Simultaneous displacement of a nitro group during coupling of diazotized o-nitroaniline with phenols

Article abstract of DOI:10.2478/s11532-009-0150-8

During the diazo-coupling reaction, nucleophilic displacement of a nitro group was also observed. This was the main reaction (1→7) when the starting amine bore either a chlorine or methoxy group at the para position (1b-c). The newly prepared compounds (7) might serve as convenient building blocks in synthesis of some heterocycles. Versita Warsaw and Springer-Verlag Wien 2010.

Full text of DOI:10.2478/s11532-009-0150-8

Cent. Eur. J. Chem. • 8(2) • 2010 • 300–307
DOI: 10.2478/s11532-009-0150-8
Central European Journal of Chemistry
Simultaneous displacement of a nitro group during
coupling of diazotized o-nitroaniline with phenols
Research Article
Renata Farkas1, Mercedesz Törincsi1, Pal Kolonits1, Jenö Fekete2,
Oscar Jimenez Alonso3, Lajos Novak1*
1 Department of Organic Chemistry and Technology,
Budapest University of Technology and Economics,
Research Group for Alkaloid Chemistry, 1111 Budapest, Hungary
2 Department of Inorganic and Analytical Chemistry,
Budapest University of Technology and Economics, 1111 Budapest, Hungary
3 ISDIN, 08006 Barcelona, Spain
Received 14 July 2009; Accepted 7 October 2009
Abstract: During the diazo-coupling reaction, nucleophilic displacement of a nitro group was also observed. This was the main reaction (1→7)
when the starting amine bore either a chlorine or methoxy group at the para position (1b-c). The newly prepared compounds (7) might
serve as convenient building blocks in synthesis of some heterocycles.
Keywords: Azo-coupling • Nitro group • Replacement reaction • Diazene derivatives • Benzotriazoles
© Versita Sp. z o.o.
Our interest in the synthesis of heterocycles
containing benzotriazole scaffold led us to focus
1. Introduction
on the diazo-coupling reactions with functionalized
o-nitroanilines (Scheme 1).
The diazo-coupling reactions have long been used
in synthesis of various types of azobenzene
In some cases the nitro group was observed to be a
derivatives [1-4]. These coupling compounds play
leaving one [2,23-28]. In some reactions the diazonium
important roles as convenient precursors in the
group had accelerated the elimination of a nitro group
construction of heterocyclic ring systems [5-7]. Among
[29-31].
others, benzotriazole derivatives are prepared from
o-nitroanilines via formation of diazonium ion, followed
by diazo-coupling with phenol and reduction [8-11].
Some of the benzotriazols have significant
pharmacological activities [12-15]. Derivatives of
2-aryl-2H-benzotriazole have been utilized as building
vendors and no further attempts were made to purify
blocks in the preparation of ultraviolet light absorbers
2. Experimental Procedure
All solvents were used as received from commercial
or dry them. Melting points were determined on a
[11,16-19].
Büchi apparatus and are uncorrected. IR spectra were
Due to characteristic colors of azobenzenes
1
recorded on Bruker Alpha FT Spectrophotometer. H
NMR and 13C NMR spectra were recorded on a Bruker
diazo-coupling reactions are also used in visible
spectrophotometric
determination
of
bioactive
DRX-500 spectrometer operating at 500 MHz and
125 MHz, respectively. All NMR spectra are reported in
ppm relative to TMS. Merck precoated silics gel 60 F254
plates were used for TLC and Kieselgel 60 for column
compounds during preparation of pharmaceuticals and
in synthesis of dyes and pigments [20-22].
* E-mail: lnovak@mail.bme.hu
300

R. Farkas et al.
C4’-H), 7.73 (m, 1H, C5’-H), 7.74 (br. s, 1H, C3-H), 7.96
(d, J= 8.1 Hz, 1H, C6’-H), 8.07 (d, J= 8.1Hz, 1H, C3’-H),
12.22 (br. s, 1H, OH). 13C NMR (CDCl3): δ= 20.29 (CH3),
118.09 (C-6’), 118.66 (C-6), 125.23 (C-3’), 129.59 (C-4),
130.53 (C-4’), 133.48 (C5’-H), 133.84 (C-3), 136.44
(C-5), 138.03 (C-2), 143.42 (C-2’), 145.61 (C-1’), 151.15
(C-1). MS (m/z): 257 (M+, 70), 136 (M+- C6H3NO2, 75),
107 (C7H7O+, 100). Anal. Calcd for C11H18N3O3: C, 60.70;
H, 4.31; N, 16.13. Found: C, 60.48; H, 4.60; N, 15.92
NH2
N N
NO2
a
3
R
HO
Cl
NO2
X
X
2
1
R
3
1,2
X
a
b
c
Me
Ph
a
H
Cl
OMe
b
c
cyclohexyl
OH
N
O
N
N
N
+
X
R
NO2
X
4
5
R
b
+ 3
4-Methyl-2-(2-p-tolyloxyphenylazo)-phenol (7a)
Light red crystalline solid; mp 105-108°C; Rt= 13.08 min;
Rf= 0.80 (hexane-acetone, 5:2)
OH
OH
N
N
N
O
N
N
O
X
X
X
R
R
8
7
IR (KBr): 3441 (OH), 1617, 1589, 1507, 1480, 1281,
1238 cm-1. 1H NMR (CDCl3): δ= 2.33 (s, 3H, CH3), 2.37
(s, 3H, CH3), 6.88 (d, J= 8.4 Hz, 1H, C6-H), 6.97 (d, J=
8.5 Hz, 2H, C2”-H and C6”-H), 7.03 (d, J= 8.2 Hz, 1H,
C3’-H), 7.12 (m, 1H, C5-H), 7.14 (d, J= 8.5 Hz, 2H, C3”-H
and C5”-H), 7.19 (m, 1H, C5’-H), 7.39 (m, C4’-H), 7.74 (d,
J= 1.0 Hz, 1H, C3-H), 7.92 (dd, J= 8.0 and 1.4 Hz, 1H,
C6’-H), 12.9 (br. s, 1H, OH). 13C NMR (CDCl3): δ= 20.30
(CH3), 20.71 (CH3), 116.66 (C-6’), 118.08 (C-6), 118.72
(C-2” and C-6”), 119.57 (C-3’), 123.62 (C-5’), 128.91
(C-4), 130,38 (C-3” and C-5”), 132.31 (C-4’), 132.97
(C-3), 133.27 (C-4”), 134.24 C-5), 137.77 (C-2), 141.22
(C-1’), 150.69 (C-1), 154.26 (C-2’), 154.70 (C-1”). MS
(m/z): 318 (M+, 100), 213 (M+- C7H6O, 30), 196 (40).
Anal. Calcd for C20H18N2O2: C, 75.45; H, 5.70; N, 8.80.
Found: C, 75.18; H, 5.95; N, 8.59.
6
R
b
X
R
4,5,7
6,8
X R
R
a
H
Me
a
b
Cl Ph
Cl cyclohexyl
NH2
O
HO
b
c
d
e
f
H
H
Cl
Cl
Ph
cyclohexyl
Me
+
H2N
X
9
a
b
c
X
R
Ph
H
Cl
OMe Me
Me
Me
9
10
Cl cyclohexyl
OMe Me
OMe Ph
g
h
R
Scheme1. Reagents:(a)NaNO2,HCI;(b)formamidinesulfinicacid.
chromatography. Solvents were mixed on a v/v basis.
GC/MS measurements were made on a HP-5890
serial II + (GC-HP-5971A), column Restec Rtx 5-MS
30 m 0.25 mm 0.25 µm; carrier gas He, linear velocity
33.4 cm s-1 (85 kP, 200°C), split 30 mLmin-1; temperature
program 250°C for 2 min, ramp 10°C min-1, to 310°C,
15 min held; injected volume 2 µMassrange 50-450,
scan rate 1.90 scan sec-1.
x
x
3-(2-Nitrophenylazo)biphenyl-4-ol (4b)
Brown crystals; mp 132-135°C; Rf= 0.53 (hexane-
acetone, 5:2).1H NMR (CDCl3): δ= 7.15 (d, J= 8.6 Hz,
1H, C5-H), 7.36 (t, J= 7.5 Hz, 1H, C10-H), 7.47 (t, J= 7.6
Hz, 2H, C9-H z, andC11-H), 7.62 (t, J= 7.6 Hz, 1H, C4’-H),
7.64 (d, J= 7.5 Hz, 2H, C8-H and C12-H), 7.68 (dd, J=
8.6 and 2.2 Hz, 1H, C6-H), 7.75 (t, J= 7.5 Hz, 1H, C5’-H),
7.99 (d, J= 8.1 Hz, 1H, C6’-H), 8.10 (d, J= 8.1 Hz, 1H,
C3’-H), 8.21 (d, J= 2.2 Hz, 1H, C2-H), 12.35 (s, 1H, OH).
13C NMR (CDCl3): δ= 118.08 (C-6’), 119.36 (C-5), 125.33
(C-3’), 126.61 (C-8 and C-12), 127.31 (C-10), 128.96
(C-9 and C-11), 130.90 (C-4’), 131.98 (C-3), 133.55
(C-1), 133.92 (C-6), 133.94 (C-5’), 138.31 (C-3), 139.44
(C-7), 143.37 (C-1’), 145.75 (C-2’), 152.43 (C-4).
2.1. Preparation of azo-compounds 4 and 7:
General Procedure
A solution of o-nitroaniline 1 (6.9 g, 50 mmol) in conc.
HCl (25 mL) was diazotized at 0°C by the dropwise
addition of an aqueous solution of NaNO2 (5N,
10 mL,50 mmol) over the period of 30 min. The cold
solution of o-nitrobenzenediazonium chloride (2) was
then added to a cold solution of the appropriate phenol
3 (50 mmol) in a mixture of isopropanol (30 mL) and
10% solution of NaOH (45 mL) over the period of 1h.
After warming up to room temperature, the reaction
mixture was acidified with conc. HCl, and the reddish
precipitate was collected by filtration, washed with
water, and purified by column chromatography on silica
gel (hexane-toluene 1:1 as eluent).
3-[2-(Biphenyl-4-yloxy)phenylazo]biphenyl-4-ol (7b)
Brown crystals; mp 202-204°C; Rf= 0.67 (hexane-
1
acetone, 5:2). H NMR (CDCl3): δ= 7.06 (d, J= 8.6 Hz,
4-Methyl-2-(2-nitrophenylazo)phenol (4a)
1H, C5-H), 7.16 (d, J= 8.6 Hz, 2H, C3”-H and C5”-H), 7.17
(d, J= 8.6 Hz, 1H, C3’-H), 7.27 (t, J= 7.7 Hz, 1H, C5’-H),
7.33 (t, J= 7.0 Hz, 1H, C10”-H), 7.35 (t, J= 7.0 Hz, 1H,
C10-H), 7.44 (m, 2H, C9”-H and C11”-H), 7.46 (m, 3H,
C9-H, C11-H, and C4’-H), 7.56 (d, J= 7.5 Hz, 2H, C8”-H
Reddish crystals; mp 119-122°C (lit. 108-110°C [32]);
Rt= 11.00 min; Rf= 0.49 (hexane-acetone, 5:2). IR (KBr):
3441 (OH), 1621, 1599, 1579, 1495, 1450 cm-1. 1H
NMR (CDCl3): δ= 2.39 (s, 3H, CH3), 6.97 (d, J= 8.6 Hz,
1H, C6-H), 7.23 (d, J= 8.5 Hz, 1H, C5-H), 7.59 (m, 1H,
301

Simultaneous displacement of a nitro group during
coupling of diazotized o-nitroaniline with phenols
and C12”-H), 7.58 (d, J= 8.6 Hz, 3H, C6-H, C2”-H, and 144.00 (C-4”’), 151.33 (C-1), 154.67 (C-2”), 155.29
C6”-H),), 7.64 (d, J= 8.2 Hz, 2H, C8-H and C12-H), 8.00 (C-1”’). Anal. Calcd for C30H34N2O2: C, 79.26; H, 7.54; N,
(dd, J= 8.2 and 1.2 Hz, 1H, C6’-H), 8.21 (d, J= 2.1 Hz, 6.18. Found: C, 79.00; H, 7.65; N, 6.02.
1H, C2-H), 13.06 (s, 1H, OH).
13C NMR (CDCl3): δ= 116.93 (C-6’), 118.78 (C-5”), 2-(4-Chloro-2-nitrophenylazo)-4-methylphenol (4d)
118.85 (C-5), 120.32 (C-3’), 124.26 (C-5’), 126.61 (C-8 Red crystals; mp 138-141°C (Lit. [33]); Rf= 0.38 (hexane-
1
and C-12), 126.95 (C-8” and C-12”), 127.04 (C-10), toluene 1:1). H NMR (CDCl3): δ= 2.39 (s, 3H, CH3),
127.11 (C-10”), 128.64 (C-2” and C-6”), 128.79 (C-9” 6.96 (d, J= 8.5 Hz, 1H, C6-H), 7.24 (d, J= 8.5 Hz, 1H,
and C-12”), 128.88 (C-9 and C-11), 131.37 (C-2), C5-H), 7.68 (dd, J= 8.5 and 1.7 Hz, 1H, C5’-H), 7.72 (s,
131.96 (C-6), 132.70 (C-4’), 133.00 (C-1), 136.80 (C-1”), 1H, C3-H), 7.95 (d, J= 8.7 Hz, 1H, C6’-H), 8.06 (d, J= 1.7
138.09 (C-3), 139.84 (C-7), 140.44 (C-7”), 141.54 (C-1’), Hz, 1H, C3’-H), 12.13 (s, 1H, OH). 13C NMR (CDCl3): δ=
152.35 (C-4), 153.82 (C-2’), 156.70 (C-4”). Anal. Calcd 20.27 (CH3), 118.72 (C-6), 119.27 (C-6’), 125.27 (C-3’),
for C30H22N2O2: C, 81.43; H, 5.01; N, 6.33. Found: C, 129.80 (C-4), 133.51 (C-3), 133.99 (C-5’), 136.43 (C-4’),
81.17; H, 5.23; N, 6.07
136.87 (C-5), 138.09 (C-2), 141.85 (C-2’), 145.66 (C-1’),
151.22 (C-1).
4-Cyclohexyl-2-(2-nitrophenylazo)-phenyl (4c)
Light red crystals; mp 119-122°C; Rf= 0.58 (hexane- 2-(4-Chloro-2-p-tolyloxyphenylazo)-4-methylphenol
acetone, 5:2). 1H NMR (CDCl3): δ= 1.28 (m, 1H, C4”-H), (7d)
1.44 (m, 4H, C2”-H, C3”-H, C5”-H, and C6”-H), 1.77 (m, Light red crystals; mp 161-164°C; Rf= 0.66 ((hexane-
1
1H, C4”-H), 1.87 (m, 2H, C3”-H and C5”-H), 1.94 (m, 2H, toluene 1:1); Rt= 12.35 min. H NMR (CDCl3): δ= 2.35
C2”-H, C6”-H), 2.55 (m, 1H, C1”-H), 6.99 (d, J= 8.5 Hz, (s, 3H, CH3), 2.37 (s, 3H, CH3), 6.88 (d, J= 8.3, 1H,
1H, C6-H), 7.29 (dd, J= 8.5 and 2.1 Hz, 1H, C5-H), 7.59 C6-H), 6.96 (d, J= 1.8, 1H, C3’-H), 6.99 (d, J= 8.3, 2H,
(m, 1H, C4’-H), 7.73 (m, 1H, C5’-H), 7.78 (d, J= 2.0 Hz, C2”-H and C6”), 7.13 (d, J= 8.7, 2H, C5-H and C5’), 7.18
C3-H), 7.96 (dd, J= 8.1 and 0.9 Hz, 1H, C5’-H), 8.08 (dd, (d, J= 8.3, 2H, C3”-H and C5”), 7.72 (s, 1H, C3-H), 7.87 (d,
J= 8.1 and 0.9 Hz, 1H, C3’-H), 12.24 (s, 1H, OH). 13C J= 8.7, 1H, C6’-H), 12.82 (s, 1H, OH). 13C NMR (CDCl3):
NMR (CDCl3): δ= 26.09 (C-4”), 26.82 (C-3” and C-5”), δ= 20.30 (CH3), 20.77 (CH3), 117.56 (C-6’), 118.11
34.44 (C-2” and C-6”), 43.32 (C-1”), 118.11 (C-6’), (C-6), 118.89 (C-3’), 119.37 (C-2” and C-6”), 123.67
118.62 (C-6), 125.23 (C-3’), 130.46 (C-4’), 131.31 (C-3), (C-5’), 129.06 (C-4), 130.62 (C-3” and C-5”), 132.97
133.85 (C-5’), 134.56 (C-5), 138.19 (C-2), 140.11 (C-4), (C-3), 134.22 (C-4”), 134.46 (C-5), 137.81 (C-2), 139.52
143.50 (C-1’), 145.58 (C-2’), 151.39 (C-1). Anal. Calcd (C-1’), 150.62 (C-1), 153.68 (C-1”), 154.99 (C-2’). MS
for C18H19N3O3: C, 66.45; H, 5.89; N, 12.91. Found: C, (m/z): 354 (10%), 353 (5%), 352 (M+, 100%), 245 (13%),
66.60; H, 5.65; N, 12.72.
233 (15%). Anal. Calcd for C20H17ClN2O2: C, 68.09; H,
4.86; N, 7.94. Found: C, 67.82; H, 4.98; N, 7.71.
4-Cyclohexyl-2-[2-(4-cyclohexyl-phenoxy)phenylazo]
phenol (7c)
3-(4-Chloro-2-nitrophenylazo)biphenyl-4-ol (4e)
Red crystalline solid; mp 139-142°C; Rf= 0.89 (hexane- Brown crystals; mp 201-204°C; Rt= 10.35 min; Rf= 0.40
acetone, 5:2). 1H NMR (CDCl3): δ= 1.26 (m, 1H, C4””-H), (hexane-toluene, 1:1). IR (KBr): 3441 (OH), 1617, 1524,
1.28 (m, 1H, C4’-H), 1.38 (m, 4H, C2””-H, C3””-H, C5””-H, 1480, 1338, 1166 cm-1. 1H NMR (CDCl3): δ= 7.15 (d, J=
and C6””-H), 1.44 (m, 4H, C2’-H, C3’-H, C5’-H, and C6’-H), 8.7 Hz, 1H, H-5), 7.37 (t, J= 7.3 Hz, 1H, H-9), 7.47 (t, J=
1.74 (m, 1H, C4””-H), 1.77 (m, 1H, C4’-H), 1.87 (m, 6H, 7.6 Hz, 2H, H-8 and H-10), 7.63 (d, J= 7.8 Hz, 2H, H-7
C2””-H, C3””-H, C5””-H, C6””-H, C3’-H, and C5’-H), 1.94(m, and H-11), 7.71 (m, 2H, H-6 and H-5’), 8.00 (d, J= 1.8
2H, C2’-H and C6’-H), 2.48 (m, 1H, C1””-H), 2.55 (m, 1H, Hz, 1H, H-6’), 8.09 (s, 1H, H3’), 8.19 (d, J= 1.9 Hz, 1H,
C1’-H), 6.89 (d, J= 8.5 Hz, 1H, C6-H), 6.99 (d, J= 8.4 Hz, H-2), 12.25 (s, 1H, OH). 13C NMR (CDCl3): δ= 119.28
2H, C2”’-H and C6”’-H), 7.05 (d, J= 8.2 Hz, 1H, C3”-H), (C-6’), 119.42 (C-5), 125.39 (C-3’), 126.60 (C-8 and
7.17 (d, J= 8.5 Hz, 4H, C3-H, C3”-H, C3”’-H, and C5”’-H C-12), 127.38 (C-10), 128.98 (C-9 and C-11), 132.01
), 7.38 (m, 1H, C4”-H), 7.78 (d, J= 1.5 Hz, 1H, C3-H), (C-2), 133.72 (C-1), 134.09 (C-5’), 134.32 (C-6), 136.87
7.93 (dd, J= 8.0 and 1.0 Hz, 1H, C6”-H), 12.94 (s, 1H, (C-4’), 138.36 (C-3), 139.31 (C-7), 141.80 (C-1’), 145.83
OH). 13C NMR (CDCl3): δ= 26.56 (C-4’ and C-4””), 27.30 (C-2’), 152.44 (C-4). MS (m/z): 355 (15%), 354 (8%),
(C-3’, C-5’, C-3””, and C-5””), 34.98 (C-2’ and C-6’), 353 (M+, 50%), 321 (38%), 169 (100%, C12H9O+). Anal.
35.02 (C-2”” and C-6””), 43.82 (C-1’), 44.31 (C-1””), Calcd for C18H12ClN3O3: C, 61.11; H, 3.42; N, 11.88.
117.06 (C-6”), 118.43 (C-6), 119.10 (C-2”’), 120.06 Found: C, 61.38; H, 3.65; N, 11.66.
(C-3”), 123.99 (C-5”), 128.51 (C-3”’), 131.12 (C-3),
132.64 (C-5), 138.35 (C-2), 139.89 (C-4), 141.73 (C-1”),
302

R. Farkas et al.
4-(3-Chlorophenoxy)biphenyl (6a)
119.29 (C-6’), 125.28 (C-3’), 131.35 (C-3), 134.00 (C-5’),
Light yellow crystals; mp 57-60°C; Rf= 0.87 (hexane- 135.01 (C-5), 136.36 (C-4’), 138.24 (C-2), 140.29 (C-4),
toluene, 1:1). IR (KBr): 1586, 1470, 1230 cm-1. 1H NMR 141.93 (C-1’), 145.64 (C-2’), 151.46 (C-1). MS (m/z):
(CDCl3): δ= 6.94 (d, J= 8.1 Hz, 1H, H-6’), 7.04 (s, 1H, 361 (10%), 360 (7%), 359 (M+, 32%), 259 (M+- C6H11-
H-2’), 7,09 (d, J= 8.3 Hz, 3H, H-3, H-5, and H-4’), 7.26 OH, 8%), 203 (12%), 175 (C12H15O+, 100%). Anal. Calcd
(t, J= 8.1 Hz, 1H, H-5’), 7.34 (t, J= 7.3 Hz, 1H, H-10), for C18H18ClN3O3: C, 60.09; H, 5.04; N, 11.68. Found: C,
7.44 (t, J= 7.5 Hz, 2H, H-9 and H-11), 7.57 (m, 4H, H-2, 60.32; H, 5.23; N, 11.42.
H-6, H-8, and H-12). 13C NMR (CDCl3): δ= 116.80 (C-6’),
118.91 (C-2’), 119.59 (C-3), 123.33 (C-4’), 126.96 (C-8 2-[4-Chloro-2-(4-cyclohexylphenoxy)-phenylazo]-4-
and C-12), 127.20 (C-10), 128.62 (C-2 and C-6), 128.82 cyclohexylphenol (7f)
(C-9 and C-11), 130.53 (C-5’), 135.10 (C-3’), 137.10 Reddish crystals; mp 197-200°C; Rt= 6.12 min; Rf= 0.85
(C-1), 140.38 (C-7), 155.87 (C-4), 158.26 (C-1’). Anal. (hexane-toluene, 1:1). IR (KBr): 3450 (OH), 1595, 1500,
1
Calcd for C18H13ClO: C, 77.01; H, 4.67. Found: C, 76.79; 1150 cm-1. H NMR (CDCl3): δ= 1.26 (m, 2H, H-4”’), 1.41
H, 4.88.
(m, 4H, H-3”’ and H-5”’), 1.44 (m, 4H, H-2”’ and H-6”’),
1.76 (br. s, 2H, H-4”’), 1.86 (m, 4H, H-3”’ and H-5”’), 1.92
3-[2-(Biphenyl-4-yloxy)-4-chloro-phenylazo]biphenyl-4- (m, 4H, H-2”’ and H-6”’), 2.51 (m, 1H, H-1”’), 2.53 (m,
ol (7e) 1H, H-1”’), 6.90 (d, J= 8.4 Hz, 1H, H-6), 7.00 (s, 1H,
Reddish crystals; mp 218-221°C; Rf= 0.62 (hexane- H-5’), 7.02 (d, J= 8.2 Hz, 2H, H-2” and H6”), 7.14 (d,
toluene, 1:1). IR (KBr): 3440 (OH), 1612, 1584, 1512, J= 8.6 Hz, 1H, H-3’), 7.19 (d, J= 8.4 Hz, 1H, H-5), 7.21
1
1482, 1240 cm-1. H NMR (CDCl3): δ= 7.06 (d, J= 8.7 (d, J= 8.2 Hz, 2H, H-3” and 5”), 7.76 (s, 1H, H-3), 7.87
Hz, 1H, C5-H), 7.11 (br. s, 1H, C3’-H), 7.19 (d, J= 8.4 Hz, (d, J= 8.6 Hz, 1H, H-2’), 12.83 (s, 1H, OH). 13C NMR
2H, C3”-H and C5”-H), 7.22 (dd, J= 8.9 and 1.3 Hz, 1H, (CDCl3): δ= 26.13 (C-4”’), 26.88 (C-3”’ and C-5”’), 34.54
C5’-H), 7.35 (t, J= 7.2 Hz, 2H, C10-H and C10”-H), 7.44 and 34.57 (C- 2”’ and C-6”’), 43.38 and 43.93 (C-1”’),
(t, J= 7.2 Hz, 2H, C9”-H and C11”-H), 7.46 (t, J= 7.2 Hz, 117.55 (C-2’), 118.05 (C-6), 119.00 (C-5’), 119.26 (C-2”
2H, C9-H and C11-H), 7.58 (d, J= 7.5 Hz, 2H, C8”-H and and C-6”), 123.67 (C-3’), 128.34 (C-3” and C-5”), 130.71
C12”-H), 7.60 (dd, J= 9.0 and 1.0 Hz, 1H, C6-H), 7.62 (d, (C-3), 132.52 (C-5), 137.70 (C-4’), 137.95 (C-2), 139.62
J= 9.0 Hz, 2H, C2”-H and C6”-H), 7.64 (d, J= 8.2 Hz, 2H, (C-1’), 144.46 (C-4”), 150.87 (C-1), 153.86 (C-1”),
C8-H and C12-H), 7.95 (d, J= 8.7 Hz, 1H, C6’-H), 8.20 154.90 (C-6’). MS (m/z): 488 (M+, <1), 303 (35), 302
(d, J= 1.0 Hz, 1H, C2-H), 12.95 (s, 1H, OH). 13C NMR (28), 301 [M++1 – C12H14NO, (100%)], 258 (8), 142 (30).
(CDCl3): δ= 117.85 (C-6’), 118.89 (C-5), 119.44 (C-3” Anal. Calcd for C30H33ClN2O2: C, 73.68; H, 6.80; N, 5.73.
and C-5”), 119.69 (C-3’), 124.35 (C-5’), 126.61 (C-8 and Found: C, 73.39; H, 6.56; N, 5.49.
C-12), 127.02 (C-8” and C-12”), 127.11 (C-10), 127.30
(C-10”), 128.84 (C-2” and C-6”), 128,87 (C-9” and 1-(3-chlorophenoxy)-4-cyclohexylbenzene (6b)
C-11”), 128.90 (C-9 and C-11), 131.37 (C-2), 132.23 Red oil. [34] Rf= 0.94 (hexane-toluene, 1:1). H NMR
1
(C-6), 133.16 (C-1), 137.67 (C-1”), 138.12 (C-3), 138.23 (CDCl3): δ= 1.26 (m, 1H, C4”-H), 1.39 (m, 4H, C2”-H,
(C-4’), 139.76 (C-7), 139.81 (C-1’), 140.26 (C-7”), C3”-H, C5”-H, and C6”-H), 1.75 (m, 1H, C4”-H), 1.84 (m,
152.29 (C-4), 154.52 (C-2’), 155.67 (C-4”). Anal. Calcd 2H, C3”-H and C5”-H), 1.88 (m, 2H, C2”-H and C6”-H), 2.49
for C30H21ClN2O2: C, 75.55; H, 4.44; N, 5.87. Found: C, (m, 1H, C1”-H), 6.86 (dd, J= 8.2 and 2.3 Hz, 1H, C6’-H),
75.27; H, 4.27; N, 6.07.
6.93 (d, J= 8.5 Hz, 2H, C2-H and C6-H), 6.96 (br,s, 1H,
C2’-H), 7.02 (dd, J= 8.0 and 2.0 Hz, 1H, C4’-H), 7.18 (d,
2 - [ ( 4 - C h l o r o - 2 - n i t r o p h e n y l ) d i a z e n y l ] - 4 - J= 8.5 Hz, 2H, C3-H and C5-H), 7.21 (t, J= 8.1 Hz, 1H,
cyclohexylphenol (4f)
C5’-H). 13C NMR (CDCl3): δ= 26.12 (C-4”), 26.89 (C-3”
Red crystals; mp 188-191°C; Rt= 9.64 min; Rf= 0.47 and C-5”), 34.60 (C-2” and C-6”), 43.91 (C-1”), 116.37
(hexane-toluene, 1:1). IR (KBr): 3450 (OH), 1625, 1575, (C-6’), 118.42 (C-2’), 119.34 (C-2), 122.80 (C-4’), 128,12
1540, 1500, 1350, 1300 cm-1. 1H NMR (CDCl3): δ= 1.28 (C-3 and C-5), 130.36 (C-5’), 134.94 (C-3’), 143.96
(m, 1H, H-4”), 1.43 (m, 4H, H-2”, H-3”, H-5”, and H-6”), (C-4), 154.02 (C-1), 158.77 (C-1’).
1.77 (m, 1H, H-4”), 1.88 (m, 2H, H-3” and H-5”), 1.93
(m, 2H, H-2” and H-6”), 2.54 (m, 1H, H-1”), 6.98 (d, J= 4-Methyl-2-(4-methoxy-2-nitrophenyl-azo)phenol (4g)
8.5 Hz, 1H, H-6), 7.30 (d, J= 8.5 Hz, 1H, H-5), 7.68 (d, Red crystals; mp 159-161°C (Lit. 152°C [35]); Rt= 12.80
J= 8.7 Hz, 1H, H-5’), 7.75 (s, 1H, H-3), 7.96 (d, J= 8.7 min; Rf= 0.53 (hexane-acetone, 5:2). IR (KBr): 3442
Hz, 1H, H-6’), 8.06 (s, 1H, H-3’), 12.15 (s, 1H, OH). 13
C
(OH), 1611, 1522, 1493, 1393,1329 cm-1. 1H NMR
NMR (CDCl3): δ= 26.07 (C-4”), 26.80 (C-3” and C-5”), (CDCl3): δ= 2.38 (s, 3H, CH3), 3.95 (s, 3H, OCH3), 6.95
34.42 (C-2” and C-6”), 43.30 (C-1”), 118.68 (C-6), (d, J= 8.4 Hz, 1H, C6-H), 7.19 (dd, J= 8.4 and 1.5 Hz,
303

Simultaneous displacement of a nitro group during
coupling of diazotized o-nitroaniline with phenols
C5-H), 7.22 (dd, J= 9.1 and 2.6 Hz, 1H, C5’-H), 7.50 (d, (d, J= 2.5 Hz, 1H, C3’-H), 6.80 (dd, J= 9.1 and 2.5 Hz,
J= 2.6 Hz, 1H, C3’-H), 7.71 (br. s, 1H, C3-H), 7.98 (d, J= 1H, C5’-H), 7.03 (d, J= 8.6 Hz, 1H, C5-H), 7.17 (d, J= 8.6
9.1 Hz, C6’-H), 12.09 (br.s, OH). 13C NMR (CDCl3): δ= Hz, 2H, C3”-H and C5”-H), 7.33 (t, J= 7.3 Hz, 2H, C10-H
20.28 (CH3), 56.30 (OCH3), 109.17 (C-3’), 118.33 (C-6), and C10”-H), 7.42 (t, J= 7.5 Hz, 2H, C9”-H and C11”-H),
119.16 (C-6’), 120.28 (C-5’), 129.35 (C-4), 133.16 (C-3), 7.44 (t, J= 7.5Hz, 2H, C9-H and C11-H), 7.53 (dd, J= 8.5
135.40 (C-5), 137.25 (C-1’), 137.84 (C-2), 146.97 (C-2’), and 2.1 Hz, 1H, C6-H), 7.56 (d, J= 8.8 Hz, 2H, C8”-H
150.30 (C-1), 161.40 (C-4’). MS (m/z): 287 (M+, 100), and C12”-H), 7.58 (d, J= 8.8 Hz, 2H, C2”-H and C6”-H),
241 (M+- NO2 , 12), 180 (M+- C7H7O, 15).
7.63 (d, J= 7.5 Hz, 2H, C8-H and C12-H), 8.00 (d, J= 9.1
Hz, 1H, C6’-H), 8.15 (d, J= 2.1 Hz, 1H, C2-H), 13.05 (s,
4-Methyl-2-(4-methoxy-2-p-tolyloxy-phenylazo)phenol 1H, OH). 13C NMR (CDCl3): δ= 55.81 (OCH3), 104.87
(7g) (C-3’), 110.65 (C-5’), 118.02 (C-6’), 118.63 (C-5), 118.93
Reddish crystals; mp 123-125°C; Rt= 14.02 min; Rf= (C-5”), 126.59 (C-8 and C-12), 126.94 (C-8” and C-12”),
0.63 (hexane-acetone, 5:2). IR (KBr): 3440 (OH), 1649, 127.14 (C-10”), 128.65 (C-6”), 128.79 (C-9” and C-11”),
1595, 1584, 1498, 1290 cm-1. 1H NMR (CDCl3): δ= 2.33 128.83 (C-9 and C-11), 130.73 (C-2), 130.99 (C-6),
(s, 3H, CH3), 2.36 (s, 3H, CH3), 3.78 (s, 3H, OCH3), 6.50 132.81 (C-1), 135.71 (C-1’), 136.94 (C-1”), 137.95
(d, J= 2.4 Hz, 1H, C3’-H), 6.73 (dd, J= 9.0 and 2.4 Hz, (C-3), 140.01 (C-7), 140.38 (C-7”), 152.14 (C-4), 155.45
1H, C5’-H), 6.87 (d, J= 8.4 Hz, 1H, C6-H), 6.99 (d, J= 8.4 (C-2’), 156.36 (C-4”), 163.64 (C-4’). Anal. Calcd for
Hz, 2H, C2”-H and C6”-H), 7.08 (dd, J= 8.5 and 1.5 Hz, C31H24N2O3: C, 78.79; H, 5.12; N, 5.93. Found: C, 78.60;
1H, C5-H), 7.15 (d, J= 8.4 Hz, 2H, C3”-H and C5”-H), 7.69 H, 5.25; N, 6.12.
(s, 1H, C3-H), 7.94 (d, J= 9.0 Hz, 1H, C6’-H), 12.80 (br.
s, OH). 13C NMR (CDCl3): δ= 20.33 (CH3), 20.74 (CH3), Preparation of 3-(5-Chlorobenzo-triazol-2-yl)biphenyl-4-
55.74 (OCH3), 104.19 (C-3’), 110.02 (C-5’), 117.87 ol (8a)
(C-6’), 117.92 (C-6), 118.91 (C-2” and C-6”), 128.79 (C- Formamidinesulfinic acid (3.6 g, 33.5 mmol) was added
4), 130.43 (C-3” and C-5”), 132.33 (C-3), 133.34 (C-5), to a stirred solution of 4e (4.8g, 15.2 mmol) in 4N NaOH
133.52 (C-4”), 135.37 (C-1’), 137.57 (C-2), 150.46 (30 mL, 120 mmol) and the resulting mixture was heated
(C-1), 154.32 (C-1”), 155.95 (C-2’), 163.46 (C-4’). MS under reflux for 30 min.After cooling to room temperature
(m/z): 348 (M+, 100), 242 (M+- C7H6O, 35),198 (62). the precipitate was collected by filtration, washed with
Anal. Calcd for C21H20N2O3: C, 72.40; H, 5.79; N, 8.04. cold water and dried. Yield: 4.0 g (82%), yellow crystals;
1
Found: C, 72.17; H, 5.60; N, 7.80.
mp 136-139°C; Rf= 0.85 (hexane – acetone 5:2). H
NMR (CDCl3): δ= 7.26 (d, J= 8.1 Hz, 1H, C5-H), 7.36
(t, J= 7.5 Hz, 1H, C10-H), 7.43 (dd, J= 9.0 and 1.0 Hz,
3-(4-Methoxy-2-nitrophenylazo) biphenyl-4-ol (4h)
Red crystals; mp 148-151°C; Rf= 0.54 (hexane-EtOAc, 1H, C6’-H), 7.46 (t, J= 8.0 Hz, 2H, C9-H and C11-H), 7.60
4:1). IR (KBr): 3440 (OH), 1613, 1571, 1522, 1479, (dd, J= 8.5 and 2.0 Hz, 1H, C6-H), 7.65 (d, J= 7.6 Hz,
1444 1330, 1262 cm-1. 1H NMR (CDCl3): δ= 3.94 (s, 3H, 2H, C8-H and C12-H), 7.88 (d, J= 9.1 Hz, 1H, C7’-H), 7.93
OCH3), 7.11 (d, J= 8.6 Hz, 1H, C5-H), 7.22 (dd, J= 9.0 (d, J= 1.0 Hz, 1H, C4’-H), 8.61 (d, J= 2.0 Hz, 1H, C2-H),
and 2.5 Hz, 1H, C5’-H), 7.34 (t, J= 7.2 Hz, 1H, C10-H), 11.10 (s, 1H, OH). 13C NMR (CDCl3): δ= 116.73 (C-4’),
7.45 (t, J= 7.5 Hz, 2H, C9-H and C11-H), 7.51 (d, J= 2.8 118.87 (C-7’), 119.50 (C-5), 119.54 (C-2), 125.24 (C-3),
Hz, 1H, C3-H), 7.62 (d, J= 8.0 Hz, 3H, C6-H, C7-H, and 126.78 (C-8 and C-12), 127.33 (C-10), 128.90 (C-9 and
C12-H), 8.00 (d, J= 9.2 Hz, 1H, C6’-H), 8.14 (d, J= 2.2 C-11), 129.40 (C-6), 133.62 (C-1), 133.75 (C-5’), 139.59
Hz, 1H, C2-H), 12.26 (s, 1H, OH). 13C NMR (CDCl3): δ= (C-7), 141.39 (C-7a’), 143.22 (C-3a’), 149.12 (C-4).
56.30 (OCH3), 109.27 (C-3’), 119.05 (C-6’), 119.11 (C-5), Anal. Calcd for C18H12ClN3O: C, 67.19; H, 3.76. Found:
120.31 (C-5’), 126,56 (C-8 and C-12), 127.17 (C-10), C, 67.37; H, 3.98.
128.91 (C-9 and C-11), 131.54 (C-2), 132.88 (C-6),
133.28 (C-1), 137.08 (C-1’), 138.08 (C-3), 139.55 (C-7), Preparation of 2-(5-Chloro-2H-benzo[d] [1,2,3]triazol-2-
147.02 (C-2’), 151.80 (C-4), 161.63 (C-4’). Anal. Calcd yl)-4-cyclohexyl-phenol (8b)
for C19H15N3O4: C, 65.32; H, 4.33; N, 12.03. Found: C, Formamidinesulfinic acid (1.6 g, 14 mmol) and 4N
65.18; H, 4.15; N, 12.29.
NaOH (12.5 mL, 50 mmol) were added to a stirred
solution of 4f (2.3 g, 6.4 mmol) in EtOH (18 mL) and
3-[2-(Biphenyl-4-yloxy)-4-methoxy-phenylazo]biphenyl- the resulting mixture was refluxed for 30 min. After
4-ol (7h) cooling to room temperature the reaction mixture was
Brown crystals; mp 192-195°C; Rf= 0.66 (hexane- acidified with aqueous HCl, the precipitated crystals
EtOAc, 4:1). IR (KBr): 3440 (OH), 1598, 1582, 1482, were collected by filtration, washed with water, and
1288, 1255 cm-1. 1H NMR (CDCl3): δ= 3.81 (OCH3), 6.62 dried. Yield 1.1 g (53%), yellow crystals; mp 117-118°C;
304

R. Farkas et al.
Rf= 0.93 (hexane – acetone, 5:2). 1H NMR (CDCl3): δ= 2-(p-Tolyloxy)-4-chlorobenzenamine (9b)
1.28 (m, 1H, C4”-H), 1.43 (m, 2H, C3”-H and C5”-H), 1.47 Method B. Yield: 20%; brown oil [36]; Rt= 8.88 min; Rf=
(m, 2H, C2”-H and C6”-H), 1.77 (m, 1H, C4”-H), 1.87 (m, 0.58 (hexane-acetone, 5:2). IR (KBr): 3473, 3383 (NH2),
2H, C3”-H and C5”-H), 1.93 (m, 2H, C2”-H and C6”-H), 2.57 1492, 1415, 1380 cm-1. 1H NMR (CDCl3): δ= 2.32 (s, 3H,
(m, 1H, C1”-H), 7.11 (d, J= 8.4 Hz, C6-H), 7.21 (d, J= 8.0 CH3), 3.91 (br.s, 2H,NH2), 6.71 (d, J= 8.4 Hz, 1H, C6-H),
Hz, C5-H), 7.42 (d, J= 9.0 Hz, C6’-H), 7.87 (d, J= 9.0 Hz, 6.76 (d, J= 2.0 Hz, 1H, C3-H), 6.88 (d, J= 8.4 Hz, 3H,
C7’-H), 7.93 (s, 1H, C4’-H), 8.20 (s, 1H, C3’-H), 10.88 (br. C5-H, C2’-H and C6’-H), 7.12 (d, J= 8.3 Hz, 2H, C3’-H and
s, 1H, OH). 13C NMR (CDCl3): δ= 26.07 (C-4”), 26.85 C5’-H). 13C NMR (CDCl3): δ= 20.65 (CH3), 116.89 (C-6),
(C-3” and C-5”), 34.56 (C-2” and C-6”), 43.71 (C-1”), 118.04 (C-2’ and C-6’), 118.85 (C-3), 122.92 (C-4),
116.69 (C-4’), 118.83 (C-7’), 118.87 (C-6), 119.04 (C-3), 123.90 (C-5), 130.36 (C-3’ and C-5’), 133.13 (C-4’),
124.76 (C-2), 129.19 (C-6’), 129.52 (C-5), 133.53 (C-5), 136.46 (C-1), 144.77 (C-2), 154.19 (C-1’). MS (m/z):
140.36 (C-4), 141.34 (C-7a’), 143.17 (C-3a’), 147.72 233 (M+, 100), 218 (M+- CH3, 15), 196 (M+- Cl, 8), 154
(C-1). Anal. Calcd for C18H18ClN3O: C, 65.95; H, 5.53. (M+- C7H7, 12).
Found: C, 65.67; H, 5.72.
2(p-Tolyloxy)-4-methoxybenzenamine (9c)
2-(p-Tolyloxy)-4-methoxybenzenamine (9c). Reduction Method B. Yield: 22%; brown oil; Rf= 0.62 (hexane-
1
of compounds 7
acetone, 5:2). H NMR (CDCl3): δ= 2.30 (s, 3H, CH3),
Method A: Formamidinesulfinic acid (0.44 g, 4 mmol) 3.66 (s, 3H, OCH3), 3.72 (br. s, 2H, NH2), 6.44 (d, J=
was added to a suspension of compound 7 (1.8 mmol) 2.5 Hz, 1H, C3-H), 6.54 (dd, J= 8.6 and 2.5 Hz, 1H,
in aqueous NaOH solution (1.4 mL, 40%, 20 mmol) and C5-H), 6.74 (d, J= 8.6 Hz, 1H, C6-H), 6.87 (d, J= 8.3 Hz,
the resulting mixture was heated under reflux for 30 min. 2H, C2’-H and C6’-H), 7.09 (d, J= 8.3 Hz, 2H, C3’-H and
After cooling the reaction mixture, the precipitate was C5’-H). 13C NMR (CDCl3): δ= 20.61 (CH3), 55.74 (OCH3),
collected by filtration, washed with water, and purified by 106.10 (C-3), 109.71 (C-5), 117.21 (C-6), 117.48 (C-2’
column chromatography (hexane-acetone, 5:2).
and C-6’), 130.20 (C-3’ and C-5’), 131.70 (C-1), 132.39
Method B: Formamidinesulfinic acid (0.34 g, (C-4’), 144.57 (C-2), 153.03 (C-4), 154.81 (C-1’). Anal.
3.2 mmol) was added to a suspension of compound 7 Calcd for C14H15NO2: C, 73.34; H, 6.59; N, 6.11. Found:
(1.8 mmol) in aqueous 4N NaOH (2.8 mL, 5.6 mmol) C, 73.20; H, 6.27; N, 6.02.
and the resultant mixture was stirred on an oil bath at
50°C for 1h. After cooling, the mixture was acidified with 2-Amino-4-methylphenol (10)
2N HCl, extracted with CH2Cl2 (3 x 10 mL), the organic Yield: 23%, white crystals; mp 135-137°C (Lit. no mp was
1
extracts were dried (MgSO4), and then the solvent was added [37]); Rf= 0.38 (hexane-acetone, 5:2). HNMR
evaporated under reduced pressure. The residue was (DMSO-d6): δ= 2.08 (s, 3H, CH3), 4.38 (br. s, 2H, NH2),
purified by column chromatography (using hexane- 6.18 (d, J= 7.7 Hz, 1H, C5-H), 6.40 (br. s, 1H, C3-H), 6.50
CH2Cl2 1:1 as eluent).
(d, J= 7.7 Hz, 1H, C6-H), 8.64 (br.s, 1H, OH). 13CNMR
(DMSO-d6): δ= 20.70 (CH3), 114,43 (C-6), 115.40 (C-3),
116.90 (C-5), 127.98 (C-4), 136.42 (C-2), 141.92 (c-1).
2-(Biphenyl-4-yloxy)phenylamine (9a)
Method A. Yield: 66%, white solid; mp 92-93°C; Rf= 0.5
(hexane-acetone, 5:2). 1H NMR (CDCl3): δ= 3.82 (br. s, 3-(4-Nitrophenylazo)biphenyl-4-ol
2H, NH2), 6.74 (m-t, J= 7.5 Hz, 1H, C4-H), 6,84 (dd, J= A solution of p-nitroaniline (1.38 g, 10 mmol) in conc.
7.7 and 1 Hz, 1H, C6-H), 6.93 (dd, J= 8.1 and 1 Hz, 1H, HCl (5 mL) was diazotized at 0°C by the dropwise
C3-H), 7.00 (m-t, J= 7.5 Hz, 1H, C5-H), 7.03 (d, J= 8.7 addition of an aqueous solution of NaNO2 (5N, 5 mL,
Hz, 2H, C3’-H and C5’-H), 7.31 (t, J= 7.5 Hz, 1H, C10’-H), 12.5 mmol) over the period of 15 min. This cold solution
7.42 (t, J= 7.5 Hz, 2H, C9’-H and C11’-H), 7.52 (d, J= 8.7 of p-nitrobenzenediazonium chloride was then added
Hz, 2H, C2’-H and C6’-H), 7.54 (d, J= 7.7 Hz, 2H, C8’-H to a cold solution of the phenol 3b (1.7 g, 10 mmol)
and C12’-H). 13C NMR (CDCl3): δ= 116.55 (C-6), 117.28 in a mixture of isopropanol (15 mL) and 10% NaOH
(C-6’), 118.85 (C-4), 120.43 (C-3), 125.07 (C-5), 126.87 (9 mL) over the period of 1h. After warming up to
(C-8’ and C-12’), 126.95 (C-10’), 128.41 (C-2’ and C-6’), room temperature the reaction mixture was acidified
128.76 (C-9’ and C-11’), 135.77 (C-1’), 138.79 (C-1), with conc. HCl, and the precipitate was collected by
140.60 (C-7’), 142.98 (C-2), 157.10 (C-4’). Anal. Calcd filtration, washed with water, and purified by column
for C18H15NO: C, 82.73; H, 5.79; N, 5.36. Found: C, chromatography on silica gel (hexane-CH2Cl2 1:1, as
82.50; H, 6.00; N, 5.12.
eluent). Yield: 2.5 g (78%) yellow crystalline solid; mp
176-179°C (Lit. [38] 174-175°C); Rt= 15.03 min; Rf= 0.64
1
(hexane-acetone, 5:2). H NMR (CDCl3): δ= 7.14 (d,
305

Simultaneous displacement of a nitro group during
coupling of diazotized o-nitroaniline with phenols
Table 1. Compounds Prepared by the Coupling Reaction.
The coupling reaction of compound 2b, having an
electron withdrawing substituent at p-position, resulted
in formation of a mixture of the coupling compound
(4d-f) and the azo-ether (7d-f). Furthermore, in the
coupling reaction with 4-hydroxybiphenyl (3b) and
4-cyclohexylphenol (3c) azo-ethers 7e,f were the
major products (entries 5 and 6); small amounts of
diphenyl ethers 6a,b were also isolated in these cases.
Obviously, these ethers were formed by the reduction of
the intermediates 5e,f.
Entry Substrate and reagent
Products and Yieldsa (%)
4a 74; - ; 7a 1.6
4b 50; - ; 7b 5.4
4c 46; - ; 7c 6.6
4d 52; - ; 7d 10
4e 12; 6a 5 ; 7e 28
4f 22 ; 6b 8 ; 7f 27
4g 15 ; - ; 7g 32
4h 6.6; - ; 7h 43
1
2
3
4
5
6
7
8
1a, 3a
1a, 3b
1a, 3c
1b, 3a
1b, 3b
1b, 3c
1c, 3a
1c, 3b
Diazonium salt with methoxy group in p-position
(2c), also yielded azo-ethers 7g,h in diazo-coupling
reactions (entries 7 and 8).
a Isolated and unoptimized yields
All attempts of carrying out the coupling reactions in
acidic media have led to the slow decomposition of the
diazonium salts 2.
The structures of the new compounds were
determined by spectroscopic methods and chemical
transformations. For instance, reduction of azo
compounds 4e,f with formamidinesulfinic acid yielded
benzotriazols 8a,b (respectively). Likewise, reduction of
compounds 7a,c,g gave a mixture of two amines 9a-c
and 10.
In summary, we had investigated the diazo-coupling
reactions and observed the nitro group to be a leaving
one in aromatic nucleophilic substitution. This “side”
reaction became the main one when the starting
compound had electron withdrawing substituent at
the m-position in relationship to the nitro group. In this
position the substituents (chlorine and methoxy group)
could exert only inductive electron withdrawing effect.
Furthermore, the replacement of the nitro group should
take place on the diazonium salt (2). Our attempt to
displace the nitro group on the coupling product 4 failed
even at higher temperature.
J= 8.6 Hz, 1H, H-5), 7.37 (t, J= 7.5 Hz, 1H, H-10), 7.47 (t,
J= 7.5 Hz, 2H, H-9 and H-11), 7.63 (d, J= 7.5 Hz, 2H, H-8
and H-12), 7.69 (dd, J= 8.5 and 2.0 Hz, 1H, H-6), 8.02
(d, J= 8.8 Hz, 2H, H-2’ and H-6’), 8.21 (d, J= 2.0 Hz, 1H,
H-2), 8.39 (d, J= 8.8 Hz, 2H, H-3’ and H-5’), 12.56 (br.
s, 1H, OH). 13C NMR (CDCl3): δ= 118.98 (C-5), 122.87
(C-2’ and C-6’), 125.02 (C-3’ and C-5’), 126.59 (C-8 and
C-12), 127.40 (C-10), 128.99 (C-9 and C-11), 131.99
(C-2), 133.83 (C-3), 137.79 (C-1), 139.30 (C-7), 148.72
(C-4’), 152.38 (C-4), 153.98 (C-1’). MS (m/z): 319 (M+,
100), 197 (M+- C6H4NO2, 8), 169 (C12H8O+, 95).
3. Results and Discussion
When the coupling reaction of compound 2a was
carried out at low temperature (0-5°C) we observed
the nucleophilic displacement of the nitro group as
a side reaction (Table 1, entry 1). This prompted us
to investigate the preparation of azobenzenes from
o-nitroaniline derivatives containing various substituents
on the benzene ring (1) and on the phenol (3).
The reaction between diazonium salt 2a and phenols
3a-c provided the expected azobenzenes 4a-c in
acceptable yield. In these cases only trace amounts of
phenol ethers 7a-c were isolated (Table 1, entries 1-3).
The latter were formed in the nucleophilic displacement
of the nitro group with a phenol followed by coupling
with another phenol molecule (2→5→7).
Acknowledgments
The financial support for this investigation was provided
by ISDIN. S. A. (Barcelona, Spain) and is greatly
appreciated.
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