mg
2-Nitro-1,10-biphenyl (9).11 2-Iodo nitrobenzene (251 mg,
1
(71%) of biphenyl 4 as a semisolid. H NMR (400 MHz, CDCl3) 1.01 mmol), potassium tert-butoxide (556 mg, 4.02 mmol),
d 7.68 (bs, 4H), 7.59 (d, J = 6.0 Hz, 2H), 7.46 (t, J = 8.0 Hz, 2H), and AMVN (51 mg, 0.21 mmol) were added into benzene (3 mL)
7.40 (t, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 144.0, 139.8, in a sealed tube. The white coloured reaction mixture was heated
129.0, 128.2, 127.4, 127.3, 125.73, 125.7, 122.8.
at 110 1C for 2 h. Standard workup resulted in yellow oil which
2-Methoxy-1,10-biphenyl (5).2a 2-Iodo anisole (234 mg, was purified by column chromatography using hexane over silica
1.0 mmol), potassium tert-butoxide (460 mg, 4.1 mmol) and gel. Yield 0.181 g (91%), 1H NMR (400 MHz, CDCl3) d 7.84 (d, J =
AMVN (48 mg, 0.19 mmol) were added into benzene (3 mL) in a 4.0 Hz, 1H), 7.60 (tt, J = 8.0, 1.0 Hz, 1H), 7.48 (d, J = 4.0 Hz, 1H),
sealed tube. The white coloured reaction mixture was heated at 7.42 (t, J = 4.0 Hz, 4H), 7.32 (d, J = 2.0 Hz, 1H), 7.30 (d, J = 2.0 Hz,
110 1C. The progress of the reaction was monitored by TLC. The 1H). 13C NMR (100 MHz, CDCl3) d 137.4, 136.4, 132.3, 132.0,
reaction mixture was heated for 3 h. Standard workup and 128.7, 128.3, 128.2, 127.9, 127.1, 124.1. GCMS (ESI) m/z 199.0,
purification gave biphenyl 5 as a solid. Yield 0.141 g (77%), calcd for C12H9NO2: 199.0.
1H NMR (400 MHz, CDCl3) d 7.53 (d, J = 4.0 Hz, 2H), 7.47 (t, J =
2-Phenylpyridine (10).1a,5b 2-Iodopyridine (206 mg, 1.01 mmol),
8.0 Hz, 2H), 7.38 (t, J = 8.0 Hz, 3H), 7.10 (d, J = 6.0 Hz, 1H), 7.04 potassium tert-butoxide (550 mg, 4.9 mmol), and AMVN (72.0 mg,
(d, J = 4.0 Hz, 1H). 3.85 (s, 3H). 13C NMR (100 MHz, CDCl3) 0.25 mmol) were added into benzene (3 mL) in a sealed tube.
d 156.6, 138.7, 131.0, 130.8, 129.6, 128.7, 128.1, 127.0, 120.9, The white coloured reaction mixture was heated at 110 1C for
111.3, 55.6. GCMS (ESI) m/z 184.0, calcd for C13H12O: 184.1.
3 h. After this, the reaction mixture was poured over water
2-Methyl-1,10-biphenyl (6).2a 2-Iodo toluene (221 mg, 1.01 mmol), (50 mL), extracted with ethyl acetate, (25 mL ꢁ 3), dried over
potassium tert-butoxide (456 mg, 4.02 mmol), and AMVN Na2SO4, and concentrated over a rotary evaporator. This
(54 mg, 0.22 mmol) were added into benzene (3 mL) in a sealed resulted in colourless oil which was purified by column
tube. The white coloured reaction mixture was heated at 110 1C chromatography using hexane–EtOAc (9 : 1) over silica gel. Yield
1
for 3 h. Standard workup and purification gave colourless 0.132 g (85%) H NMR (400 MHz, CDCl3) d 8.69 (d, J = 2.0 Hz,
liquid of 6. Yield 0.126 g (75%), 1H NMR (400 MHz, CDCl3) 1H), 7.98 (d, J = 4.0 Hz, 2H), 7.76–7.70 (m, 2H), 7.47 (t, J =
d 7.40 (t, J = 8.0 Hz, 2H), 7.32 (q, J = 7.0 Hz, 3H), 7.26–7.22 8.0 Hz, 2H), 7.40 (t, J = 6.0 Hz, 1H), 7.21 (t, J = 8.0, 0.5 Hz, 1H).
(m, 4H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3) d 141.97, 13C NMR (100 MHz, CDCl3) d 157.4, 149.6, 139.3, 136.8, 129.0,
141.94, 135.4, 130.3, 129.8, 129.2, 128.1, 127.2, 126.8, 125.8, 128.8, 127.0, 122.1, 120.6. HRMS (ESI) m/z 156.0819 (calcd for
20.5. GCMS (ESI) m/z 168.1, calcd for C13H12: 168.1.
C
11H9N + H: 156.0808).
3-Methyl-1,10-biphenyl (7).2a 3-Iodo toluene (220 mg,
3-Phenylpyridine (11).1a,5b Reaction was carried out at the
1.1 mmol), potassium tert-butoxide (448 mg, 5.0 mmol) and 1 mmol scale using 3-iodopyridine (205 mg, 1.0 mmol), potas-
AMVN (49 mg, 0.2 mmol) were added into benzene (3 mL) in a sium tert-butoxide (440 mg, 3.99 mmol), and AMVN (52 mg,
sealed tube. The white coloured reaction mixture was heated 0.21 mmol), which were added into benzene (3 mL) in a sealed
at 110 1C for 3 h. Standard workup gave colourless liquid, tube. Yield 0.133 g (86%), 1H NMR (400 MHz), 1H NMR
which was purified by column chromatography using hexane (400 MHz, CDCl3) d 8.84 (d, J = 1.0 Hz, 1H), 8.58 (d, J =
1
over silica gel. Yield 0.134 g (80%), H NMR (400 MHz, CDCl3) 4.0 Hz, 1H), 7.86 (td, J = 4.0, 1.0 Hz, 1H), 7.57 (d, J = 4.0 Hz,
d 7.60 (d, J = 4.0 Hz, 2H), 7.43 (q, J = 8.0 Hz, 4H), 7.34 (t, J = 2H), 7.47 (t, J = 4.0 Hz, 2H), 7.40 (d, J = 4.0 Hz, 1H), 7.35 (q, J =
6.0 Hz, 2H), 7.18 (d, J = 4.0 Hz, 1H), 2.44 (s, 3H). 13C NMR 4.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 148.5, 148.3, 137.9,
(100 MHz, CDCl3) d 141.4, 141.3, 138.4, 128.7, 128.69, 128.03, 136.7, 134.5, 129.1, 128.1, 127.2, 123.6. HRMS (ESI) m/z
128.01, 127.2, 127.19, 124.3, 21.6. GCMS (ESI) m/z 168.0, calcd 156.0819, calcd for C11H9N + H: 156.0808.
for C13H12: 168.1.
2-Phenylthiophene (12).12 2-Iodothiophene (212 mg,
[1,10-Biphenyl]-2-amine (8).10 2-Iodo aniline (219 mg, 1.01 mmol), potassium tert-butoxide (461 mg, 4.1 mmol), and
1.0 mmol), potassium tert-butoxide (447 mg, 3.99 mmol) and AMVN (33 mg, 0.20 mmol) were added into benzene (6 mL) in a
AMVN (57 mg, 0.23 mmol) were added into benzene (3 mL) in a sealed tube. The white coloured reaction mixture was heated at
sealed tube. The white coloured reaction mixture was heated at 110 1C. The progress of the reaction was monitored by TLC. The
110 1C. The progress of the reaction was monitored by TLC. The reaction mixture was heated for 3 h. After this, the reaction
reaction mixture was heated for 3 h. After this, the reaction mixture was poured over water (70 mL), extracted with ethyl
mixture was poured into a saturated solution of sodium acetate, (25 mL ꢁ 3), dried over Na2SO4, and concentrated over
bicarbonate, extracted with ethyl acetate, (25 mL ꢁ 3), dried over a rotary evaporator, to result in colourless oil which was
Na2SO4, and concentrated on a rotary evaporator. The resultant purified by column chromatography using hexane over silica
colourless semi-solid was purified by column chromato- gel. Yield 0.142 g (89%), 1H NMR (400 MHz, CDCl3) d 7.60
graphy using a 9 : 1 mixture of hexane : EtOAc over silica gel. (d, J = 4.0 Hz, 2H), 7.37 (d, J = 6.0 Hz, 2H), 7.31–7.26 (m, 3H),
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7.07 (q, J = 7.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 144.5, hexane : EtOAc over silica gel. In this case, para isomer 8 was
134.4, 128.9, 127.5, 126.0, 124.8, 123.1. GCMS (ESI) m/z 160.0, observed as a major product and other isomers could not be
calcd for C10H8S: 160.0.
isolated/detected. Yield 0.103 g (55%). 1H NMR (400 MHz,
1-Phenylnaphthalene (13).2a 1-Iodonaphthalene (256 mg, CDCl3) d 7.44–7.34 (m, 3H), 7.18–7.09 (m, 3H), 6.81 (t, J =
1.01 mmol), potassium tert-butoxide (451 mg, 5.01 mmol), 8.0 Hz, 1H), 6.75 (d, J = 4.0 Hz, 1H), 3.74 (bs, 2H). 13C NMR
and AMVN (47 mg, 0.19 mmol) were added into benzene (100 MHz, CDCl3) d 130.5, 130.4, 130.3, 129.2, 129.1, 129.0,
(3 mL) in a sealed tube. The white coloured reaction mixture 128.8, 128.5, 124.8, 118.7, 116.2, 115.8, 115.6, 114.0, 113.5.
was heated at 110 1C for 3 h. After this, the reaction mixture was GCMS (ESI) m/z 187.1, calcd for C12H10FN: 187.1.
poured over water (70 mL), extracted with ethyl acetate,
2-Fluoro-40-methoxy-1,10-biphenyl and 4-fluoro-40-methoxy-
(25 mL ꢁ 3), dried over Na2SO4, and concentrated over a rotary 1,10-biphenyl (17).16 4-Iodo anisole (236 mg, 1.01 mmol), potassium
evaporator. The resultant residue was purified by column tert-butoxide (448 mg, 4.0 mmol), and AMVN (5.0 mg, 0.20 mmol)
chromatography using hexane over silica gel. Yield 0.169 g were added into fluorobenzene (3 mL) in a sealed tube. The
(83%), mp 240–242 1C. 1H NMR (400 MHz, CDCl3) d 7.90 white coloured reaction mixture was heated at 110 1C. The
(d, J = 4.0 Hz, 2H), 7.86 (d, J = 4.0 Hz, 1H), 7.54–7.47 (m, 6H), progress of the reaction was monitored by TLC. The reaction
7.45–7.40 (m, 3H). 13C NMR (100 MHz, CDCl3) d 140.8, 140.3, mixture was heated for 5 h. After this, the reaction mixture
133.8, 131.6, 130.1, 128.3, 127.2, 126.9, 126.04, 126.03, 125.8, was poured over water (70 mL), extracted with ethyl acetate
125.4. GCMS (ESI) m/z 204.0, calcd for C16H12: 204.0.
40-Methoxy-2,5-dimethyl-1,10-biphenyl (14).5b
(25 mL ꢁ 3), dried over Na2SO4, and concentrated over a rotary
1-Iodo-4- evaporator. The resultant white colourless liquid was purified
methoxybenzene (234 mg, 1.0 mmol), potassium tert-butoxide by column chromatography using hexane over silica gel. Yield
(480 mg, 4.2 mmol), and AMVN (58 mg, 0.22 mmol) were added 0.157 g (72%). 1H NMR (400 MHz, CDCl3) d 7.49 (t), 7.40 (t),
into para-xylene (3 mL) in a sealed tube. The white coloured 7.36–7.23 (m), 7.19–7.09 (m), 6.96 (m), 3.85 (s), 3.84 (s).
reaction mixture was heated at 110 1C. The progress of the 13C NMR (100 MHz, CDCl3) d 159.6, 159.2, 130.5, 130.49,
reaction was monitored by TLC. The reaction mixture was 130.2, 130.1, 128.4, 128.3, 128.2, 124.3, 124.28, 122.3, 116.2,
heated for 24 h. After this, the reaction mixture was poured 115.6, 114.3, 114.26, 113.9, 113.5, 113.4, 113.3, 55.4, 55.3.
over water (50 mL), extracted with ethyl acetate, (25 mL ꢁ 3), GCMS (ESI) m/z 202.1, calcd for C13H11FO + H: 202.1.
dried over Na2SO4, and concentrated over a rotary evaporator.
2-Methyl-20-nitro-1,10-biphenyl, 30-methyl-2-nitro-1,10-biphenyl,
The resultant semisolid was purified by column chromato- and 40-methyl-2-nitro-1,10-biphenyl (18).13 1-Iodo-2-nitrobenzene
graphy using hexane over silica gel. Yield 0.15 g (71%). (251 mg, 1.01 mmol), potassium tert-butoxide (448 mg, 4.0 mmol)
1H NMR (400 MHz, CDCl3) d 7.23 (d, J = 4.0 Hz, 2H), 7.13 (d, and, AMVN (56 mg, 0.22 mmol) were added into toluene (3 mL)
J = 4.0 Hz, 1H), 7.03 (d, J = 4.0 Hz, 2H), 6.93 (d, J = 4.0 Hz, 2H), in a sealed tube. The white coloured reaction mixture was
3.84 (s, 3H), 2.32 (s, 3H), 2.21 (s, 3H). 13C NMR (100 MHz, heated at 110 1C. The progress of the reaction was monitored
CDCl3) d 158.8, 141.4, 135.2, 134.5, 132.3, 130.6, 130.3, 130.2, by TLC. The reaction mixture was heated for 5 h. After this, the
127.7, 113.5, 55.3, 20.9, 20.0. GCMS (ESI) m/z 212.0, calcd for reaction mixture was poured over water (70 mL), extracted with
C
15H16O: 212.0.
ethyl acetate, (25 mL ꢁ 3), dried over Na2SO4, and concentrated
2-Fluoro-20-nitro-1,10-biphenyl and 40-fluoro-2-nitro-1,10- over a rotary evaporator. The resultant yellow oil was purified by
biphenyl (15).13,14 2-Iodo-nitrobenzene (252 mg, 1.01 mmol), column chromatography using hexane over silica gel. Yield
potassium tert-butoxide (452 mg, 4.01 mmol), and AMVN 0.16 g (75%), 1H NMR (400 MHz, CDCl3) d 7.98 (d), 7.81 (t),
(52 mg, 0.21 mmol) were added into fluorobenzene (3 mL) in 7.63–7.53 (m), 7.50 (t), 7.43 (t), 7.31–7.20 (m), 7.10 (t), 2.39 (s),
a sealed tube. The white coloured reaction mixture was heated 2.38 (s), 2.1 (s). 13C NMR (100 MHz, CDCl3) d 149.4, 149.3, 149.2,
at 110 1C. The progress of the reaction was monitored by TLC. 139.0, 138.4, 138.2, 138.1, 137.5, 137.3, 136.6, 136.5, 136.4,
The reaction mixture was heated for 5 h. Yield 0.157 g (72%). 136.3, 135.6, 134.4, 132.0, 131.95, 130.0, 129.5, 129.0, 128.98,
1H NMR (400 MHz, CDCl3) d 8.01 (d), 7.86 (t), 7.65 (t), 7.60 (t), 128.7, 128.6, 128.5, 128.3, 128.27, 128.2, 128.0, 127.9, 127.8,
7.55–7.45 (m), 7.44–7.21 (m), 7.12–7.02 (m). 13C NMR (100 MHz, 125.8, 125.0, 124.1, 124.0, 21.4, 21.3, 19.9. GCMS (ESI) m/z
CDCl3) d 164.0, 163.9, 163.5, 161.54, 161.47, 158.1, 149.1, 139.5, 213.0, calcd for C13H11NO2: 213.0.
135.3, 135.1, 132.4, 130.3, 129.8, 128.4, 124.8, 124.6, 124.2,
121.7, 115.6, 115.3, 115.1, 115.07. GCMS (ESI) m/z 217.0, calcd 1,10-biphenyl (19).6d Iodobenzene (204 mg, 1.0 mmol), potassium
for C12H8O2NF: 217.0. tert-butoxide (451 mg, 4.0 mmol), and AMVN (48 mg, 0.20 mmol)
2-Methoxy-1,10-biphenyl, 3-methoxy-1,10-biphenyl and 4-methoxy-
40-Fluoro-[1,10-biphenyl]-2-amine (16).15 2-Iodoaniline (221 mg, were added into anisole (3 mL) in a sealed tube. The white
1.01 mmol), potassium tert-butoxide (460 mg, 4.1 mmol), and coloured reaction mixture was heated at 110 1C for 10 h. After
AMVN (54 mg, 0.22 mmol) were added into benzene (3 mL) in a this, the reaction mixture was poured over water (70 mL),
sealed tube. The white coloured reaction mixture was heated extracted with ethyl acetate, (25 mL ꢁ 3), dried over Na2SO4,
at 110 1C for 3 h. After this, the reaction mixture was poured and concentrated over a rotary evaporator. The resultant colour-
into a saturated solution of sodium bicarbonate, extracted with less semi-solid was purified by column chromatography using
1
ethyl acetate (25 mL ꢁ 3), dried over Na2SO4, and concentrated hexane over silica gel. Yield 0.133 g (72%), H NMR (400 MHz,
on a rotary evaporator. The resultant colourless semisolid was CDCl3) d 7.59 (m), 7.53 (m), 7.40 (m), 7.32 (m), 7.19 (m),
purified by column chromatography using a 8 : 2 mixture of 7.13 (m), 7.03 (m), 6.98 (m), 3.86 (s), 3.85 (s), 3.80 (s).
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13C NMR (100 MHz, CDCl3) d 160.0, 159.2, 159.5, 142.8, 141.1, Two signals could not be detected in 13C NMR presumable
140.9, 138.6, 133.8, 130.9, 130.8, 129.8, 129.6, 128.8, 128.6, due to overlap of signals. GCMS (ESI) m/z 234.1 calcd for
128.2, 128.0, 127.4, 127.2, 126.9, 126.8, 126.7, 120.9, 119.7,
114.2, 113.9, 112.9, 112.7, 111.3, 55.6, 55.4, 55.3. GCMS (ESI)
m/z 184.0 calcd for C13H12O: 184.0.
C
17H14O: 234.1.
2-Phenylpyridine (10).1a,5b Iodobenzene (206 mg, 1.01 mmol),
potassium tert-butoxide (448 mg, 4.0 mmol), and AMVN (48 mg,
2,40-Dimethoxy-1,10-biphenyl and 3,40-dimethoxy-1,10-biphenyl 0.19 mmol) were added into pyridine (3 mL) in a sealed tube.
(20).5c 4-Iodo anisole (235 mg, 1.0 mmol) potassium tert- The white coloured reaction mixture was heated at 110 1C for
butoxide (458 mg, 4.0 mmol), and AMVN (52 mg, 0.21 mmol) 5 h. After this, the reaction mixture was poured over water
were added into anisole (3 mL) in a sealed tube. The white (70 mL), extracted with ethyl acetate (25 mL ꢁ 3), dried over
coloured reaction mixture was heated at 110 1C for 15 h. After Na2SO4, and concentrated over a rotary evaporator. The resul-
this, the reaction mixture was poured over water (150 mL), tant white colourless liquid which was purified by column
extracted with ethyl acetate, (25 mL ꢁ 3), dried over Na2SO4, chromatography using a 8 : 2 mixture of hexane : EtOAc over
and concentrated over a rotary evaporator. The resultant semi- silica gel yielded three fractions; (i) first fraction, yield 85 mg
solid was purified by column chromatography using hexane (55%). 1H NMR (400 MHz, CDCl3) d 8.69 (d, J = 2.0 Hz, 1H),
over silica gel. In this case, the meta-isomer was not observed 8.00 (d, J = 8.0 Hz, 2H), 7.76–7.70 (m, 2H), 7.47 (t, J = 8.0 Hz,
by 1H and 13C NMR spectroscopy. Yield 0.156 g (73%), 2H), 7.40 (t, J = 8.0 Hz, 2H), 7.23–7.19 (t, J = 8.0 Hz, 1H).
1H NMR (400 MHz, CDCl3) d 7.51 (m), 7.46 (m), 7.29 (m), 7.12 13C NMR (100 MHz, CDCl3) d 157.5, 149.7, 139.4, 136.7, 129.0,
(m), 7.07 (m), 7.00 (m), 6.95 (m), 6.84 (m), 3.84 (s), 3.838 (s), 128.8, 126.9, 122.1, 120.6. HRMS (ESI) m/z 156.0829, calcd for
3.831 (s), 3.80 (s). 13C NMR (100 MHz, CDCl3) d 159.9, 158.7,
158.65, 156.5, 133.5, 130.9, 130.7, 130.6, 130.4, 129.7, 128.2,
C
11H9N + H: 156.0808.
3-Phenylpyridine (11).1a,5b Second fraction, yield 30 mg
128.16, 127.7, 120.8, 119.3, 114.2, 113.5, 112.5, 112.0, 111.2, (19%). 1H NMR (400 MHz, CDCl3) d 8.84 (d, J = 2.0 Hz, 1H),
55.5, 55.4, 55.3, 55.27. GCMS (ESI) m/z 214.1 calcd for 8.57 (dd, J = 8.0, 2.0 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.56 (d, J =
C
14H14O2: 214.1.
8.0 Hz, 2H), 7.46 (t, J = 8.0 Hz, 2H), 7.40 (t, J = 8.0 Hz, 1H), 7.34
1-Phenylnaphthalene and 2-phenylnaphthalene (21).2a,6d (q, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 148.4, 148.3,
Iodobenzene (204 mg, 1.0 mmol), potassium tert-butoxide 137.8, 136.7, 134.4, 129.1, 128.1, 127.2, 123.6. GCMS (ESI) m/z
(460 mg, 4.02 mmol), and AMVN (48 mg, 0.19 mmol) were 155.0, calcd for C11H9N: 155.0.
added into naphthalene (128 mg, 1.0 mmol) in a sealed tube.
4-Phenylpyridine (23).1a,5b Third fraction, yield 20 mg (13%).
The white coloured reaction mixture was heated at 110 1C. The 1H NMR (400 MHz, CDCl3) d 8.64 (d, J = 8.0 Hz, 2H), 7.62 (d, J =
reaction mixture was heated for 8 h. After this, the reaction 8.0 Hz, 2H), 7.50–7.42 (m, 5H). 13C NMR (100 MHz, CDCl3)
mixture was poured over water (70 mL), extracted with ethyl d 150.1, 150.09, 148.5, 138.1, 129.1, 127.0, 121.7. GCMS (ESI)
acetate (25 mL ꢁ 3), dried over Na2SO4, and concentrated over a m/z 155.0, calcd for C11H9N: 155.0.
rotary evaporator. The resultant white colourless liquid was
2-(4-Methylphenyl)pyridine (24).5b 4-Iodotoluene (220 mg,
purified by column chromatography using hexane over silica 1.01 mmol), potassium tert-butoxide (458 mg, 4.02 mmol),
1
gel. Yield 92 mg (45%). H NMR (400 MHz, CDCl3) d 8.04 (s), and AMVN (50 mg, 0.21 mmol) were added into pyridine
7.90 (m), 7.86 (m), 7.76 (m), 7.72 (m), 7.57–7.40 (m), 7.37 (m). (3 mL) in a sealed tube. The white coloured reaction mixture
13C NMR (100 MHz, CDCl3) d 141.2, 140.8, 140.3, 138.6, 133.8, was heated at 110 1C for 8 h. After this, the reaction mixture was
133.7, 133.6, 132.6, 131.6, 130.1, 128.9, 128.4, 128.3, 128.2, poured over water (70 mL), extracted with ethyl acetate
127.65, 127.63, 127.4, 127.3, 127.2, 126.9, 126.3, 126.03, (25 mL ꢁ 3), dried over Na2SO4, and concentrated over a rotary
126.01, 125.9, 125.8, 125.6, 125.4, 124.4. HRMS (ESI) m/z evaporator. The resultant white colourless liquid which was
205.0826, calcd for C16H12 + H: 205.1012.
purified by column chromatography using hexane over silica
1-(4-Methoxyphenyl)naphthalene and 2-(4-methoxyphenyl)- gel gave two fractions: (i) first fraction, yield 0.108 g (64%)
naphthalene (22).6d 4-Iodo anisole (234 mg, 1.0 mmol), potas- 1H NMR (400 MHz, CDCl3) d 8.66 (d, J = 4.0 Hz, 1H), 7.88 (d, J =
sium tert-butoxide (448 mg, 4.0 mmol), and AMVN (52 mg, 8.0 Hz, 1H), 7.73–7.67 (m, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.18 (dt,
0.21 mmol) were added into naphthalene (128 mg, 1.0 mmol) in J = 6.0, 0.5 Hz, 2H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3)
a sealed tube. The white coloured reaction mixture was heated d 157.5, 149.6, 138.9, 136.7, 136.6, 129.5, 126.8, 121.8, 120.3,
at 110 1C. The reaction mixture was heated for 8 h. After this, 21.3. HRMS (ESI) m/z 170.0919, calcd for C12H11N + H: 170.0964.
the reaction mixture was poured over water (100 mL), extracted
3-(4-Methylphenyl)pyridine (25).5b Second fraction, yield
with ethyl acetate (25 mL ꢁ 3), dried over Na2SO4, and con- 31 mg (18%). 1H NMR (400 MHz, CDCl3) d 8.82 (d, J = 0.5 Hz, 1H),
centrated over a rotary evaporator. The resultant white colour- 8.55 (dd, J = 4.0, 0.5 Hz, 1H), 7.85 (dd, J = 8.0, 0.5 Hz, 1H), 7.47
less solid was purified by column chromatography using (d, J = 8.0 Hz, 2H), 7.34 (dd, J = 6.0, 0.5 Hz, 1H), 7.26 (d, J =
1
hexane over silica gel. Yield 95 mg (41%). H NMR (400 MHz, 8.0 Hz, 2H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3) d 148.1,
CDCl3) d 8.0 (s), 7.96–7.84 (m), 7.73 (m), 7.67 (m), 7.54–7.42 (m), 148.0, 138.0, 136.7, 134.9, 134.3, 129.8, 127.0, 123.6, 21.2.
7.05 (m), 7.30 (s), 3.88 (s). 13C NMR (100 MHz, CDCl3) d 159.3, GCMS (ESI) m/z 169.1, calcd for C12H11N: 169.1.
159.0, 139.9, 138.2, 133.9, 133.8, 133.7, 133.1, 132.3, 131.8,
2-(4-Methoxyphenyl)pyridine (26).5b 4-Iodo anisole (237 mg,
131.1, 128.4, 128.34, 128.26, 128.1, 127.6, 127.3, 126.9, 126.2, 1.01 mmol), potassium tert-butoxide (450 mg, 4.01 mmol), and
126.1, 125.9, 125.7, 125.4, 125.0, 114.3, 113.7, 29.7, 29.4. AMVN (50 mg, 0.21 mmol) were added into pyridine (3 mL) in a
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sealed tube. The white coloured reaction mixture was heated at monitored by TLC. The reaction mixture was heated for 8 h.
110 1C for 8 h. After this, the reaction mixture was poured over After this, the reaction mixture was poured over water (70 mL),
water (70 mL), extracted with ethyl acetate (25 mL ꢁ 3), dried extracted with ethyl acetate (25 mL ꢁ 3), dried over Na2SO4, and
over Na2SO4, and concentrated over a rotary evaporator, which concentrated on a rotary evaporator. The white colourless liquid
resulted in white colourless liquid. Purification by column was purified by column chromatography using hexane–EtOAc
chromatography using hexane over silica gel gave three frac- (8 : 2) over silica gel. Yield 0.102 g (55%). 1H NMR (400 MHz,
1
tions: (i) first fraction, yield 93 mg (50%) H NMR (400 MHz, CDCl3) d 8.51 (d, J = 7.0 Hz, 1H), 7.94 (d, J = 8.0 Hz, 2H), 7.45 (t, J =
CDCl3) d 8.63 (d, J = 4.0 Hz, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.66 (dt, 8.0 Hz, 2H), 7.39 (t, J = 8.0 Hz, 1H), 7.22 (dd, J = 4.0 Hz, 1H), 6.76
J = 7.0, 1.0 Hz, 1H), 7.64 (d, J = 4.0 Hz, 1H), 7.16–7.13 (m, 2H), (dd, J = 8.0, 2.0 Hz, 1H), 3.89 (s, 3H). 13C NMR (100 MHz, CDCl3)
7.23–7.19 (t, J = 8.0 Hz, 1H), 3.84 (s, 3H). 13C NMR (100 MHz, d 166.4, 159.3, 150.9, 139.5, 129.0, 128.7, 127.0, 108.1, 106.9, 55.2.
CDCl3) d 160.5, 157.1, 149.5, 136.7, 132.0, 128.2, 121.4, 119.8, HRMS (ESI) m/z 186.0905, calcd for C12H11NO + H: 186.0913.
114.1, 55.4. HRMS (ESI) m/z 186.0937, calcd for C12H11NO + H:
4-Methoxy-2-(4-methoxyphenyl)pyridine (32). 4-Iodo anisole
(232 mg, 0.99 mmol), potassium tert-butoxide (450 mg, 4.0 mmol)
186.0913.
3-(4-Methoxyphenyl)pyridine (27).5b Second fraction, yield and AMVN (52 mg, 0.21 mmol) were added into 4-methoxy
1
30 mg (16%). H NMR (400 MHz, CDCl3) d 8.80 (d, J = 2.0 Hz, pyridine (2.5 mL) in a sealed tube. The white coloured reaction
1H), 8.52 (dd, J = 4.0, 0.5 Hz, 1H), 7.85 (dt, J = 8.0, 0.5 Hz, 1H), mixture was heated at 110 1C. The progress of the reaction was
7.50 (d, J = 8.0 Hz, 2H), 7.32 (q, J = 6.0 Hz, 1H), 6.99 (d, J = monitored by TLC. The reaction mixture was heated for 8 h. After
8.0 Hz, 2H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3) d 159.8, this, the reaction mixture was poured over water (70 mL).
147.7, 147.6, 134.1, 130.1, 128.2, 123.6, 114.6, 55.4. HRMS (ESI) Standard workup resulted in white colourless liquid. Purification
m/z 186.0932, calcd for C12H11N O + H: 186.0913.
by column chromatography using hexane over silica gel gave a
4-(4-Methoxyphenyl)pyridine (28).5b Third fraction, yield 20 white coloured semi-solid. Yield 0.157 g (73%). 1H NMR
mg (11%). 1H NMR (400 MHz, CDCl3) d 8.60 (d, J = 4.0 Hz, 2H), (400 MHz, CDCl3) d 8.48 (d, J = 8.0 Hz, 1H), 7.91 (d, J =
7.59 (dd, J = 8.0, 2.0 Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 2.0 Hz, 1H), 6.98 (d, J = 8.0 Hz, 2H),
8.0 Hz, 2H), 3.85 (s, 3H). 13C NMR (100 MHz, CDCl3) d 160.7, 6.74 (dd, J = 8.0, 2.0 Hz, 1H), 3.90 (s, 3H), 3.85 (s, 3H). 13C NMR
149.7, 148.3, 130.2, 128.2, 121.2, 114.6, 55.4. HRMS (ESI) m/z (100 MHz, CDCl3) d 166.7, 160.7, 158.59, 158.56, 150.3, 128.4,
186.0899, calcd for C12H11NO + H: 186.0913.
114.1, 107.7, 106.2, 55.4, 55.3. HRMS (ESI) m/z 216.0998, calcd
2-(2-Methoxyphenyl)pyridine (29).5b 2-Iodo anisole (235 mg, for C13H13NO2 + H: 216.1019.
1.0 mmol), potassium tert-butoxide (456 mg, 4.02 mmol), and
3-Methyl-2-phenylpyridine (33).18 Iodobenzene (204 mg,
AMVN (51 mg, 0.21 mmol) were added into pyridine (3 mL) in a 1.0 mmol), potassium tert-butoxide (452 mg, 4.01 mmol), and
sealed tube. The white coloured reaction mixture was heated at AMVN (48 mg, 0.19 mmol) were added into 3-methyl pyridine
110 1C. The progress of the reaction was monitored by TLC. The (3 mL) in a sealed tube. The white coloured reaction mixture
reaction mixture was heated for 8 h. After this, the reaction was heated at 110 1C. The progress of the reaction was monitored
mixture was poured over water (70 mL), extracted with ethyl by TLC. The reaction mixture was heated for 8 h. Standard workup
acetate (25 mL ꢁ 3), dried over Na2SO4, and concentrated overa and purification by column chromatography using hexane over
rotary evaporator, resulting in white colourless liquid. Purifica- silica gel gave four fractions: (i) second fraction, yield 30 mg
tion by column chromatography using hexane over silica gel (18%). 1H NMR (400 MHz, CDCl3) d 8.53 (d, J = 2.0 Hz 1H), 7.60
gave two fractions: (i) first fraction, yield 82 mg (44%). 1H NMR (d, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.44 (t, J = 6.0 Hz, 2H),
(400 MHz, CDCl3) d 8.69 (d, J = 4.0 Hz, 1H), 7.79 (d, J = 8.0 Hz, 7.39 (d, J = 6.0 Hz, 1H), 7.19 (q, J = 3.0 Hz, 1H), 2.35 (s, 3H).
1H), 7.74 (dd, J = 6.0, 1.0 Hz, 1H), 7.69 (dt, J = 8.0, 1.0 Hz, 1H), HRMS (ESI) m/z 170.1126, calcd for C12H11N + H: 170.0969.
7.36 (dt, J = 8.0, 1.0 Hz, 1H), 7.19 (dt, J = 8.0, 0.5 Hz, 1H), 7.06
3-Methyl-4-phenylpyridine (34).15 Fourth fraction, yield 14 mg
(t, J = 8.0 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 3.83 (s, 3H). 13C NMR (8%). 1H NMR (400 MHz, CDCl3) d 8.54 (s, 1H), 8.50 (t, J = 4.0 Hz,
(100 MHz, CDCl3) d 156.9, 156.1, 149.3, 131.2, 129.0, 125.6, 1H), 7.49–7.43 (m, 3H), 7.33–7.31 (m, 3H), 2.33 (s, 3H). HRMS
125.2, 121.7, 121.1, 121.0, 111.4, 55.6. HRMS (ESI) m/z 186.0977, (ESI) m/z 170.1084, calcd for C12H11N + H: 170.0969.
calcd for C12H11NO + H: 186.0913.
3-Methyl-5-phenylpyridine (35).19 Third fraction, yield 20 mg
3-(2-Methoxyphenyl)pyridine (30).5b Second fraction, yield (12%). H NMR (400 MHz, CDCl3) d 8.68 (s, 1H), 8.44 (s, 1H),
1
1
0.057 g (31%). H NMR (400 MHz, CDCl3) d 8.70 (d, J = 1.0 Hz, 7.88 (s, 1H), 7.55 (t, J = 8.0 Hz, 2H), 7.48 (t, J = 8.0 Hz, 2H), 7.44
1H), 8.48 (dd, J = 8.0, 0.5 Hz, 1H), 7.80 (t, J = 8.0 Hz, 1H), 7.32–7.23 (d, J = 8.0 Hz, 1H), 2.47 (s, 3H). HRMS (ESI) m/z 170.1159, calcd
(m, 3H), 6.98 (t, J = 8.0 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 3.75 (s, 3H). for C12H11N + H: 170.0969.
13C NMR (100 MHz, CDCl3) d 156.6, 150.0, 147.7, 134.3, 130.6,
5-Methyl-2-phenylpyridine (36).20 First fraction, yield 37 mg
129.9, 129.6, 126.9, 122.6, 121.1, 111.3, 55.5. HRMS (ESI) m/z (22%). 1H NMR (400 MHz, CDCl3) d 8.54 (s, 1H), 7.96 (d, J =
186.0927, calcd for C12H11NO + H: 186.0913.
8.0 Hz, 2H), 7.63 (q, J = 8.0 Hz, 2H), 7.46 (t, J = 8.0 Hz, 2H), 7.39
4-Methoxy-2-phenylpyridine (31).17 Iodo benzene (206 mg, (t, J = 8.0 Hz, 1H), 2.38 (s, 3H). HRMS (ESI) m/z 170.1009, calcd
1.01 mmol), potassium tert-butoxide (456 mg, 4.02 mmol) and for C12H11N + H: 170.0969.
AMVN (51 mg, 0.21 mmol) were added into 4-methoxy pyridine
2-( para-Tolyl)pyrimidine (37).21 para-Iodotoluene (218 mg,
(2 mL) in a sealed tube. The white coloured reaction mixture 1.0 mmol), potassium tert-butoxide (450 mg, 4.0 mmol), and
was heated at 110 1C. The progress of the reaction was AMVN (50 mg, 0.2 mmol) were added into pyrimidine (0.5 mL)
834 | New J. Chem., 2014, 38, 827--836
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Paper
H. Wang, F. Y. Kwong and A. Lei, J. Am. Chem. Soc., 2010,
132, 16737; (b) E. Shirakawa, K.-i. Itoh, T. Higashino and
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in a sealed tube. The white coloured reaction mixture was
heated at 110 1C for 12 h. The progress of the reaction was
monitored by TLC. After this, the reaction mixture was poured
over aqueous saturated NaHCO3 (50 mL), extracted with ethyl
acetate (25 mL ꢁ 4), dried over Na2SO4, and concentrated over a
rotary evaporator. This resulted in orange coloured liquid.
Purification by column chromatography using hexane : EtOAc
(9 : 1) over silica gel gave three fractions: (i) first fraction, yield
4 Intramolecular KOtBu mediated C–C coupling: (a) M. Rueping,
M. Leiendecker, A. Das, T. Poisson and L. Bui, Chem. Commun.,
2011, 47, 10629; (b) G. B. Bajracharya and O. Daugulis,
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Bhakuni, A. Kumar, S. J. Balkrishna, J. A. Sheikh, S. Konar
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K. Shrimali, A. Kumar and S. Kumar, Org. Synth. Coll. Vol.,
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1
18 mg (32%). H NMR (400 MHz, CDCl3) d 8.77 (d, J = 4.8 Hz,
2H), 8.31 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 7.14
(t, J = 4.8 Hz, 1H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 164.8, 157.2, 141.1, 134.8, 129.4, 128.1, 118.8, 21.5. GCMS
(ESI) m/z 169.9, calcd for C11H10N2: 170.0.
4-( para-Tolyl)pyrimidine (38) and 5-( para-tolyl)pyrimidine
(39).21,22 Second and third fractions. Yield 50 mg (44%).
4-( para-Tolyl)pyrimidine (38): 1H NMR (400 MHz, CDCl3) d
9.22 (s, 1H), 8.70 (d, J = 5.4 Hz, 1H), 7.97 (d, J = 8.2 Hz, 2H),
7.66 (d, J = 5.4 Hz, 1H), 7.29 (d, J = 8.2 Hz, 2H), 2.40 (s, 3H).
13C NMR (100 MHz, CDCl3) d 163.9, 159.0, 157.24, 141.6, 133.7,
129.8, 127.1, 116.7, 21.4. 5-( para-tolyl)pyrimidine (39): 1H NMR
(400 MHz, CDCl3) d 9.16 (s, 1H), 8.91 (s, 2H), 7.45 (d, J = 7.9 Hz,
2H), 7.24 (d, J = 4.7 Hz, 2H), 2.40 (s, 3H). 13C NMR (100 MHz,
CDCl3) d 157.2, 154.7, 139.1, 134.3, 131.3, 130.2, 126.8,
21.2. GCMS (ESI) m/z 170.0 (6.3 and 6.5 min), calcd for
5 Intermolecular KOtBu mediated C–C coupling: (a) G. P.
Yong, W. L. She, Y. M. Zhang and Y. Z. Li, Chem. Commun.,
2011, 47, 11766; (b) W.-C. Chen, Y.-C. Hsu, W.-C. n. Shih,
C.-Y. Lee, W.-H. Chuang, Y.-F. Tsai, P. P.-Y. Chen and
T.-G. Ong, Chem. Commun., 2012, 48, 6702; (c) H. Zhao,
J. Shien, J. Guo, R. Ye and H. Zeng, Chem. Commun., 2013,
49; (d) W. Liu, F. Tian, X. Wang, H. Yu and Y. Bi, Chem.
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C
11H10N2: 170.0.
4-( para-Tolyl)pyridazine (40).21 Yield (116 mg, 68%).
1H NMR (400 MHz, CDCl3) d 9.43 (s, 1H), 9.17 (d, J = 5.2 Hz,
1H), 7.62 (dd, J = 5.4 Hz, 2.5 Hz, 1H), 7.56 (d, J = 8.2 Hz, 2H),
7.32 (d, J = 7.9 Hz, 2H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 151.3, 149.8, 140.6, 138.6, 131.5, 130.3, 126.9, 123.0, 21.3.
GCMS (ESI) m/z 170.0, 7.2 min, calcd for C11H10N2: 170.
˜´˜
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Financial support from the Department of Science and Tech-
nology (DST), New Delhi, Defense and Research Development
Organization (DRDO), New Delhi, Department of Atomic Energy
(DAE), Mumbai, and IISER Bhopal is gratefully acknowledged.
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