Azo Dyes: New Palladium- and Copper-Catalysed Coupling Reactions on an Old Template

Article abstract of DOI:10.1055/s-0036-1591571

The elaboration of azo dyes using a variety of transition-metal-catalysed reactions (Stille, Heck, Ullmann, and Suzuki couplings) is reported. This methodology has been applied to the synthesis of functionalised coumarin azo dye conjugates, substrates which may find potential application in the development of new sensors.

Full text of DOI:10.1055/s-0036-1591571

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–I
paper
A
en
O. K. Rasheed, P. Quayle
Paper
Synthesis
Azo Dyes: New Palladium- and Copper-Catalysed Coupling
Reactions on an Old Template
HO
Omer K. Rasheed*a,b
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Peter Quayle*a
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a School of Chemistry, University of Manchester, Oxford Road,
Manchester, M13 9PL, UK
peter.quayle@manchester.ac.uk
b School of Chemistry, University of Montana, Missoula, MT
59812, USA
X
R
Heck reaction
80–88%
3 examples
N
N
N
Ullmann reaction
80–83%
N
N
N
Ar
Ar
3 examples
X = Cl, Br, I
Ar = 4-MeOC6H4,
coumarin ring
omer.rasheed@mso.umt.edu
Ar
O
B
In memory of Muhammad Rashid Sheikh
O
N
N
N
N
Stille coupling
70–80%
3 examples
Suzuki coupling
80–90%
3 examples
Ar
Ar
Received: 03.02.2018
Accepted after revision: 23.03.2018
Published online: 16.05.2018
thrombocytopenia and anaemia and have also been shown
to be exert antifungal, antimicrobial, antitumour, antiviral,
and herbicidal activities.5 It is sobering to note that the azo-
link present in these compounds are largely introduced us-
ing the methodology originally reported by Griess6 in 1858,
who prepared the first aromatic diazo compound by diazo-
tisation of ortho-aminophenol with nitrous acid, a process
that was later modified by Knoevenagel.7
DOI: 10.1055/s-0036-1591571; Art ID: ss-2018-m0072-op
Abstract The elaboration of azo dyes using a variety of transition-met-
al-catalysed reactions (Stille, Heck, Ullmann, and Suzuki couplings) is
reported. This methodology has been applied to the synthesis of func-
tionalised coumarin azo dye conjugates, substrates which may find po-
tential application in the development of new sensors.
During our investigations into the development of syn-
thetic strategies for the construction of sensing agents,
which are of potential value in the diagnosis of metal-de-
pendent neurodegenerative diseases, we had an occasion to
prepare a family of new azo dyes. There is extensive litera-
ture available concerning the preparation of azo dyes,8
which are commonly prepared by new benzannulation re-
action of azo-substituted (2-allylaryl)trichloroacetates, to
afford specifically functionalised azo-napthalenes.8 In this
study, we describe the synthesis of novel coumarin azo de-
rivatives and their downstream modification using well-es-
tablished palladium-catalysed coupling reactions (Heck,
Stille, Suzuki. and Ullmann). Surprisingly these processes,
which are ubiquitous elsewhere, have found limited appli-
cation in the functionalisation of azo dyes. Here we demon-
strate that such processes can be applied to the synthesis of
functionalised azo dyes, which could find application in the
development of new medicinal agents or sensor technology.
The synthesis of the desired azo compounds was accom-
plished by standard and well-established routes,9,10 namely
from the coupling reaction between a diazonium salt and a
phenol under carefully controlled conditions of tempera-
ture and pH. Using this standard set of procedures we were
able to prepare a variety of azo dyes, which incorporate
phenolic and coumarin residues in quantitative yields. Al-
though some of these products had been reported previ-
ously in the literature,5a,8,10b,c the extent of analytical data
for many of them were scant and often incomplete. All of
Key words azo dyes, coumarin, palladium coupling, Heck reaction,
Stille reaction, Suzuki coupling, Ullmann coupling
After the discovery of mauveine,1 the first synthetic
organic dye, by Perkin, this area of chemistry has gained
much interest among researchers. Over decades various
types of dyes have been prepared and their applications in a
host of areas are well documented. The twentieth century
witnessed a massive increase in the capabilities of the
chemical industries such that almost all were replaced by
purely synthetic entities. At present, almost all type of dyes
and pigments, which are commercially available, are syn-
thetic with few exceptions of inorganic pigments. The an-
nual world-wide production of dyestuffs and pigments is
approximately 7 × 105 tonnes/year of which two thirds is
consumed by the textile industry.2,3 Azo dyes constitute the
largest group among the synthetic dyes and are produced
entirely by chemical synthesis. Azo dyes have also been in-
corporated into in a wide variety of natural and biologically
active compounds and these conjugates have extensive ap-
plications in the textile4a and paper4b industries. Azo dyes
are inextricably linked to printing processes4c and colour
photography,4d and are now to be found in photo-electronic
devices and optical storage devices.4 They have been used
as colourants in petroleum products, as polymer additives,
and historically as food additives and colourants.4 They
have also been used in medicine for the treatment of
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

B
O. K. Rasheed, P. Quayle
Paper
Synthesis
the products from these reactions were therefore fully
characterised by IR, 1H NMR, 13C NMR, and microanaly-
sis/high-resolution mass spectrometry.
OH
OH
Br
Ac
Ac
diethyl carbonate
K2CO3
NaH, 100 °C
89%
HO
O
The synthesis of coumarin-derived azo dyes has attract-
ed the attention of chemists for many years because of the
privileged status of this motif in the chemical, biochemical,
opto-electronic, and pharmaceuticals industries. The cou-
marin ring system is also present in a large range of natural
products.11 The synthesis of azo-functionalised coumarins
such as 4 and 8 involved a standard Griess/Knoevenagel
coupling sequence, as depicted in Schemes 1 and 2. Initially
we chose to investigate the diazo-coupling reaction of the
phenol 3 in which we had also incorporated an allyl group
at C-8; phenol 3 was to be prepared from the commercially
available coumarin 1. In the event, allylation of 1 was readi-
ly accomplished with allyl bromide in acetone using K2CO3
as base. The ortho-Claisen rearrangement of 2 [in N,N-di-
ethylaniline (DEA) at reflux] proceeded in a highly regiose-
lective manner and afforded 3 in good yield (67% overall
yield). With the phenol 3 in hand, its coupling reaction with
p-bromobenzenediazonium chloride was next investigated.
Gratifyingly, this coupling reaction proceeded smoothly at
0–5 °C and afforded the desired azo dye 4 in 92% yield
(Scheme 1). Overall, this process provided ready access to
the aryl bromide 4 whose palladium-catalysed cross-cou-
pling reactions are discussed later in this article.
reflux, 5 h
80%
6
5
OH
p-bromoaniline
i) NaNO2, HCl, 0 °C
ii) NaOH, H2O
O
O
O
7
Br
88%
OH
O
N
O
N
O
8
Scheme 2 Synthesis of novel coumarin azo dye 8
cellent yields8,13 and again proved to be highly regioselec-
tive. Subsequent methylation of the free phenolic residue
was then best achieved using DMSO as solvent and KOH as
base (Scheme 3).
X
X
OH
N2
SnBu3
N
N
MeI, KOH
N
N
N
+
N
Pd(OAc)2, PPh3
DMF, 100 °C
18 h
DMSO
rt
X
10
9
Br
DEA
OH
OMe
OMe
reflux, 8 h
82%
K2CO3
HO
HO
O
O
O
O
11
12
13
47–76%
O
O
O
reflux, 5 h
80 %
X = Cl (87%)
Br (87%)
I (92%)
X = Cl (90%)
Br (93%)
I (91%)
2
1
Br
Scheme 3 Synthesis of oxygenated azo dyes and subsequent Stille
cross-coupling reactions
N
N
p-bromoaniline
i) NaNO2, HCl, 0 °C
ii) NaOH, H2O
HO
O
O
At this juncture, we envisaged that C–C coupling could
be accomplished in a number of ways, the most direct of
which would be to utilise one of the plethora of palladium-
catalysed coupling reactions (e.g., Heck, Stille, Suzuki, and
Ullmann reactions) available for such purposes.14–16 The ap-
plication of palladium-catalysed reactions for the conjuga-
tion of azo dyes, however, has received only scant atten-
tion15 and we therefore wished to determine whether such
reactions were feasible in the systems we wished to devel-
op. Using 12 as a model substrate we have shown that cou-
pling with vinyl(tri-n-butyl)stannane proceeds efficiently
when using a catalyst system comprising of Pd(OAc)2/PPh3
or Pd(dppf)(OAc)2 at 100 °C in DMF. The optimised condi-
tions for these reactions are tabulated in Table 1.
92 %
3
4
Scheme 1 Synthesis of novel coumarin azo dye 4
The novel azo dye 8 was synthesised in 88% yield from 7
upon reaction with p-bromoaniline under standard diazoti-
sation conditions. The preparation of ether 7 followed a
classical coumarin synthesis starting from 2,4-dihydroxy-
acetophenone (5), which on allylation to 6, followed by
base-mediated cyclisation with diethyl carbonate12 afforded
7 in 71% yield (Scheme 2) Curiously we were unable to coax
allyl ether 8 to undergo a second ortho-Claisen rearrange-
ment under a variety of reaction conditions.
The preparation of ether-containing azo dyes was also
accomplished starting from substituted aromatic amines
via initial formation of the diazonium salt, followed by di-
azo coupling with phenol: these reactions proceeded in ex-
At this juncture, we wished to investigate the use of the
Heck reaction for the synthesis of highly conjugated styryl
azo dyes. These reactions were proved optimal when using
a catalytic system derived from Pd(OAc)2/PPh3 in the pres-
ence of Et3N and at slightly more elevated temperature (ca.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

C
O. K. Rasheed, P. Quayle
Paper
Synthesis
Table 1 Optimisation of the Reaction Conditions for Stille Cross-Coupling Reactions
X
Reagents and conditions
Yield (%) of 13
I
vinyltributylstananne (1 equiv), Pd(OAc)2 (0.1 equiv), PPh3 (0.1 equiv), DMF, 100 °C, 10 h
vinyltributylstananne (1.2 equiv), Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 100 °C, 10 h
vinyltributylstananne (1.2 equiv), Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 100 °C, 18 h
vinyltributylstananne (1.2 equiv), Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 100 °C, 18 h
vinyltributylstananne (1.2 equiv), Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 100 °C, 18 h
vinyltributylstananne (1.2 equiv), ferrocene catalysta (0.2 equiv), DMF, 24 h, 100 °C.
vinyltributylstananne (1.2 equiv), ferrocene catalysta (0.2 equiv), DMF, 24 h, 100 °C
vinyltributylstananne (1.2 equiv), ferrocene catalysta (0.2 equiv), DMF, 24 h, 100 °C
47
56
74
76
70
68
65
65
I
I
Br
Cl
I
Br
Cl
a Ferrocene catalyst: [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) acetate.
140 °C) in DMF (Scheme 4). The yields of these coupling re-
actions proved to be uniformly high (>70%) once conducted
at these higher temperatures, as tabulated in Table 2.
yields, from the cross-coupling reaction between bis(pinac-
olato)diboron (18) and 12 in the presence of Pd(dppf)Cl2 as
catalyst (Scheme 6).17a In addition, coupling of 18 with 4,
again in the presence of Pd(dppf)Cl2 as catalyst and dry
KOAc as base in 1,4-dioxane at 80 °C, afforded the desired
boronate ester 20 in 83% yield after a reaction time of 24
hours (Scheme 7).
We also report the development of an Ullmann-type
displacement reaction of halo-substituted azo dyes. Al-
though the application of the Ullmann reaction17b to the
synthesis of aromatic ethers possessing azo-functionality
has little literature precedent we were able to prepare, after
OMe
MeO
Pd(OAc)2, PPh3
N
N
N
Et3N
N
X
+
DMF, 140 °C
18 h
Y
14
Y
X = Cl, Br, I
15 Y = N; Cl (72%), Br (76%), I (74%)
16 Y = C; Br (76%), I (81%)
12
N
Scheme 4 Heck coupling reaction for the synthesis of 15 and 16
Br
4-vinylpyridine
N
N
N
Pd(OAc)2, PPh3
Et3N
N
Gratifyingly the Heck reactions between 4 and vinyl
pyridine also proceeded in acceptable yields, affording the
desired pyridyl diazo dye 17 in a yield of 83% (Scheme 5).
After these initial investigations, we extended our stud-
ies to the Suzuki-type cross-coupling reactions for the syn-
thesis of boronate esters, which are key intermediates in
Suzuki cross-coupling reactions that have such broad ap-
peal in both industry and academia. We were pleased to
note that the boronate ester 19 was obtained, in excellent
DMF, 140 °C
O
18 h
HO
O
O
HO
O
17, 81%
4
Scheme 5 Heck coupling reaction for the synthesis of 17
Table 2 Optimisation Reaction Conditions for Heck Coupling Reaction
X
Y
Reagents and conditions
Yield (%) of 17
I
N (1.0 equiv)
N (1.2 equiv)
N (1.5 equiv)
C (1.5 equiv)
C (1.5 equiv)
N (1.5 equiv)
N (1.5 equiv)
Pd(OAc)2 (0.1 equiv), PPh3 (0.1 equiv), DMF, 100 °C, 10 h
Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 100 °C, 10 h
Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 140 °C, 18 h
Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 140 °C, 18 h
Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 140 °C, 18 h
Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 140 °C, 18 h
Pd(OAc)2 (0.2 equiv), PPh3 (0.2 equiv), DMF, 140 °C, 18 h
trace
trace
74
I
I
I
81
Br
Br
Cl
82
76
72
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

D
O. K. Rasheed, P. Quayle
Paper
Synthesis
MeO
OH
OH
OMe
Pd(dppf)Cl2
dry KOAc
N
N
Br
O
O
O
N
+
B
N
21
1,4-dioxane, 80 °C
24 h
N
N
N
N
2
CuI, picolinic acid
B
O
O
18
K3PO4, 120 °C
24 h
HO
O
O
HO
O
O
X
19
X = Br (94%); I (91%)
12
Scheme 6 Suzuki coupling reaction for synthesis of 19
23, 83%
4
Scheme 9 Ullmann-type displacement reaction of halo-substituted
azo dyes leading to the synthesis of 23
O
Br
B
O
18
methods and target products were obtained in good yields.
Studies are now underway to utilise these studies to define
second generation systems, which incorporate reporter
functionalities for biomedical studies.
N
N
N
N
Pd(dppf)Cl2
dry KOAc
1-4-dioxane, 80 °C
24 h
O
HO
O
HO
O
O
20, 83%
4
All reactions were conducted in dry glassware under a N2 atmo-
sphere, unless otherwise stated. All chemicals were purchased from a
chemical supplier and used as received, unless otherwise stated. THF
was distilled from Na wire. MeCN and CH2Cl2 were distilled from
CaH2. MeOH was dried over molecular sieves (4 Å). 1H NMR spectra
were recorded at 300, 400, or 500 MHz and 13C NMR spectra at 75,
100, or 125 MHz on a Bruker AC300, AC400, or AC500 spectrometer.
Standard abbreviations were used to designate the splitting patterns
for 1H NMR spectra. Assignments were made with the aid of
DEPT135, COSY, HMBC, and HMQC experiments. Mass spectra were
recorded on one of the following spectrometers: Waters QTOF (ES,
HRMS), Thermo Finnigan MAT95XP (GC/MS, EI, HRMS), or a Hewlett
Packard 5971 MSD (GC/MS). IR spectra were recorded on a Bruker Alpha
FT-IR spectrophotometer. A Sanyo Gallenkamp melting point apparatus
was used for melting point measurements. Chromatographic purifica-
tions were performed using silica gel SDS (particle size 0.04–0.06 mm).
Scheme 7 Suzuki coupling reaction for synthesis of 20
OMe
OMe
N
N
CuI, picolinic acid
K3PO4, 120 °C
OH
24 h
N
+
N
O
HO
OH
21
X
OH
22
X = Br (73%); I (81%)
OH
12
Azo Dyes; General Procedure
Scheme 8 Ullmann-type displacement reaction of halo-substituted
To a stirred solution of the appropriate substituted aniline (1 equiv) in
aq 2 M HCl or in some cases aq 4 M HCl (13 mL/equiv) at 0 °C was
added NaNO2 solution in H2O (1 M, 10 mL) slowly so that no gas for-
mation or colouring occurred. A solution of NaOH (1–4 equiv) and
Na2CO3 (2 equiv) were added to the corresponding substituted phe-
nol, naphthol, quinoline, or coumarin (1 equiv) in H2O (20 mL/mmol
of substrate), stirred, and cooled to 0 °C. To this solution was added
the above prepared diazo compound (1 equiv) slowly at 0 °C. After 30
min, the mixture was acidified by adding aq 2 M HCl or AcOH. The
precipitate formed was collected by filtration and washed with H2O.
The crude product was purified by crystallisation.
azo dyes
some optimisation, the intermediate 22 from the SNAr reac-
tion between 12 and 21, a reaction which was catalysed using
copper(I) iodide or the commercially available chloro[1,3-
bis(2,6-diisopropylphenyl)imidazol-2-ylidenecopper(I) in the
presence of picolinic acid (Scheme 8). We have been able to
extend this initial study to the synthesis of the highly func-
tionalised azo dye 23 in excellent yield (Scheme 9), a scaf-
fold that will be amenable to post-modification via a vari-
ety of standard synthetic operations.
In summary, we have synthesised various UV-active
compounds and studied the applications of Heck, Stille, Su-
zuki, and Ullmann coupling reactions to functionalise the
readily available azo dyes. Optimisation of the reactions
conditions led to the development of general synthetic
7-(Allyloxy)-4-methyl-2H-chromen-2-one (2)18
To a mixture of 4-methylumbelliferone (1; 1.76 g, 10 mmol) and K2-
CO3 (1.65 g, 12 mmol) in acetone (10 mL/1 g of substrate) was added
allyl bromide (1.1 mL, 12 mmol) and the reaction mixture was heated
under reflux for 5 h. After cooling down to r.t., the inorganic material
was removed by filtration, and the filtrate concentrated in vacuo to afford
the title compound in essentially quantitative yield; yield: 2.2 g (98%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

E
O. K. Rasheed, P. Quayle
Paper
Synthesis
1H NMR (300 MHz, CDCl3): δ = 2.40 (3 H, s, CH3), 4.60 (2 H, d, J = 5, 2
Hz), 5.34 (1 H, dq, J = 11, 1 Hz), 5.44 (1 H, dq, J = 17, 1 Hz), 6.05 (1 H,
ddt, J = 17, 11, 5 Hz), 6.13 (1 H, s), 6.82 (1 H, d, J = 3 Hz), 6.88 (1 H, dd,
J = 9, 3 Hz), 7.50 (1 H, d, J = 9 Hz, ArH).
13C NMR (75 MHz, CDCl3): δ = 26.1, 68.8, 101.6, 107.9, 118.9, 132.1,
165.1.
MS (ES–): m/z = 191 [M]–.
HRMS: m/z calcd for C11H11O3 [M]–: 191.0713; found: 191.0711.
13C NMR (75 MHz, CDCl3): δ = 18.6 (CH3), 69.2, 101.7, 111.9, 112.7,
113.6, 118.4, 125.4, 132.1, 152.4, 155.1, 161.2, 161.5.
MS (ES+): m/z = 184 [M + H]+.
7-(Allyloxy)-4-hydroxy-2H-chromen-2-one (7)12
A solution of 4-allyloxy-2-hydroxyacetophenone (6; 3.5 g, 18.6
mmol) in diethyl carbonate (17.5 mL) was added to a suspension of
NaH (60% dispersion in mineral oil; 3.78 g, 93 mmol) in diethyl car-
bonate (18 mL) slowly at 0 °C. After addition, the reaction mixture
was heated at 100 °C for 3 h. The resulting mixture was cooled to r.t.
and then to 0 °C. The mixture was quenched by dropwise addition of
H2O until effervescence ceased. The remaining diethyl carbonate was
extracted into Et2O (3 × 35 mL). Concd HCl (12 M) was then added
dropwise to the aqueous layer until it reached pH 4. The resulting
precipitate was collected by filtration at the pump and washed with
H2O followed by PE to afford the title compound as a colourless pow-
der; yield: 3.6 g (89%); mp 220–223 °C [Lit.15 mp 235–236 °C (dec.)].
HMMS: m/z calcd for C13H12O3 [M]+: 184.0883; found: 184.0880.
8-Allyl-7-hydroxy-4-methyl-2H-chromen-2-one (3)18
7-(Allyloxy)-4-methyl-2H-chromen-2-one (2; 6.4 g, 30 mmol) and
N,N-diethylaniline (60 mL) was heated at reflux for 8 h in a Schlenk
tube and then allowed to cool to r.t. The reaction mixture was diluted
with PE and the precipitate was collected by filtration at the pump.
The precipitate was washed with ice-cold PE to afford the title com-
pound as an off-white coloured powder; yield: 5.4 g (82%).
1H NMR (300 MHz, CDCl3): δ = 7.42 (1 H, d, J = 9 Hz, ArH), 6.86 (1 H, d,
J = 9 Hz, ArH), 6.16 (1 H, br d, J = 1 Hz, ArH), 6.01 (1 H, ddt, J = 17, 10, 6
Hz), 5.87 (1 H, app s,), 5.20 (1 H, ddd, J = 17, 3, 1 Hz), 5.17 (1 H, ddd,
J = 10, 3, 1 Hz), 3.69 (2 H, dt, J = 6, 1 Hz), 2.41 (3 H, br d, J = 1 Hz, CH3).
13C NMR (75 MHz, CDCl3): δ = 160.3, 158.7, 153.8, 152.6, 135.4, 123.9,
115.0, 112.6, 112.0, 111.9, 109.9, 26.5, 18.2.
MS (ES+): m/z = 216 [M]+.
HRMS: m/z calcd for C13H13O3 [M + H]+: 217.0859; found: 217.0854.
IR (ATR): 1241, 1358, 1613, 1702, 2576, 2932 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.49 (2 H, s), 4.50 (1 H, dt, J = 5.2, 1.5
Hz), 5.23–5.29 (1 H, m), 5.35 (1 H, dq, J =17.1, 1.5 Hz, H-12), 5.96 (1 H,
ddt, J = 17.2, 10.5, 5.3, 5.3 Hz, H-11), 6.35 (1 H, d, J = 2.5 Hz, ArH-6),
6.40 (1 H, dd, J = 9.1, 2.5 Hz), 7.56 (1 H, d, J = 8.8 Hz), 12.67 (1 H, s).
13C NMR (75 MHz, CDCl3): δ = 68.9, 88.6, 101.4, 109.1, 112.5, 118.2,
124.5, 133.0, 155.4, 161.1, 166.2.
(E)-8-[Allyl-6-(bromophenyl)diazenyl]-7-hydroxy-4-methyl-2H-
chromen-2-one (4)
(E)-7-(Allyloxy)-[(4-bromophenyl)diazenyl]-4-hydroxy-2H-
chromen-2-one (8)
Prepared according to the above general procedure for azo dyes. p-
Bromoaniline (1.76 g, 10 mmol), NaNO2 (10 mL, 1 M), NaOH (0.45 g, 2
M, 80 mmol), 8-allyl-7-hydroxy-4-methyl-2H-chromen-2-one (3;
1.84 g, 10 mmol), HCl (13 mL, 2 M, 26 mmol), and Na2CO3 (5 g) afford-
ed the title compound as a dark red solid; yield: 3.74 g (92%); mp
211–212 °C.
To a stirred solution of p-bromoaniline (1.72 g, 10 mmol) in aq 2 M
HCl (13 mL, 2 M, 26 mmol) at 0 °C was added NaNO2 solution in H2O
(1 M, 10 mL) slowly so that no gas formation or colouring occurred.
NaOH (0.90 g, 4 M, 40 mmol) and Na2CO3 (2.5 g) were added to 7-(al-
lyloxy)-4-hydroxy-2H-chromen-2-one (7; 2.18 g, 10 mmol) in H2O
(40 mL/mmol of naphthol) while maintaining the temperature as
close to 0 °C as possible. The diazo compound was then added slowly
at 0 to +5 °C. After 30 min, the reaction mixture was acidified to pH 4
with aq 3 M HCl. The precipitate formed was collected by filtration,
washed with H2O, and dried in vacuo. The title compound was ob-
tained as a dark brick-red-coloured solid; yield: 3.58 g (88%); mp
165–166 °C.
IR (ATR): 1388, 1559, 1600, 1730, 3201 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.50 (3 H, d, J = 1 Hz, CH3), 3.68 (2 H, d,
J = 6 Hz), 5.05 (1 H, dd, J = 9, 1 Hz), 5.14 (1 H, dd, J = 17, 1 Hz), 5.91–
6.10 (1 H, m), 6.22 (1 H, s), 7.66–7.70 (2 H, m), 7.74–7.78 (2 H, m),
8.10 (1 H, s, CH), 13.6 (1 H, s).
13C NMR (75 MHz, CDCl3): δ = 18.8 (CH3), 26.5, 112.5, 113.7, 116.3,
115.7, 123.6, 128.2, 132.0, 134.4, 148.8, 152.3, 154.6, 160.3.
1H NMR (500 MHz, DMSO-d6): δ = 4.66 (2 H, d, J = 5.3 Hz), 5.29 (1 H,
dd, J = 10.5, 1.4 Hz), 5.43 (1 H, dd, J = 17.1, 1.7 Hz), 6.01–6.10 (1 H, m),
6.76 (1 H, d, J = 2 Hz), 6.84 (1 H, dd, J = 8.6, 2 Hz), 7.57 (4 H, d, J = 3.7
Hz), 7.86 (1 H, d, J = 8.8 Hz).
MS (ES+): m/z 399 [M + H]+.
HRMS: m/z calcd for C19H16N2BrO3 [M]+: 399.0339; found: 399.0346.
13C NMR (500 MHz, DMSO-d6): δ = 68.7, 100.8, 111.4, 116.2, 118.0,
118.9, 121.0, 127.6, 131.7, 133.2, 155.0, 158.5, 162.6.
4-Allyloxy-2-hydroxyacetophenone (6)12
To a stirred mixture of 2,4-dihydroxyacetophenone (5; 15.2 g, 100
mmol) and K2CO3 (15 g, mmol) in anhyd acetone (100 mL) was added
allyl bromide (8.6 mL, 100 mmol). The reaction mixture was heated
under reflux for 5 h and allowed to cool to r.t. The inorganic compo-
nents were separated by filtration and the solvent was concentrated
in vacuo. The product was obtained as a colourless oil; yield: 15.2 g
(80%).
MS (ES–): m/z = 399 [M]–.
HRMS: m/z calcd for C18H13BrN2O4Na [M + Na]+: 422.9931; found:
422.9935.
Anal. Calcd for C18H13N2BrO4: C, 53.8; H, 3.2; N, 6.9; Br, 20.0. Found: C,
53.3; H, 2.8; N, 6.9; Br, 20.3.
IR (ATR): 1306, 1330, 1430, 1458, 1503, 1619, 2927, 3433 cm–1
.
4-[(E)-(4-Halophenyl)diazenyl]phenols 11a–c
These compounds were prepared according to the literature.19
1H NMR (300 MHz, CDCl3): δ = 2.55 (3 H, s, CH3), 4.56 (2 H, d, J = 5.2
Hz), 5.32 (1 H, dd, J = 10.4, 1.2 Hz), 5.42 (1 H, dd, J = 17.3, 1.3 Hz),
5.96–6.10 (1 H, m), 6.40–6.48 (2 H), 7.62 (1 H, d, J = 8.8 Hz), 12.73 (1
H, br s, OH).
4-[(E)-(4-Iodophenyl)diazenyl]phenol (11a)19
Yield: 3.2 g (92%); red coloured solid; mp 164.5–166 °C (Lit.19 mp 167 °C).
IR (ATR): 783, 824, 1246, 1440, 1466, 1563, 1590, 2045, 3008 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

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O. K. Rasheed, P. Quayle
Paper
Synthesis
1H NMR (300 MHz, CDCl3) δ = 5.45 (1 H, br s, OH), 6.95 (2 H, d, J = 9
Hz), 7.62 (2 H, d, J = 8 Hz), 7.79–7.92 (4 H, m).
1H NMR (300 MHz, CDCl3): d 3.90 (3H, s), 7.02 (2H, d, J = 9 Hz), 7.63
(2H, d, J = 9 Hz), 7.77 (2H, d, J = 9 Hz), 7.92 (2H, d, J = 9 Hz).
13C NMR (75 MHz, CDCl3) δ = 96.7, 115.8, 124.2, 125.1, 138.26, 147,
13C NMR (75 MHz, CDCl3): δ = 55.5, 114.2, 124.1, 124.8, 132.2, 162.3,
152, 158.5.
151.4.
MS (ES+): m/z 325 [M + H]+, 346.9 [M + Na]+.
HRMS: m/z calcd for [C12H9IN2O + H]+: 324.9832; found: 324.982.
MS (ES+): C13H12N279BrO m/z [M + H]+ 290.9 [M + Na]+ 313.
HRMS: C13H12N279BrO requires 291.0128 found 291.0138.
Microanalysis anal. calcd for C13H12N2Br: C 53.63; H 3.81; N 9.12; Br
27.41. Found C 53.32; H 3.72; N 9.52; Br 27.30.
4-[(E)-(4-Bromophenyl)diazenyl]phenol (11b)19
Yield: 3.05 g (87%); red coloured solid; mp 168.4–170.1 °C (Lit.19 mp
155 °C).
4.2 Synthesis of (E)-1-(4-iodophenyl)-2-(4-methoxyphenyl)dia-
zene (12c)17a
IR (ATR): 1476, 1587, 1592, 2060, 3168 cm–1
.
This compound was prepared using the general procedure described
above and the following reagents: 4-[(E)-(iodophenyl)diazenyl]phe-
nol (1.34 g, 4.14 mmol), KOH (1.16 g, 20.7 mmol), methyl iodide (0.6
mL, 10 mmol). The title compound (3.1 g, 91%) was afforded as a dark
brownish red coloured solid which was further purified by recrystal-
lisation from ethanol, yield: 3.1 g (91%); mp 176.6–178 °C, (lit17a 179–
181 °C).
1H NMR (300 MHz, CDCl3): δ = 5.39 (1 H, s, OH), 6.96 (2 H, dd, J = 9, 2
Hz), 7.64 (2 H, dd, J = 9, 2 Hz), 7.76 (2 H, dd, J = 9, 2 Hz), 7.88 (2 H, dd,
J = 9, 2 Hz).
13C NMR (75 MHz, CDCl3): δ = 98.2, 115.8, 124.1, 125.1, 132.2, 146.9,
151.4, 158.6.
MS (ES+): m/z = 276 [M + H]+ [for C12H879BrN2O].
HRMS: m/z calcd for [C12H979BrN2O – H]+: 274.9816; found 274.9825;
m/z calcd for [C12H979BrN2O + H]+: 276.9796; found: 276.9805.
IR (film): 1471, 1580,1600, 2049 cm–1
1H NMR (300 MHz, CDCl3): = 3.91 (3H, s), 7.02 (2H, d, J = 9 Hz), 7.62
(2H, d, J = 8 Hz), 7.85 (2H, d, J = 8 Hz), 7.93 (2H, d, J = 9 Hz).
13C NMR (75 MHz, CDCl3): δ = 55.6, 114.2, 124.2 , 124.9, 138.2, 152.4,
162.3.
.
4-[(E)-(4-Chlorophenyl)diazenyl]phenol (11c)19
Yield: 2.98 g (87%); red coloured solid; mp 159–161 °C (Lit.19 mp 160 °C).
IR (ATR): 1474, 1575, 1587, 3179 cm–1
.
MS (ES+): m/z [M+H]+ 339; [M + Na] 361.
1H NMR (300 MHz, CDCl3): δ = 5.91 (1 H, br s, OH), 6.95 (2 H, d, J = 8
Hz), 7.47 (2 H, d, J = 8 Hz), 7.85 (4 H, dd, J = 12, 8 Hz).
13C NMR (75 MHz, CDCl3): δ = 115.8, 123.8, 125.1, 129.2, 158.86,
HRMS: C13H12N2IO 338.9989 found 338.9999.
Microanalysis anal. calcd for C13H12N2I: C 46.1; H 3.28; N 8.28. Found
C 45.96; H 3.23; N 8.20.
151.05, 146.92, 136.20.
MS (ES+): m/z = 233 [M + H]+, 255 [M + Na]+ [for C12H1035ClN2O].
MS (ES–): m/z = 231 [M – H]–.
HRMS (ES+): m/z calcd for C12H1035ClN2O [M + H]+: 233.0477; found:
Stille-Coupling Reaction; General Procedure
To a stirred mixture of the diazo compound 12 (1 mmol), Pd(OAc)2
(0.2 mmol), PPh3 (0.2 mmol) in DMF (10 mL) was added vinyltributyl-
stananne (1.2 mmol) under N2. The reaction mixture was heated at
100 °C for 24 h and then allowed to cool to r.t. The solvent was evapo-
rated in vacuo, and CH2Cl2 (15 mL) was added to the residue. The
CH2Cl2 solution was washed with brine (3 × 20 mL) and H2O (3 × 20
mL). The organic layer was dried (MgSO4) and concentrated in vacuo
to afford the crude product, which was purified by column chroma-
tography (silica gel; eluent: hexane/CH2Cl2 1:1).
233.0469.
(E)-(4-Halophenyl)-2-(4-methoxyphenyl)diazenes 12b,c; General
Procedure
General procedure for the synthesis of methyl ethers (12b)21 and
(12c)17a
To a stirred mixture of powdered potassium hydroxide (5 eq), diazo
compound (1 eq), in DMSO (10 mL) and methyl iodide (2 eq) were
added to the mixture. The reaction mixture was stirred for 5 hours at
room temperature, and then poured it into water. The organic layer
was extracted into diethyl ether or dichloromethane and then washed
with brine, dried over MgSO4, and reduced in vacuo. The crude prod-
uct was purified by flash chromatography.
(E)-1-(4-Methoxyphenyl)-2-(4-vinylphenyl)diazene (13)
Prepared according to the above general procedure from 12 (0.145 g,
0.5 mmol), Pd(OAc)2 (11 mg), PPh3 (13 mg), and tri-n-butylvinylstan-
nane (0.217 g, 0.2 mL) in DMF (10 mL); yield: 0.904 g (76%); red co-
loured solid; mp 116–118 °C.
IR (ATR): 1493, 1577, 1596, 1626, 2920, 2956 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 3.91 (3 H, s), 5.35 (1 H, dd, J = 11, 1 Hz),
5.86 (1 H, d, J = 17 Hz), 6.68–6.86 (1 H, m), 7.03 (2 H, d, J = 9 Hz), 7.55
(2 H, d, J = 8 Hz), 7.87 (2 H, d, J = 8 Hz), 7.93 (2 H, d, J = 9, 2 Hz).
Synthesis of (E)-1-(4-bromophenyl)-2-(4-methoxyphenyl)dia-
zene(12b)21
13C NMR (75 MHz, CDCl3): δ = 55.5, 114.2, 115.2, 122.8, 124.3, 126.8,
136.2, 139.5, 147.1, 152.2, 162.1.
MS (ES+): m/z = 239 [M + H]+.
HRMS: m/z calcd for C15H15N2O [M]+: 239.1179; found: 239.1182.
This compound was prepared using the general procedure described
above and the following reagents: 4-[(E)-(bromophenyl)diaze-
nyl]phenol (1.15 g, 4.14 mmol), KOH (1.16 g, 20.7 mmol), methyl io-
dide (0.6 mL,10 mmol). The title compound was afforded as a dark or-
ange red-coloured solid which was further purified by recrystallisa-
tion from ethanol, yield: 2.7 g, (93%); mp 151.2–153 °C (lit.21 146.0–
146.5 °C).
Heck Reaction; General Procedure
IR (ATR): 727, 829, 842, 1140, 1296, 1474, 1579, 1599, 2047 cm–1
.
To a stirred mixture of the diazo ether 12 (5 mmol), Pd(OAc)2 (0.2
equiv), Et3N (7 mmol), and PPh3 (0.10 mmol) in DMF was added sty-
rene or 4-vinylpyridine (7.5 mmol) under N2. The resultant mixture
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

G
O. K. Rasheed, P. Quayle
Paper
Synthesis
was heated under reflux for 18 h. After cooling to r.t., the solvent was
removed in vacuo and residue extracted with EtOAc (2 × 50 mL). The
combined organic layers were washed with brine, dried (MgSO4), and
then evaporated in vacuo. The precipitate was washed with EtOH to
remove the impurities.
ter cooling to r.t., the reaction mixture was poured into H2O and then
extracted with CH2Cl2. The combined organic layers were dried
(MgSO4) and concentrated in vacuo to afford the crude product.
(E)-1-(4-Methoxyphenyl)-2-[4-(4,4,5,5-tetramethyl-1,3,2-diox-
aborolan-2-yl)phenyl]diazene (19)
(E)-1-(4-Methoxyphenyl)-2-(pyridine-4-yl)vinyl)diazene (15)
Prepared according to the above general procedure from 12 (X = I;
1.77 g, 5.25 mmol), bis(pinacolato)diboron (2.0 g, 8.0 mmol), Pd(dp-
pf)Cl2 (0.08 g, 0.11 mmol), and dry KOAc (1.6 g, 16.0 mmol) in anhyd
1,4-dioxane (25 mL) by heating at 80 °C for 24 h. After cooling to r.t.,
the reaction mixture was poured into H2O and then extracted with
CH2Cl2. The combined organic extracts were dried (MgSO4) and con-
centrated in vacuo. The residue was taken up in CH2Cl2 (5 mL) and pu-
rified by passage through a silica gel plug to afford the title compound
as a dark red-coloured solid; yield: 1.6 g (90%); mp 154–155 °C.
Prepared according to the above general procedure from 12 (0.582 g,
2 mmol), Pd(OAc)2 (11.4 mg), PPh3 (13 mg), and 4-vinylpyridine (0.4
mL, 3 mmol) in DMF (10 mL) and Et3N (1 mL). The precipitate was
washed with EtOH to remove impurities; yield: 0.52 g (82%); red co-
loured solid; mp 224–226 °C.
IR (ATR): 1247, 1494, 1577, 1591, 3091 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 3.91 (3 H, s), 7.03 (2 H, d, J = 9 Hz), 7.11
(1 H, d, J = 16 Hz), 7.32–7.42 (3 H, m), 7.68 (2 H, d, J = 8 Hz), 7.93 (4 H,
t, J = 8 Hz), 8.61 (2 H, d, J = 6 Hz).
13C NMR (75 MHz, CDCl3): δ = 55.5, 114.2, 120.9, 123.2, 124.8, 127.2,
127.7, 132.3, 150.2, 138.0, 144.3, 147.1, 152.6, 162.2.
MS (ES+): m/z = 316 [M + H]+.
HRMS: m/z calcd for C20H18N3O [M]+: 316.1436; found: 316.1486.
IR (ATR): 2993, 1499, 1438, 1353, 1306, 1274, 1209, 1170 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.29 (12 H, s, CCH3), 3.80 (3 H, s, OCH3),
6.93 (2 H, d, J = 9.5 Hz), 7.78 (2 H, d, J = 9.0 Hz), 7.83–7.88 (4 H, m).
13C NMR (125 MHz, CDCl3): δ = 24.5, 55.2, 83.1, 83.6, 113.8, 121.4,
124.5, 135.3, 146.7, 154.1, 161.9.
MS (ES+): m/z = 339.4 [M + H]+.
HRMS: m/z calcd for C19H23BN2O3 [M]+: 338.1790; found: 338.1795.
(E)-1-(4-Methoxyphenyl)-2-[4-(E)-styrylphenyl]diazene (16)20
Prepared according to the general procedure as above from 12 (X = Br,
0.582 g, 2 mmol), Pd(OAc)2 (11.4 mg), PPh3 (13 mg), and styrene (520
mg) in DMF (10 mL) and Et3N (1 mL) The precipitate was washed with
EtOH to remove impurities; yield: 0.55 g (88%); yellow coloured solid;
mp 205 °C (Lit.7 mp 204–205 °C).
(E)-8-Allyl-7-hydroxy-4-methyl-6-{[4-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)phenyl]diazenyl}-2H-chromen-2-one (20)
Prepared according to the above general procedure from 4 (2.1 g, 5.25
mmol), bis(pinacolato)diboron (2.0 g, 8.0 mmol), Pd(dppf)Cl2 (0.08 g,
0.11 mmol), and dry KOAc (1.6 g, 16.0 mmol) in anhyd 1,4-dioxane
(25 mL) by heating at 80 °C for 24 h. After cooling to r.t., the reaction
mixture was poured into H2O and then extracted with CH2Cl2. The
combined organic extracts were dried (MgSO4) and concentrated in
vacuo. The residue was taken up in CH2Cl2 (5 mL) and purified by pas-
sage through a silica gel plug to afford the title compound as a dark
red-coloured solid; yield: 2.1 g (90%); mp 154–155 °C.
IR (ATR): 1405, 1413, 1586, 3011 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 3.91 (3 H, s, CH3), 7.03 (2 H, dd, J = 9, 2
Hz), 7.20 (2 H, d, J = 4 Hz), 7.31 (1 H, t, J = 7 Hz), 7.35–7.44 (2 H, m),
7.56 (2 H, d, J = 7 Hz), 7.66 (2 H, d, J = 9 Hz), 7.88–7.97 (4 H, m).
13C NMR (75 MHz, CDCl3): δ = 55.5, 114.2, 123.1, 124.7, 126.6, 127.1,
127.9, 128.7, 130, 137, 139.4, 147.1, 152, 162.
HRMS: m/z calcd for C21H19N2O [M]+: 315.1492; found: 315.1486.
1H NMR (400 MHz, CDCl3): δ = 1.50 (12 H, s), 2.43 (3 H, d, J = 1 Hz),
3.88 (2 H, d, J = 5 Hz), 4.80 (1 H, dd, J = 9, 1 Hz), 4.95 (1 H, dd, J = 17, 1
Hz), 5.91–6.10 (1 H, m), 6.40 (1 H, s, CH), 7.70–7.77 (2 H, m, CH),
7.88–7.92 (2 H, m), 8.19 (1 H, s), 11.71 (1 H, s).
8-Allyl-7-hydroxy-4-methyl-6-((E)-{4-[(E)-2-(pyridin-4-yl)vi-
nyl]phenyl}diazenyl)-2H-chromen-2-one (17)
This compound was prepared according to the above general proce-
dure from 4 (0.266 g, 0.7 mmol), Pd(OAc)2 (4 mg), PPh3 (5 mg), DMF (4
mL), 4-vinylpyridine (0.2 mL, 1.1 mmol), and Et3N (0.3 mL). The pre-
cipitate was washed with EtOH to remove impurities; yield: 0.23 g
(81%); bright red coloured solid; mp 192–194 °C.
1H NMR (400 MHz, CDCl3): δ = 2.55 (3 H, d, J = 1 Hz, CH3), 3.88 (2 H, d,
J = 5 Hz), 4.58 (2 H, dd, J = 8, 1 Hz), 5.1 (1 H, dd, J = 17, 1 Hz), 5.2 (1 H,
dd, J = 17, 1 Hz), 6.01–6.16 (1 H, m), 6.80 (2 H, d, J = 8 Hz), 7.61 (2 H, d,
J = 8 Hz), 7.69–7.75 (2 H, m), 7.85–7.89 (2 H, m), 8.19 (1 H, s), 8.55 (2
H, d, J = 8), 11.71 (1 H, s).
13C NMR (125 MHz, CDCl3): δ = 19.1, 25.1, 26.8, 86.7, 113.8, 115.2,
117.9, 121.8, 122.8, 131.2, 134.0, 136.4, 149.1, 152.0, 155.4, 166.8.
MS (ES+): m/z = 446.2 [M + H]+.
HRMS: m/z calcd for C25H27BN2O5Na [M + Na]+: 469.1942; found:
469.1939.
Ullman-Coupling Reaction; General Procedure
To the diazo compound 12 (1 equiv, 0. 340 g), CuI (30 mol%) or
chloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidenecopper(I) (5
mol%), picolinic acid (40 mol%), tribasic potassium phosphate (20
mmol), 3,5-bis(hydroxy methyl)phenol (1.2 equiv) in an oven dried
Schlenk tube under N2, was added anhyd DMSO (2 mL/equiv of sub-
strate). The reaction mixture was the heated at 120 °C for 48 h under
an atmosphere of N2. The mixture was then allowed to cool to r.t. and
then diluted by the addition of EtOAc (59 mL) and poured into H2O
(100 mL). The organic layer was separated and the aqueous layer was
extracted with EtOAc (2 × 20 mL). The combined organic extracts
were dried (MgSO4) and concentrated reduced in vacuo. The product
was purified by column chromatography (silica gel; eluent: hex-
ane/EtOAc, 1:4).
MS (ES+): m/z = 436.1 [M + H]+.
HRMS: m/z calcd for C27H21N3O3Na [M + Na]+: 458.1475; found:
458.1471.
Suzuki-Coupling Reaction; General Procedure
A mixture of the diazo compound 12 (5.25 mmol), bis(pinacolato)di-
boron (8.0 mmol), Pd(dppf)Cl2 (0.11 mmol), and dry KOAc (16.0
mmol) in anhyd 1,4-dioxane (25 mL) was heated at 80 °C for 24 h. Af-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

H
O. K. Rasheed, P. Quayle
Paper
Synthesis
(E)-1-{[4-(3,5-Bis(hydroxymethyl]phenoxy}-2-(4-methoxyphe-
nyl)diazene (22)
(2) (a) Dembitsky, V. M.; Gloriozova, T. A.; Poroikov, V. V. Natural
Products and Bioprospecting 2017, 7, 151. (b) Isabel, K.; Ulrich, L.
Synthesis 2014, 46, 2376. (c) Ventura-Camargo, B.; Marin-
Morales, M. A. TLIST (Textiles and Light Industrial Science and
Technology) 2013, 2, 85.
(3) (a) Shikhaliyeva, N. Q.; Ahmadovaa, N. Q.; Gurbanova, A. V.;
Maharramova, A. B.; Mammadovaa, G. Z.; Nenajdenkoc, V. G.;
Zubkovd, F. I.; Mahmudovb, K. T.; Pombeirob, A. J. L. Dyes Pigm.
2018, 150, 377. (b) Dong, M.; Babalhavaeji, A.; Samanta, S.;
Beharry, A. A.; Woolley, G. A. Acc. Chem. Res. 2015, 48, 2662.
(c) Bannister, W. D.; Olin, A. D.; Sting, A. H. Kirk-Othmer Encycl.
Chem. Technol. 1979, 8, 159.
To a mixture of the diazo compound 12 (1 mmol), CuI (57 mg, 30
mol%)
or
chloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-
ylidenecopper(I) (24 mg, 5 mol%), picolinic acid (50 mg, 40 mol%),
tribasic potassium phosphate (424 mg, 20 mmol), 3,5-bis(hy-
droxymethyl)phenol (21; 185 mg, 1.2 equiv) in oven-dried Schlenk
tube was added DMSO (2 mL/equiv of substrate) and the resultant re-
action mixture was heated at 120 °C for 48 h. Workup as above and
purification of the crude product by chromatography (silica gel; hex-
ane/EtOAc 1:4) afforded the tittle compound as an amorphous red solid;
yield 0.29 g (83%); mp 163–165 °C.
(4) (a) Chacko, J. T.; Subramaniam, K. Int. J. Env. Sci. 2011, 1, 1250.
(b) Dyes and Pigments: New Research; Lang, A. R., Ed.; Nova
Science Publishers: New York, 2009. (c) Delgado-Vargas, F.;
Paredes-Lopez, O. Natural Colourants for Food and Nutraceutical
Uses; CRC Press: Boca Raton, 2002. (d) Industrial Dyes: Chemis-
try, Properties, Applications; Hunger, K., Ed.; Wiley-VCH: Wein-
heim, 2003. (e) Voss, E.; Brandt, M. Eur. Pat. Appl, EP
1104674A1, 2001; Chem. Abstr. 2001, 135, 20889 (f) O’Neill, C.;
Hawkes, F. R.; Hawkes, D. L.; Lourenco, N. D.; Pinheiro, H. M.;
Delee, W. J. Chem. Technol. Biotechnol. 1999, 74, 1009.
(g) Natansohn, A.; Rochon, P.; Gosselin, J.; Xie, S. Macromole-
cules 1992, 25, 2268.
(5) (a) Rasheed, O. K. New Directions in the Chemistry of Azo-Com-
pounds, M.Phil. Thesis; University of Manchester: UK, 2011.
(b) Lawrence, A. Studies in Host-Guest Chemistry, Ph.D. Disserta-
tion; University of Manchester: UK, 2011.
(6) (a) Griess, P. J. Chem. Soc. 1865, 18, 268. (b) Griess, P. Justus
Liebigs Ann. Chem. 1860, 113, 207.
(7) Knoevenagel, E. Ber. Dtsch. Chem. Ges. 1890, 23, 2994.
(8) Rasheed, O. K.; Quayle, P.; Raftery, J. Synlett 2015, 26, 2806.
(9) Lim, Y.-K.; Lee, K.-S.; Cho, C.-G. Org. Lett. 2003, 5, 979.
(10) (a) He, L.; Freeman, H. S.; Nakpathom, M.; Boyle, P. D. Dyes Pigm.
2015, 120, 245. (b) Gasparic, J.; Novotna, M.; Jurcek, M. Collect.
Czech. Chem. Commun. 1960, 25, 2757. (c) Hnilica, L.; Gregusova,
V.; Eingegangenam, V. T. Collect. Czech. Chem. Commun. 1960,
25, 2765.
IR (ATR): 1154, 1250, 1484, 1589, 1628, 3307 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 3.86 (3 H, s), 4.51 (4 H, d, J = 5.80
Hz), 5.27 (2 H, t, J = 5.80 Hz), 6.92 (2 H, s), 7.08–7.18 (5 H, m), 7.83–
7.92 (4 H, m).
13C NMR (125 MHz, DMSO-d6): δ = 55.8, 62.6, 114.8, 115.6, 118.7,
102.2, 124.5, 124.6, 145.2, 146.4, 147.8, 155.9, 161.9.
MS (ES+): m/z = 347.
HRMS: m/z calcd for C25H21N2O4 [M + H]+: 347.4019; found: 347.4020.
(E)-8-Allyl-6-({4-[3,5-bis(hydroxymethyl)phenoxy]phenyl}diaze-
nyl)-7-hydroxy-4-methyl-2H-chromen-2-one (23)
Prepared according to the above procedure using the diazo compound
4; yield: 0.37 g (83%); red coloured solid; mp 184–185 °C.
1H NMR (400 MHz, CDCl3): δ = 2.51 (3 H, s), 3.87 (2 H, d, J = 5 Hz), 4.51
(2 H, d, J = 7 Hz), 4.90 (1 H, dd, J = 9, 1 Hz), 5.11 (1 H, dd, J = 11, 1 Hz),
5.25 (1 H, dd, J = 16 Hz), 5.92–6.03 (1 H, m), 7.28–7.32 (1 H, m), 7.40–
7.45 (1 H, m), 7.77–7.81 (1 H, m, CH), 7.92–7.96 (2 H, m, CH), 8.09 (1
H, s, CH), 11.51 (1 H, s).
13C NMR (125 MHz, CDCl3): δ = 19.1, 25.0, 69.6, 108.1, 109.2, 110.1,
119.8, 121.9, 126.8, 130.6, 131.2, 136.4, 139.7, 140.9, 149.1, 152.0,
153.4, 160.8.
MS (ES+): m/z = 457.1 [M + H]+.
HRMS: m/z calcd for C27H24N2O5Na [M + Na]+: 479.1577; found:
(11) (a) Jogi, P. S.; Meshram, J.; Sheikh, J.; Hadda, T. B. Med. Chem.
Res. 2013, 22, 4202. (b) Shahinian, E. G. H.; Haiduc, I.; Sebe, I. U.
P. B. Sci. Bull. 2011, 73, 153. (c) Rana, A.; Munawar, M. A.;
Rehman, S.; Muhammad, N. Pak. J. Sci. Ind. Res. 2009, 52, 117.
(d) Yazdanbakhsh, M. R.; Ghanadzadeh, A.; Moradi, E. J. Mol. Liq.
2007, 136, 165.
(12) Nolan, K. A.; Doncaster Dunstan, M. S.; Scott, K. A.; Frenkel, A.
D.; Siegel, D.; Ross, D.; Barnes, J.; Levy, C.; Leys, D.; Whitehead,
R. C.; Stratford, I. J.; Bryce, R. A. J. Med. Chem. 2009, 52, 7142.
(13) Oakes, J.; Gratton, P. J. Chem. Soc., Perkin Trans. 2 1998, 1857.
(14) (a) Struebe, J.; Gates, P. J.; Staubitz, A. J. Org. Chem. 2014, 79,
1719. (b) Martínez-Estibalez, U.; Sotomayor, N.; Lete, E. Tetrahe-
dron Lett. 2007, 48, 2919. (c) Harvey, J. H.; Butler, B. K.; Trauner,
D. Tetrahedron Lett. 2007, 48, 1661.
(15) For example, see: (a) Yin, S.; Xu, H.; Shi, W.; Gao, Y.; Song, Y.;
Tang, B. Z. Dyes Pigm. 2007, 73, 285. (b) Su, X.; Guang, S.; Xu, H.;
Yang, J.; Song, Y. Dyes Pigm. 2010, 87, 69. (c) Adachi, M.; Bredow,
T.; Jug, K. Dyes Pigm. 2004, 63, 225. (d) Jeoung, C-B.; Haak, O.;
Grahn, W.; Boldt, P. J. Prakt. Chem. 1993, 335, 521. (e) Berbreiter,
D. E.; Osburn, P. L.; Li, C. Org. Lett. 2002, 4, 737.
479.1576.
Funding Information
We thank the University of Manchester for support. The University of
Manchester thanks the EPSRC (EP/K039547/1) for the provision of
Bruker NMR spectrometers. O.K.R. also thanks the University of Mon-
tana for support.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591571.
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References
(1) (a) Sahoo, J.; Paidesetty, S. K. Asian J. Pharm. Clin. Res. 2016, 9,
33. (b) Filarowski, A. Resonance 2010, 15, 850. (c) Rueck-Braun,
K.; Dietrich, S.; Kempa, S.; Priewisch, B. Azoarenes, In Science of
Synthesis;3V1o.bl Ramsden, C. A.; Bellus, D., Eds.; Georg Thieme Verlag:
Stuttgart, 2007, 1425–1537.
(16) (a) Anger, E.; Fletcher, S. P. Eur. J. Org. Chem. 2015, 3651.
(b) Rauf, M. A.; Hisaindee, S.; Saleh, N. RSC Adv. 2015, 5, 18097.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

I
O. K. Rasheed, P. Quayle
Paper
Synthesis
(17) (a) Rasheed, O. K.; McDouall, J. J. W.; Muryn, C. A.; Raftery, J.;
Victorica-Yrezabal, I. J.; Quayle, P. Dalton Trans. 2017, 46, 5229.
(b) Rasheed, O. K.; Lawrence, A.; Quayle, P.; Bailey, P. D. Synlett
2016, 27, 905.
(18) (a) Chattopadhyay, S. K.; Mondal, P.; Ghosh, D. Synthesis 2014,
46, 3331. (b) Bull, J. Ph.D. Thesis; University of Manchester: UK,
2008.
(19) (a) Al-Hamdani, U.; Gassim, T. E.; Radhy, H. H. Molecules 2010,
15, 5620. (b) Siemeling, U.; Bruhn, C.; Bretthauer, F.; Borg, M.;
Traeger, F.; Vogel, F.; Azzam, W.; Badin, M.; Strunskus, T.; Woell,
C. Dalton Trans. 2009, 40, 8593. (c) Lillian, J.; Bryan, R.; Piotr, K.
Liq. Cryst. 2009, 36, 179. (d) Dyer, D. J.; Lee, V. Y.; Twieg, J. R. Liq.
Cryst. 1997, 23, 551. (e) Silong, S.; Lutfor, M. R.; Rahman, M. Z.;
Yunus, W. M. Z.; Haron, M. J.; Ahmad, M. B.; Yusoff, W. M. D.
J. Appl. Polym. Sci. 2002, 86, 2653.
(20) Weickhardt, B.; Siegrist, A. E. Helv. Chim. Acta 1972, 55, 138.
(21) Janus, K.; Matczyszyn, K.; Sworakowski, J.; Biernat, J. F.;
Galewski, Z. Molecular Crystals and Liquid Crystals Science and
Technology 2001, 361, 143.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I