Palladium-Catalyzed sp2 C-H Arylation of Azoarenes with Arylhydrazines

Article abstract of DOI:10.1002/cctc.201500575

Transition-metal-catalyzed direct functionalization of C-H bonds is important for new compound synthesis, but usually needs special reagents and harsh conditions. With the aid of an azo directing group, the palladium-catalyzed ortho-sp² C-H bond activation of azoarenes with hydrazines has been explored. In the reaction, the Pd catalyst reacts with azobenzene to form a palladacyclic intermediate, which reacts with a phenyl radical generated from phenylhydrazine under heating and oxygen to produce a Pd^IV or Pd^III intermediate. This finally undergoes reductive elimination to give the ortho-arylated products with the release of the Pd^II catalyst. This reaction provides a novel access to ortho-aryl azoarenes under mild conditions in high yield. Helpful hydrazines: With the aid of an azo directing group, the palladium-catalyzed ortho-sp² C-H bond activation of azoarenes with hydrazines has been explored. The catalyst reacts with azobenzene to form a palladacyclic intermediate, which reacts with a phenyl radical generated from phenylhydrazine produce a Pd^IV or Pd^III intermediate. This undergoes reductive elimination to give the ortho-arylated products and regenerate the catalyst. This reaction provides a novel access to ortho-aryl azoarenes under mild conditions in high yield.

Full text of DOI:10.1002/cctc.201500575

DOI: 10.1002/cctc.201500575
Full Papers
Palladium-Catalyzed sp2 CÀH Arylation of Azoarenes with
Arylhydrazines
Mingyang Li and Yong Ye*[a]
Transition-metal-catalyzed direct functionalization of CÀH
bonds is important for new compound synthesis, but usually
needs special reagents and harsh conditions. With the aid of
an azo directing group, the palladium-catalyzed ortho-sp2 CÀH
bond activation of azoarenes with hydrazines has been ex-
plored. In the reaction, the Pd catalyst reacts with azobenzene
a phenyl radical generated from phenylhydrazine under heat-
ing and oxygen to produce a PdIV or PdIII intermediate. This fi-
nally undergoes reductive elimination to give the ortho-arylat-
ed products with the release of the PdII catalyst. This reaction
provides a novel access to ortho-aryl azoarenes under mild
conditions in high yield.
to form
a palladacyclic intermediate, which reacts with
Introduction
In the past decade, transition-metal-catalyzed direct
functionalization of CÀH bonds has achieved great
success for the formation of CÀC and CÀheteroatom
bonds for new compound synthesis.[1] Previous re-
search indicates that transition metals such as Rh, Ru,
and Pd are effective catalysts in the direct arylation
of an aromatic ring using coupling partners that in-
clude Grignard reagents and organoboron com-
pounds.[2–6] However, the limited availability of the organobor-
on reagents or Grignard reagents and harsh conditions
hamper the general use of the protocols for practical synthesis.
Recently, research has been focused on substitutes for cou-
pling reagents, including pyridine, amide, pyrimidine, and
imine groups as anchors to form cyclopalladated intermedi-
ates,[7–10] which could further react with coupling partners such
as alcohols, carboxylic acids, and PhI(OAc)2 to realize CÀH func-
tionalization.[11–13]
Scheme 1. Pd-catalyzed ortho-arylation of arylhydrazines.
Results and Discussion
Initially, the reaction of azobenzene (1a; 0.20 mmol) with phe-
nylhydrazine (2a; 0.20 mmol) was chosen as a model reaction
to optimize the parameters. First, this transformation was car-
ried out at 808C in the presence of PdCl2 under an air atmos-
phere for 24 h to screen the various solvents (Table 1, en-
tries 1–6), and it was quickly found that CH3CN could provide
us the desired ortho-arylated product (3aa) in 52% yield
(entry 6). A further screening of Pd salts indicated that
Pd(OAc)2 was the best catalyst, which led to the formation of
3aa in 65% yield (Table 1, entries 7–10). When Pd(OAc)2 was
removed from the system, no product was formed (entry 13).
The positive results encouraged us to further change the reac-
tion temperature to achieve improved yields (entries 10–12),
and it was found that a lower reaction temperature (608C) led
to 3aa in 72% yield (entry 12). Subsequently, the substrate
scope of this transformation was examined with different sub-
stitutions at the 4-postion of the azoarene (1a–1j) and with
the use of different hydrazines (2a–2 f).
As summarized in Table 2, substitution on the benzene ring
of the azoarenes and hydrazines showed significant electronic
effects. Electron-donating groups such as 4-H, 4-Me, 4-OMe
groups resulted in excellent yields (entries 1, 2, 9, and 10). Con-
versely, electron-withdrawing groups (entries 5–8, 14, and 15)
resulted in a poor yield. Notably, the meta- and ortho-substitut-
ed azobenzene (1c and 1d) and ortho-substituted hydrazines
(2c) gave poorer yields of the respective products (3ca, 3da,
and 3ac) because of higher steric hindrance. No para-substi-
Although the above-mentioned coupling reagents are useful
for some more reactive CÀH groups, it is difficult to form
ortho-arylated products with these protocols. There are rare re-
ports about using azo groups as directing groups with arylhy-
drazine as an aryl source to achieve CÀH functionalization.[14]
Recently, it has been found that arylhydrazines can be used as
[15,16]
C
[Ph ] radicals under mild conditions.
Inspired by this, we
have designed a route to construct ortho-aryl azoarenes by Pd-
catalyzed sp2 CÀH arylation of azoarenes with arylhydrazines
by means of a radical reaction (Scheme 1). The products are
important intermediates for the synthesis of a series of new
derivatives or catalysts.[17]
[a] M. Li, Dr. Y. Ye
School of Chemistry and Chemical Engineering
South China University of Technology
Guangzhou 510641 (P.R. China)
E-mail: yeyong@scut.edu.cn
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201500575.
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tion was placed under an argon atmosphere (Scheme 3b), no
product was observed. However, when the mixture of CH3CN
(2.0 mL)/Pd(OAc)2 (10 mol%)/phenylhydrazine (2a)/air in the
absence of azobenzene was heated at 608C for 24 h, the for-
mation of benzene 2aa was observed, with 26% yield
(Scheme 3c). These controlled experiments indicate that air
possibly acts as an oxidant, and a radical process is involved in
this reaction system.
From these observations and previous reports,[18] a mecha-
nism has been proposed (Scheme 4). The reaction may be initi-
ated by arylhydrazine 2a and PdII to give diazene A. Diazene A
undergoes oxidation to give the radical intermediate B, from
which the phenyl radical C is formed with the release of mo-
lecular nitrogen. Independently, the PdII catalyst reacts with
azobenzene (1a) to form a palladacyclic intermediate D. Then,
D reacts with phenyl radical C under heating and oxygen to
produce PdIV or PdIII intermediate E.[19,20] Finally, the species E
undergoes reductive elimination to give the product 3aa with
the release of the PdII catalyst.
Table 1. Optimization of the Pd-catalyzed ortho-arylation of azobenzene
with arylhydrazines.[a]
Entry
Pd salt
Solvent
T
[8C]
Yield[b]
[%]
1
2
3
4
5
6
7
8
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdSO4
PdBr2
Pd(TFA)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
without Pd salts
PhCl
80
80
80
80
80
80
80
80
80
80
100
60
60
10
12
41
31
29
52
trace
33
57
65
PhCF3
DMSO
DMF
DCE
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
9
10
11
12
13
54
72
n.r.[c]
[a] Unless otherwise noted, the reactions were carried out by using azo-
benzene (1a; 0.20 mmol) and phenylhydrazine (2a; 0.20 mmol) with pal-
ladium catalyst (10 mol%) in solvent (2.0 mL) under an air atmosphere for
24 h in a sealed reaction tube, followed by flash chromatography on SiO2.
[b] Isolated yield. [c] n.r.=no reaction.
Conclusions
A PdII-catalyzed sp2 CÀH functionalization of azoarenes with
phenylhydrazine has been developed using atmospheric
oxygen as the oxidant under mild conditions. This protocol
provides a novel access route to the synthesis of various ortho-
aryl azoarenes with easily available materials in high yield.
tuted compound was found in the Pd/O2 system; this shows
that Pd salts cannot react with the reagents to form a seven-
membered palladacyclic intermediate in this situation.
The synthetic application of
this transformation was investi-
gated and is shown in Scheme 2.
Azobenzene 3aa could be easily
reduced to produce ortho-arylat-
ed hydrazobenzene 4, which
could be converted into 2-phe-
nylaniline 5 under TiCl4/Mg con-
Scheme 2. Synthetic application for this transformation.
ditions at 608C. The product is
an effective catalyst while bind-
ing to Pd.[17a]
To investigate the reaction
mechanism, the reaction was
performed in the presence of
2,2,6,6-tetramethylpiperidine N-
oxide (TEMPO) under the above
conditions (Scheme 3), and the
products were observed by GC-
MS and NMR spectroscopy. Con-
siderable quenching of the reac-
tion between azobenzene (1a)
and phenylhydrazine (2a) in the
presence of the radical scaveng-
er TEMPO was observed and
none of the expected product
was detected (Scheme 3a), sug-
gesting a possible radical path-
way. Additionally, when the reac- Scheme 3. Preliminary mechanistic studies.
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Experimental Section
Table 2. Pd-catalyzed ortho-arylation of azoarenes with arylhydrazines.[a]
General Information
Unless otherwise noted, the reactions were
conducted in dry solvents. Purification of the
reaction products was carried out by flash
chromatography using silica gel (40–63 mm).
Infrared spectra (IR) were recorded on
a 400 MHz spectrometer (Nicolet 380 FI-IR,
Nicolet Instrument Corporation; WI, USA) and
reported as wave length numbers (cmÀ1). Infra-
red spectra were recorded by preparing a KBr
pellet containing the title compound. 1H and
13C NMR spectra were recorded with tetrame-
thylsilane (TMS) as internal standard at ambi-
Azorenes 1
Hydrazines 2
Product 3
Yield
[%][b]
(trans/
cis)[c]
72
1
ent temperature on a 400 MHz for H NMR and
100 MHz for 13C NMR spectrometer (Bruker,
Switzerland) and the results are reported as
chemical shifts in parts per million (ppm) and
with coupling constants in Hertz (Hz). Splitting
patterns are designated as singlet (s), broad
singlet (bs), doublet (d), or triplet (t). Splitting
patterns that could not be interpreted or easily
visualized were designated as multiplets (m).
Low resolution mass spectra were recorded
using a mass spectrometer (Esquire HCT PLUS,
Bruker, Germany). Gas chromatograph mass
spectra (GC-MS) were obtained with a Agilent
6820 (USA) spectrometer.
2a
2a
2a
87 (3:1)
59
44
Preparation of azoarene substrates 1b–1j
2a
2a
2a
55
58
42
A mixture containing aniline (3 mmol), CuBr
(0.09 mmol), pyridine (0.54 mmol), and toluene
(4 mL) was stirred vigorously at 608C under air
for 24 h. After cooling down to room tempera-
ture and concentrating under vacuum, the res-
idue was purified by flash chromatography
(hexane 100%) to get the products.[21]
(E)-1,2-Di-p-tolyldiazene (1b): Yellow solid;
1H NMR (400 MHz, CDCl3): d=7.81 (d, J=
8.2 Hz, 1H), 7.30 (d, J=8.1 Hz, 1H), 2.42 ppm
(s, 2H); MS (EI, 70 eV) m/z: 210.01 (M+).
(E)-1,2-Di-m-tolyldiazene (1c): Yellow solid;
1H NMR (400 MHz, CDCl3): d=7.72 (s, 4H), 7.40
(t, J=7.9 Hz, 2H), 7.28 (d, J=7.4 Hz, 2H),
2.46 ppm (s, 6H); MS (EI, 70 eV) m/z: 210.12
(M+).
2a
48
(E)-1,2-Di-o-tolyldiazene (1d): Yellow solid;
1H NMR (400 MHz, CDCl3): d=7.61 (d, J=
7.9 Hz, 2H), 7.32 (d, J=2.8 Hz, 4H), 7.26–7.23
(m, 2H), 2.73 ppm (s, 6H); MS (EI, 70 eV) m/z:
210.09 (M+).
2a
72
(E)-1,2-Bis(4-fluorophenyl)
diazene
(1e):
Yellow solid; 1H NMR (400 MHz, CDCl3): d=
8.01–7.91 (m, 4H), 7.22 ppm (t, J=8.4 Hz, 4H);
MS (EI, 70 eV) m/z: 217.95 (M+).
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3.4 Hz, 2H), 7.49 (dd, J=10.1, 4.7 Hz, 2H), 7.45–
7.39 (m, 1H), 7.01–6.98 (m, 2H), 3.85 ppm (s,
3H); MS (EI, 70 eV) m/z: 212.10 (M+).
Table 2. (Continued)
Azorenes 1
Hydrazines 2
Product 3
Yield
[%][b]
(trans/
cis)[c]
General procedure for the synthesis of
compounds 3a–3p
The reactions were carried out by using azo-
benzene 1 (0.20 mmol) and phenylhydrazine 2
(0.20 mmol) with Pd(OAc)2 (10 mol%) in CH3CN
(2.0 mL) under an air atmosphere for 24 h in
a sealed reaction tube, followed by flash chro-
matography (hexane 100%) on SiO2.
2a
77 (10:1)
1a
1a
79
(E)-1-([1,1’-Biphenyl]-2-yl)-2-phenyldiazene
(3aa): Yellow solid; 37.2 mg, 72% yield; m.p.:
74–768C; 1H NMR (400 MHz, CDCl3): d=7.76
(dt, J=21.8, 10.1 Hz, 3H), 7.59 (d, J=7.5 Hz,
1H), 7.54 (t, J=7.3 Hz, 1H), 7.48–7.38 ppm (m,
9H); 13C NMR (100 MHz, CDCl3): d=152.8,
149.7, 141.1, 138.8, 130.9, 130.8, 129.0, 128.0,
127.6, 127.2, 123.2, 115.9 ppm; IR (KBr): n˜ =
n.r.
3587, 3458, 2779, 1892, 1532, 982, 534 cmÀ1
MS (EI, 70 eV) m/z: 258.10 (M+).
;
1a
1a
1a
85 (10:1)
54 (3:2)
40
(E)-1-(5-Methyl-[1,1’-biphenyl]-2-yl)-2-(p-tolyl)
diazene (3ba): Yellow solid; 49.8 mg, 87%
1
yield; m.p.: 71–728C; H NMR (400 MHz, CDCl3):
d=7.68 (dd, J=8.0, 5.1 Hz, 3H), 7.47 (d, J=
7.6 Hz, 2H), 7.44–7.36 (m, 4H), 7.30 (d, J=
8.0 Hz, 1H), 7.21 (d, J=12.8 Hz, 2H), 2.47 (s,
3H), 2.40 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=151.1, 147.8, 141.1, 140.9, 139.0,
131.3, 130.9, 129.6, 128.8, 127.5, 127.1, 123.1,
122.7, 115.7, 21.4, 21.4 ppm; IR (KBr): n˜ =3711,
3546, 2821, 1828, 1600, 766, 580, 540 cmÀ1; MS
(EI, 70 eV) m/z: 286.10 (M+).
[a] Unless otherwise noted, the reactions were carried out by using azobenzene 1 (0.20 mmol)
and phenylhydrazine 2 (0.20 mmol) with Pd(OAc)2 (10 mol%) in CH3CN (2.0 mL) under an air at-
mosphere for 24 h in a sealed reaction tube, followed by flash chromatography on SiO2. [b] Iso-
(E)-1-(4-Methyl-[1,1’-biphenyl]-2-yl)-2-(m-
tolyl) diazene (3ca): Yellow solid; 33.8 mg,
59% yield; m.p.: 66–698C; 1H NMR (400 MHz,
CDCl3): d=7.62–7.56 (m, 2H), 7.54 (s, 1H),
1
lated yield. [c] Determined by H NMR spectroscopy. [d] n.r.=no reaction.
(E)-1,2-Bis(4-chlorophenyl) diazene (1 f): Yellow solid; 1H NMR
(400 MHz, CDCl3): d=7.86 (d, J=8.6 Hz, 4H), 7.49 ppm (d, J=
8.6 Hz, 4H); MS (EI, 70 eV) m/z: 250.00 (M+).
7.50–7.44 (m, 3H), 7.41 (t, J=7.2 Hz, 2H), 7.39–7.32 (m, 3H), 7.24
(d, J=4.9 Hz, 1H), 2.46 (s, 3H), 2.40 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3): d=153.0, 149.6, 138.9, 138.8, 138.3, 138.0, 131.6,
130.9, 130.6, 128.8, 127.5, 127.0, 124.0, 120.2, 116.1, 21.3, 21.1 ppm;
IR (KBr): n˜ =3434, 3320, 2851, 1636, 891, 765, 697, 476 cmÀ1; MS (EI,
70 eV) m/z: 286.12 (M+).
(E)-1,2-Bis(4-bromophenyl) diazene (1g): Yellow solid; 1H NMR
(400 MHz, CDCl3): d=7.82–7.77 (m, 4H), 7.66 ppm (dd, J=6.5,
4.6 Hz, 4H); MS (EI, 70 eV) m/z: 337.85 (M+).
(E)-1-(3-Methyl-[1,1’-biphenyl]-2-yl)-2-(o-tolyl) diazene (3da):
1
Yellow oil; 25.2 mg, 44% yield; H NMR (400 MHz, CDCl3): d=7.34–
(E)-Diethyl-4,4’-(diazene-1,2-diyl) dibenzoate (1h): Yellow solid;
1H NMR (400 MHz, CDCl3): d=8.21 (d, J=8.4 Hz, 4H), 7.98 (d, J=
8.4 Hz, 4H), 4.43 (q, J=7.1 Hz, 4H), 1.43 ppm (t, J=7.1 Hz, 6H); MS
(EI, 70 eV) m/z: 326.05 (M+).
7.27 (m, 7H), 7.25–7.22 (m, 3H), 7.21–7.12 (m, 2H), 2.43 (s, 3H),
2.33 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=150.9, 140.2, 138.2,
135.9, 131.2, 130.9, 130.7, 130.3, 129.9, 129.0, 128.9, 128.1, 127.9,
127.8, 126.5, 126.2, 115.2, 19.2, 17.1 ppm; IR (KBr): n˜ =3433, 3356,
2853, 1734, 954, 766, 699, 577, 454 cmÀ1; MS (EI, 70 eV) m/z: 286.09
(M+).
(E)-1-(4-Methoxyphenyl)-2-(p-tolyl) diazene (1i): Yellow solid;
1H NMR (400 MHz, CDCl3): d=7.90 (d, J=8.9 Hz, 2H), 7.79 (d, J=
8.3 Hz, 2H), 7.29 (d, J=8.1 Hz, 2H), 7.00 (d, J=8.9 Hz, 2H), 3.88 (s,
3H), 2.42 ppm (s, 3H); MS (EI, 70 eV) m/z: 226.21 (M+).
(E)-1-(5-Fluoro-[1,1’-biphenyl]-2-yl)-2-(4-fluorophenyl)diazene
(3ea): Yellow solid; 32.4 mg, 55% yield; m.p.: 79–818C; 1H NMR
(400 MHz, CDCl3): d=7.82 (ddd, J=19.2, 8.8, 5.5 Hz, 3H), 7.47 (dd,
J=7.7, 2.4 Hz, 4H), 7.32 (ddd, J=12.7, 5.9, 3.5 Hz, 2H), 7.17 ppm
(dt, J=14.9, 5.7 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=165.5,
(E)-1-(4-Methoxyphenyl)-2-phenyldiazene (1j): Yellow solid;
1H NMR (400 MHz, CDCl3): d=7.94–7.90 (m, 2H), 7.88 (dd, J=5.2,
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7.54 (t, J=7.1 Hz, 6H), 7.15 (dd, J=
19.0, 6.0 Hz, 4H), 6.98–6.77 (m,
4H), 3.90 (s, 3H), 3.82 (s, 3H), 2.45
(s, 3H), 2.34 ppm (s, 3H); 13C NMR
(100 MHz,
CDCl3):
d=165.62,
165.45, 162.67, 162.01, 150.99,
150.70, 148.77, 147.28, 142.33,
141.93, 141.03, 138.18, 133.56,
133.47, 130.39, 130.35, 129.65,
129.54, 128.57, 127.36, 124.77,
123.81, 122.71, 118.99, 117.62,
114.08, 112.84, 108.19, 55.82, 55.51,
21.46, 21.38 ppm; IR (KBr): n˜ =
3687, 3541, 2913, 1815, 1584,
1435, 1128, 754, 579, 526 cmÀ1; MS
(EI, 70 eV) m/z: 302.09 (M+).
(E)-1-(5-Methoxy-[1,1’-biphenyl]-
2-yl)-2-phenyldiazene
(3ja):
Yellow oil; 44.4 mg, 77% yield;
1H NMR (400 MHz, CDCl3): d=8.23
(t, J=10.4 Hz, 1H), 7.92 (d, J=
Scheme 4. Proposed catalytic cycle.
8.7 Hz, 2H), 7.88 (d, J=7.5 Hz, 2H),
7.51 (dd, J=13.8, 6.9 Hz, 3H), 7.42
(d, J=7.2 Hz, 2H), 7.24–7.17 (m,
1H), 7.02 (d, J=8.7 Hz, 2H), 3.89 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=162.0, 147.0, 130.3, 129.0, 124.7, 122.5, 114.2, 55.5 ppm;
IR (KBr): n˜ =3433, 2838, 2360, 1741, 1255, 1028, 837, 806, 751,
548 cmÀ1; MS (EI, 70 eV) m/z: 288.01 (M+).
165.3, 163.0, 162.8, 149.3, 145.9, 143.7, 143.6, 137.8, 130.7, 128.7,
128.6, 127.8, 127.7, 125.2, 125.1, 118.0, 117.9, 117.3, 117.0, 116.1,
115.9, 115.3, 115.0 ppm; IR (KBr): n˜ =3673, 3446, 2649, 1081, 893,
765, 700, 578, 524 cmÀ1; MS (EI, 70 eV) m/z: 294.00 (M+).
(E)-1-(5-Chloro-[1,1’-biphenyl]-2-yl)-2-(4-chlorophenyl)diazene
(3 fa): Yellow solid; 36 mg, 58% yield; m.p.: 89–918C; 1H NMR
(400 MHz, CDCl3): d=7.85 (t, J=7.7 Hz, 1H), 7.72 (dd, J=13.7,
8.7 Hz, 2H), 7.58 (d, J=2.2 Hz, 1H), 7.51–7.39 ppm (m, 8H);
13C NMR (100 MHz, CDCl3): d=151.0, 150.8, 147.7, 142.9, 137.4,
137.1, 136.9, 130.7, 129.4, 129.3, 128.2, 127.8, 124.5, 124.2,
117.3 ppm; IR (KBr): n˜ =3694, 3472, 2921, 1383, 960, 883, 656, 572,
482 cmÀ1; MS (EI, 70 eV) m/z: 325.96 (M+).
(E)-1-(4’-Methyl-[1,1’-biphenyl]-2-yl)-2-phenyldiazene
(3ab):
1
Yellow oil; 43 mg, 79% yield; H NMR (400 MHz, CDCl3): d=7.80 (d,
J=7.4 Hz, 2H), 7.73 (d, J=8.0 Hz, 1H), 7.58 (d, J=7.6 Hz, 1H), 7.52
(dd, J=13.6, 5.9 Hz, 1H), 7.49–7.40 (m, 5H), 7.37 (d, J=7.9 Hz, 2H),
7.22 (d, J=7.4 Hz, 1H), 2.43 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=152.9, 149.8, 141.0, 137.0, 135.8, 130.8, 130.7, 129.1,
129.0, 128.8, 128.4, 128.3, 127.8, 127.5, 123.2, 120.4, 115.9,
˜
21.2 ppm; IR (KBr): n=3738, 2921, 1785, 1450, 1410, 961, 926,
513 cmÀ1; MS (EI, 70 eV) m/z: 272.06 (M+).
(E)-1-(5-Bromo-[1,1’-biphenyl]-2-yl)-2-(4-bromophenyl)diazene
(3ga): Yellow solid; 35 mg, 42% yield; m.p.: 133–1378C; 1H NMR
(400 MHz, CDCl3): d=7.71–7.66 (m, 1H), 7.58 (dd, J=20.6, 12.0 Hz,
4H), 7.53–7.49 (m, 2H), 7.37 ppm (d, J=8.8 Hz, 5H); 13C NMR
(100 MHz, CDCl3): d=151.4, 148.1, 143.1, 137.3, 133.7, 132.4, 131.1,
130.7, 127.8, 127.8, 124.7, 124.4, 117.5 ppm; IR (KBr): n˜ =3682,
2840, 1725, 1493, 1147, 749, 688, 484 cmÀ1; MS (EI, 70 eV) m/z:
413.81 (M+).
(E)-1-(4’-Methoxy-[1,1’-biphenyl]-2-yl)-2-phenyldiazene
(3ad):
1
Yellow oil; 49 mg, 85% yield; H NMR (400 MHz, CDCl3): d=7.97–
7.89 (m, 1H), 7.86–7.78 (m, 2H), 7.73 (d, J=8.0 Hz, 1H), 7.58 (dd,
J=7.6, 1.4 Hz, 1H), 7.56–7.50 (m, 2H), 7.46 (dd, J=15.3, 7.4 Hz,
4H), 7.37 (d, J=8.0 Hz, 2H), 2.43 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=152.90, 149.80, 141.03, 137.03, 135.87, 130.82, 130.78,
129.13, 129.05, 128.43, 127.80, 123.26, 115.96, 21.21 ppm; IR (KBr):
n˜ =3798, 2821, 1685, 1459, 1420, 921, 513 cmÀ1; MS (EI, 70 eV) m/z:
288.16 (M+).
(E)-Ethyl-6-((4-(ethoxycarbonyl)phenyl)diazenyl)-[1,1’-biphenyl]-
3-carboxylate (3ha): Yellow solid; 38.6 mg, 48% yield; m.p.: 118–
119 8C; 1H NMR (400 MHz, CDCl3): d=8.30 (d, J=1.6 Hz, 1H), 8.13
(dd, J=13.8, 5.2 Hz, 3H), 7.83 (d, J=8.5 Hz, 2H), 7.77 (d, J=8.4 Hz,
1H), 7.51–7.42 (m, 5H), 4.42 (dd, J=14.4, 7.1 Hz, 4H), 1.42 ppm (dt,
J=9.5, 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3): d=165.9, 155.0,
152.0, 141.3, 137.8, 132.6, 132.3, 130.8, 130.6, 129.2, 127.8, 123.1,
116.0, 61.4, 61.3, 14.3, 14.3 ppm; IR (KBr): n˜ =3125, 2989, 1735,
1634, 1468, 1246, 1106, 1056, 846, 526 cmÀ1; MS (EI, 70 eV) m/z:
402.09 (M+).
(E)-1-(4’-Chloro-[1,1’-biphenyl]-2-yl)-2-phenyldiazene
(3ae):
1
Yellow oil; 31.6 mg, 54% yield; H NMR (400 MHz, CDCl3): d=7.87
(d, J=7.1 Hz, 1H), 7.77 (t, J=7.3 Hz, 3H), 7.54 (d, J=3.7 Hz, 2H),
7.47 (dd, J=13.1, 6.1 Hz, 4H), 7.40 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3): d=152.8, 149.5, 140.0, 137.3, 133.5, 133.2, 133.2, 132.1,
131.1, 130.9, 130.6, 129.3, 129.1, 128.4, 127.8, 123.2, 122.2, 120.4,
119.9, 118.2, 116.0 ppm; IR (KBr): n˜ =3433, 2924, 2340, 1744, 1589,
1056, 749, 655, 524 cmÀ1; MS (EI, 70 eV) m/z: 292.07 (M+).
(E)-1-(5-Methoxy-[1,1’-biphenyl]-2-yl)-2-(p-tolyl) diazene (3ia)
and (E)-1-(4-methoxyphenyl)-2-(5-methyl-[1,1’-biphenyl]-2-yl)dia-
zene (3ai): Yellow solid; 43.5 mg, 72% yield; m.p.: 66–698C;
1H NMR (400 MHz, CDCl3): d=8.26 (d, J=7.6 Hz, 4H), 7.89 (d, J=
8.7 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.66 (dd, J=5.7, 3.1 Hz, 4H),
(E)-1-(4’-Fluoro-[1,1’-biphenyl]-2-yl)-2-phenyldiazene (3af): Yellow
oil; 22.1 mg, 40% yield; H NMR (400 MHz, CDCl3): d=7.92 (d, J=
7.2 Hz, 1H), 7.82–7.70 (m, 2H), 7.58–7.52 (m, 3H), 7.45 (dt, J=8.5,
5.5 Hz, 5H), 7.12 ppm (t, J=8.7 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d=163.6, 161.2, 152.8, 152.6, 149.6, 140.1, 132.4, 132.3, 131.3,
1
ChemCatChem 2015, 7, 4137 – 4142
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Full Papers
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676, 531, 493 cmÀ1; MS (EI, 70 eV) m/z: 275.96 (M+).
Synthetic application
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fied by flash chromatography (hexane/EtOAc/Et3N=40:1:1) to
afford 4.[22]
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N-Biphenyl-2-yl-N’-phenyl-hydrazine (4): Yellow solid; 1H NMR
(400 MHz, CDCl3): d=7.55–7.46 (m, 4H), 7.40 (d, J=6.9 Hz, 1H),
7.22 (dt, J=11.5, 7.2 Hz, 4H), 7.10 (d, J=8.1 Hz, 1H), 6.92 (t, J=
7.2 Hz, 1H), 6.85 (d, J=6.9 Hz, 3H), 5.88 (s, 1H), 5.54 ppm (s, 1H);
MS (EI, 70 eV) m/z: 260.13 (M+).
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(2) Low-valent titanium reagent was first prepared by stirring a mix-
ture of TiCl4 (303.5 mg 1.6 mmol) and Mg powder (97.2 mg,
4.0 mmol) in THF at room temperature under argon for 2 h. Then,
phenylhydrazine 4 (104.0 mg, 0.4 mmol) was added, and the reduc-
tion was performed at 608C for 4 h. After cooling down to room
temperature and concentrating under vacuum, the residue was pu-
rified by flash chromatography (hexane/EtOAc/Et3N=20:1:1) to
afford 5.[23]
Biphenyl-2-ylamine (5): Yellow solid; 1H NMR (400 MHz, CDCl3): d=
7.53–7.46 (m, 4H), 7.42–7.36 (m, 1H), 7.23–7.16 (m, 2H), 6.89 (dd,
J=7.4, 1.0 Hz, 1H), 6.81 (d, J=7.9 Hz, 1H), 3.79 ppm (s, 2H); MS
(EI, 70 eV) m/z: 168.89 (M+).
Acknowledgements
We thank the National Natural Science Foundation of China
(Grant No. 811736465) and Guangzhou Scientific Plan Project
(Grant No. 201510010065) for financial support.
Keywords: aromatic substitution · azo compounds · CÀH
functionalization · palladium · radical reactions
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Received: May 26, 2015
Published online on October 7, 2015
ChemCatChem 2015, 7, 4137 – 4142
www.chemcatchem.org
4142
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim