Palladium-Catalyzed Oxidative Synthesis of Unsymmetrical Azophenols

Article abstract of DOI:10.1021/acs.joc.5b02614

A straightforward palladium-catalyzed oxidative hydroxylation of azobenzenes is reported. The developed methodology tolerates various functional groups and allows the synthesis of diverse unsymmetrical azophenols under mild conditions in good to excellent yields. A complementary procedure was also investigated by in situ generation of PIFA. This study represents the first general method for the synthesis of o-hydroxyazobenzenes starting from simple azoarenes.

Full text of DOI:10.1021/acs.joc.5b02614

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Article
Palladium-Catalyzed Oxidative Synthesis of Unsymmetrical Azophenols
Thi Hong Long NGUYEN, Nicolas Gigant, Sandrine Delarue-Cochin, and Delphine Joseph
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02614 • Publication Date (Web): 08 Feb 2016
Downloaded from http://pubs.acs.org on February 9, 2016
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Palladium-Catalyzed Oxidative Synthesis of Unsymmetrical Azophenols
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Thi Hong Long Nguyen,‡ Nicolas Gigant,‡ Sandrine DelarueꢀCochin, and Delphine Joseph*
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BioCIS, Université ParisꢀSud, CNRS, Université ParisꢀSaclay, Fꢀ92296 ChâtenayꢀMalabry,
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France.
*delphine.joseph@uꢀpsud.fr
Abstract Graphic
Abstract
A straightforward palladiumꢀcatalyzed oxidative hydroxylation of azobenzenes is reported.
The developed methodology tolerates various functional groups and allows the synthesis of
diverse unsymmetrical azophenols under mild conditions in good to excellent yields. A
complementary procedure was also investigated by in situ generation of PIFA. This study
represents the first general method for the synthesis of orthoꢀhydroxy azobenzenes starting
from simple azoarenes.
Introduction
Aromatic azo compounds are important scaffolds and find application in many fields due to
their unique properties based on light triggered switches.1 They are mainly involved in protein
probes,2 organic dyes,3 chemosensors,4 smart surface materials,5 polymers6 and molecular
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machines.7 Given the broad utility of azobenzenes, the development of useful methods for
their preparation are keenly pursued.8 However, no efficient synthesis of orthoꢀazophenol
frameworks has been developed. As depicted in Figure 1, these privileged structures possess
various useful applications: for example, the azo dye A has been approved as a synthesized
food colorant by the FDA. The azophenol B has been used as an azoꢀlinker for mediating
peptide cyclization9 whereas the fluorescence properties of 2ꢀborylazobenzenes such as C
have been recently explored.10 In addition, knowing that the incorporation of an hydroxyl
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group in arenes can significantly affect their original physical and chemical properties,11
a
general, mild and direct catalytic route to introduce this versatile functional group would be
highly attractive.
Figure 1. Representative oꢀAzophenol Derivatives
CꢀH bond transformations have attracted widespread attention as powerful and ideal
reactions.12 Indeed, the ability to directly oxidize carbon hydrogen bonds into carbon
heteroatom bonds is very useful for the lateꢀstage functionalization of complex molecules or
to rapidly increase the molecular diversity.13 Over the past decade, there has been significant
progress in the development metalꢀcatalyzed CꢀH oxidation, and recently, several rutheniumꢀ
or palladiumꢀcatalyzed protocols have been established for hydroxylation in the presence of
strong or weak coordinating directing groups.14 In addition, orthoꢀfunctionalization of
azobenzenes has been investigated toward various coupling partners.15 During our study,
Chakraborti and coꢀworkers have developed a practical palladiumꢀcatalyzed aryl
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hydroxylation by employing dioxane as a source of hydroxyl radicals.16 If the protocol was
mainly very efficient with a range of benzoxazoles and benzothiazoles as directing groups,
this latter was limited and unselective starting from simple azobenzenes due to the generation
of the corresponding azoxybenzenes. Therefore, the need for methodology that can address
this drawback remains a challenge. Inspired by a seminal work reported by Sanford and coꢀ
workers17 and other previous studies,18 we reasoned that hypervalent iodine reagents could be
highly attractive for the synthesis of orthoꢀazophenols starting from simple azoarenes. We
focused a particular attention in developing an operationally simple process involving mild
reaction conditions. In this way, we shaped an easy and general route for the oxidative
preparation of azophenol compounds. This synthetic method is far more direct and efficient
than the rare and narrow previously reported procedures which are mainly based on the
Wallach rearrangement.10,16,19
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Results and Discussion
The present study was initiated starting from the valuable dibromo azobenzene 1a, which will
allow chemical modulations for the introduction of designed molecular anchors.20 Firstly, 1a
was treated with
5
mol
%
Pd(OAc)2 and 1.5 equiv of oxidant, the
[bis(trifluoroacetoxy)iodo]benzene (PIFA), in 1,2ꢀdichloroethane (DCE) at 70 °C under air
atmosphere (Table 1, entry 1). Fruitfully, the targeted azophenol 2a was isolated in an
encouraging 41% yield. A screening of the PIFA loading increases the yield of the reaction up
to 67% by using 2 equiv of the hypervalent iodine reagent (Table 1, entries 2ꢀ3). The
utilization of K2S2O8 or oxone as alternative oxidant did not promote the reaction and the
starting material 1a was recovered. Importantly, a control experiment in the absence of metal
yielded no product and resulted in the recovery of the starting material. Further optimization
indicated that 5 mol% of Pd(OAc)2 is the best loading to fully convert 1a without significant
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degradation (Table 1, entries 4ꢀ7 vs 2). Surprisingly, albeit pyridine is known to increase the
rate of the C–H oxygenation of arenes,21 this nitrogenꢀcontaining ligand totally inhibited the
reaction (Table 1, entry 8). Moreover, considering the importance of influencing the
electrophilicity of the palladium(II) catalyst,22 the oxidative reaction was carried out in the
presence of 1 equiv of AcOH or TFA, but none of them enhanced the yield of 2a (Table 1,
entries 9ꢀ11). Increasing or decreasing the temperature of the reaction did not lead to any
additional improvements in the yield (Table 1, entries 12ꢀ13). Besides, the nature of solvent is
also a critical factor in this reaction type. Although CH3CN, dioxane or CH3NO2 have been
commonly employed as efficient solvents in PdII/PdIVꢀcatalyzed CꢀH oxidation, they were
absolutely not suitable in our case. Indeed, due to the lack of solubility of 1a in CH3CN and
CH3NO2, and the absence of conversion in the presence of dioxane, the use of DCE was
considered of prime importance to reach the reaction.
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Table 1. Optimization of the Reaction Conditionsa
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entry
Cat. [Pd]
(mol%)
PIFA (equiv) additive
(mol%)
T (°C)
yieldb
(%)
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0
1
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (2.5)
Pd(OAc)2 (7.5)
1.5
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ꢀ
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2
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PdCl2(CH3CN)2 (5)
Pd(TFA)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(TFA)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
2
ꢀ
7
2
ꢀ
8
2
pyridine (5)
9
2
AcOH (100) 70
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2
TFA (100)
70
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60
80
46
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41
2
TFA (100)
2
ꢀ
ꢀ
2
aReaction conditions: 1a (0.20 mmol) under the appropriate reaction conditions (c = 0.2
mol.Lꢀ1). bIsolated yield.
We next explored the scope and limitations of this system under the optimized reaction
conditions (Scheme 1). Gratifyingly, the reaction is tolerant toward a variety of p,p’ꢀ
disubstituted azobenzenes and showed good compatibility with a wide range of valuable
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functional groups such as halogen atoms (2aꢀ2c). Electronꢀwithdrawing groups on the
aromatic ring slightly affected the yield of the reaction (2dꢀ2f). Notably, the moderately
deactivating ester substituent proved to be the best functionality, leading to the scaffold 2e in
an excellent 93% yield. Similarly, substrates bearing an electronꢀdonating group such as a pꢀ
methoxy or a pꢀphenyl moiety underwent hydroxylation to give the corresponding
unsymmetrical aromatic azo compounds 2g and 2h in good yields. Alternatively, the
optimized conditions could be applied to a substituentꢀexempt azobenzene, providing the
desired product 2i in a 81% yield. We next examined the reactivity of various symmetrical
m,m’ꢀdisubstituted azobenzenes. Starting from haloꢀsubstituted scaffolds 1j and 1k, the
reaction mainly occurred at the sterically less hindered position affording two regioisomers
with reasonable selectivities (2j and 2k). Contrariwise, the symmetrical mꢀmethoxy
azobenzene 1l led to 2l with a modest 35% yield but with a complete selectivity. In this
particular case, 1.2 equiv of PIFA were employed even if roughly 20% of 1l was recovered.
Indeed, degradation was unexpectedly observed following our previous conditions or
attempting sequential additions of PIFA. We first speculated that the low yield might result
from the potential formation of highly reactive radical cations. Nevertheless, using degassed
DCE under argon in dark conditions did not permit to enhance the reaction yield (30%). The
versatility of the reaction was further demonstrated by the fact that more sterically hindered
azobenzenes are also compatible (2mꢀ2o). Although a slight increase of the catalyst loading
was sometimes necessary for obtaining good conversions, 2m, 2n and 2o were isolated in
moderate yields. However, it’s worth mentioning that the synthesis of densely substituted
azoarenes is usually not an easy task.
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Scheme 1. Substrate Scope of Symmetrical Azobenzenesa,b
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aUnless otherwise noted, reaction conditions: 1 (1 equiv), PIFA (2 equiv), Pd(OAc)2 (5
b
c
mol%) in DCE (c = 0.2 mol.Lꢀ1) at 70 °C. Isolated yield. PIFA (1.2 equiv). dPd(OAc)2 (7.5
mol%).
These results encouraged us to further survey the scope of this oxidative reaction with respect
to unsymmetrical azobenzene derivatives (Scheme 2). When the reaction was carried out with
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oꢀmonosubstituted unsymmetrical azos 1p and 1q bearing a weakly deactivating halogen
atom, two regioisomers were isolated with satisfying selectivities up to 78:22 (2p and 2q).
Each time, the ortho position of the unsubstituted aromatic ring was preferentially
hydroxylated. Gratifyingly, starting from o,pꢀdihalogenated unsymmetrical azo 1r, the desired
azophenol 2r was formed as a single regioisomer. Other simple pꢀmonosubstituted substrates
such as 1t and 1u reacted efficiently, furnishing respectively 2t and 2u as the major products.
If the regioselectivity was preserved with the methoxylated compound 1s, degradation
explained once more the low yield observed even in the presence of a reduced amount of
PIFA. Interestingly, we were pleased to find that the regioselectivity of the hydroxylation was
increased starting from fluorinated scaffold 1v, leading to 2v in an excellent 92:08
regioisomers ratio. To gauge the substituent electronic effect on the regioselectivity, the
reaction was performed with the pushꢀpull derivative 1w. A low selectivity was observed,
highlighting that the regioselectivity is mainly controlled by the steric hindrance of the
starting material.
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Scheme 2. Substrate Scope of Unsymmetrical Azobenzenesa,b
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aUnless otherwise noted, reaction conditions: 1 (1 equiv), PIFA (2 equiv), Pd(OAc)2 (5
mol%) in DCE (c = 0.2 mol.Lꢀ1) at 70 °C. bIsolated yield. cPIFA (1.2 equiv).
Finally, to obtain mechanistic information, we evaluated the intramolecular isotope effect
starting from an equimolar mixture of 1i and [D10]ꢀ1i. Moderate primary isotope effect (kH/kD
= 1.42) was measured (Scheme 3, eq 1).
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Scheme 3. Evaluation of Deuterium Isotope Effect
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A similar magnitude to the product ratio was confirmed with the intermolecular isotope effect
starting from [D5]ꢀ1i (kH/kD = 1.54) (Scheme 3, eq 2), indicating that the aromatic CꢀH bond
cleavage by Pd may be involved in the rate determining step of the reaction.
Aware of the fact that PIFA produces equimolar amounts of iodobenzene as byproducts, we
decided to explore the feasibility of a catalytic version of the hydroxylation of azobenzenes by
in situ generation of PIFA (Scheme 4). A survey of various reaction conditions revealed after
optimization that 2e can be satisfying isolated by using 20 mol% of iodobenzene with oxone
(2 equiv) in the presence of TFA as cosolvent.23 Following this modified oxidative procedure,
azophenols 2b and 2i were then also obtained in moderate yields.
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Scheme 4. Synthesis of azophenols by in situ generation of PIFAa,b
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Pd(OAc)2 (5 mol%)
PhI (20 mol%)
oxone (2 equiv)
R1
R1
N
N
N
N
DCE:TFA (1:1)
70 °C
R1
Cl
R1
9
1
OH
2
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COOEt
Cl
N
N
N
N
N
N
OH
OH
EtOOC
OH
2e (57%)
2b (21%)
2i (43%)
aUnless otherwise noted, reaction conditions: 1 (1 equiv), PhI (20 mol%), oxone (2 equiv),
Pd(OAc)2 (5 mol%) in DCE (c = 0.2 mol.Lꢀ1) at 70 °C. bIsolated yield.
The proposed catalytic cycle is depicted in Scheme 5 on the basis of the above observations
and the previous literature.14,15 CꢀH activation of the arene substrate gives a fiveꢀmembered
palladacycle intermediate with concomitant loss of AcOH. Oxidative addition of PIFA to this
arylpalladium(II) intermediate would then generate a Pd(IV) species, releasing iodobenzene
and trifluoacetic acid. Although a reaction mechanism involving a PdII/PdIV process for this
system is proposed, an alternative PdII/PdIII catalytic cycle through a bimetallic Pd(III)
complex could be also envisaged.24 Subsequent reductive elimination leads the targeted
trifluoroꢀacylated azophenol with concomitant regeneration of the active catalyst. The final
product is then obtained after simple hydrolysis on silica gel. In the iodobenzene catalytic
version of the reaction, the PIFA is in situ generated in the presence of iodobenzene and oxone
in trifluoroacetic acid.
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Scheme 5. Plausible Mechanism of the Reaction
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Conclusion
In summary, we have developed a practical and efficient method for the straightfoward orthoꢀ
directed hydroxylation of azobenzenes under mild conditions. The reaction showed very good
functional groups tolerance, leading to a wide range of original and unsymmetrical
azophenols in satisfying to high yields. In addition, our procedure was extended to the in situ
generation of PIFA in the presence of catalytic amount of iodobenzene. Ongoing efforts are
directed toward the application of this methodology to the synthesis of azophenols with
potential photoswitching and fluorescence proprieties.
Experimental Section
General Information. Reagents were purchased as reagent grade and were used without
further purification other than those aboveꢀmentioned. Prior to use, toluene and
dichloromethane were dried by means of a solvent purifier system. All anhydrous reactions
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were carried out under argon atmosphere. H NMR and C NMR were recorded on a 300
MHz spectrometer in CDCl3 or C6D6 at 25°C. Chemical shifts values are given in ppm
downfield from tetramethylsilane (TMS) with the chloroform resonance as the internal
standard. The following abbreviations were used to describe peak splitting patterns when
appropriate: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of
doublet, dt = doublet of triplet, td = triplet of doublet, dq = doublet of quarter. Coupling
constants (J) are reported in Hz and refer to apparent peak multiplications. Mass spectra and
high resolution mass spectra were obtained with a QꢀTOF micro spectrometer using ESI.
Melting points are uncorrected and were recorded on a micromelting point apparatus. Infrared
(IR) spectra were recorded as neat films. Analytical thin layer chromatography was performed
on 60Fꢀ254 precoated silica (0.2 mm) on glass and was revealed by UV light or by spraying
with a potassium permanganate solution, followed by charring at 150 °C. Flash
chromatography separations were carried out on silica gel (40ꢀ63µm).
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Preparation of Starting Azobenzenes
Symmetric and asymmetric aromatic azobenzene derivatives were prepared according to the
literature procedures.25,26,27
General Procedure for Symmetric Azobenzenes25
To a solution of amine (0.40 mmol) in toluene (8 mL) was added activated manganese (IV)
oxide (348 mg, 4.00 mmol). The mixture was then heated at reflux for 2 h and formed water
was removed with a DeanꢀStark apparatus. The reaction mixture was filtered through Celite®
pad before washing it three times with toluene. After evaporation of the solvent under reduced
pressure, products are purified by recrystallization in cyclohexane.
(E)-1,2-Bis(3,5-dichlorophenyl)diazene (1m). Yield 88% (112 mg); orange solid, mp 197ꢀ
198 °C; IR (neat, cmꢀ1) 3083, 1566, 1424, 1235, 1207, 1097, 929, 891, 837, 620; H NMR
1
13
(300 MHz, CDCl3) δ 7.83 (d, J = 1.9 Hz, 4H), 7.52 (t, J = 1.9 Hz, 2H); C NMR (75 MHz,
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CDCl3) δ 153.1 (2×C), 135.8 (4×C), 131.3 (2×CH), 121.8 (4×CH); HRMS (TOFꢀESI) m/z:
Calcd for C12H6N2Cl4 [M]ꢀ 317.9291, found 317.9316.
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(E)-1,2-Bis(2-chloro-4-methylphenyl)diazene (1n). Yield 70% (78 mg); orange solid, mp
177ꢀ178 °C; IR (neat, cmꢀ1) 1595, 1445, 1210, 1056, 889, 835, 686; 1H NMR (300 MHz,
CDCl3) δ 7.72 (d, J = 8.3 Hz, 2H), 7.39 (t, J = 1.2 Hz, 2H), 7.15 (dd, J = 8.3 Hz, J = 1.2 Hz,
2H), 2.43 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 146.8 (2×C), 143.0 (2×C), 135.6 (2×C),
131.0 (2×CH), 128.2 (2×CH), 117.7 (2×CH), 21.3 (2×CH3); HRMS (TOFꢀESI) m/z: Calcd for
C14H13N2Cl2 [M + H]+ 279.0450, found 279.0460.
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General Procedure for Dissymmetric Azobenzenes 26,27
Nitrosobenzene derivative (0.80 mmol) was dissolved in glacial acetic acid (2 mL) and the
amine (0.80 mmol) in EtOH (0.5 ml) was added to the solution. After stirring for 6 hours at 40
°C, the mixture was poured on ice and filtered. The crude brown product was then purified by
column chromatography with silica and cyclohexane/ethyl acetate (98:2 to 80:20).
(E)-1-(2-Chlorophenyl)-2-phenyldiazene (1o). 1o was prepared following the general
procedure using nitrosobenzene (86 mg, 0.80 mmol) and 2ꢀchloroaniline (100 mg, 0.80
mmol). Yield 45% (78 mg); orange liquid; IR (neat, cmꢀ1) 3071, 1585, 1448, 1256, 1222,
1150, 1057, 926, 769, 753, 716, 684; 1H NMR (300 MHz, CDCl3) δ 8.02 (dd, J = 8.0 Hz, J =
2.1 Hz, 2H), 7.74 (dd, J = 7.6 Hz, J = 2.1 Hz, 1H), 7.61ꢀ7.53 (m, 4H), 7.44ꢀ7.34 (m, 2H); 13C
NMR (75 MHz, CDCl3) δ 152.8 (C), 148.7 (C), 135.3 (C), 131.7 (CH), 131.6 (CH), 130.7
(CH), 129.2 (2×CH), 127.3 (CH), 123.4 (2×CH), 117.6 (CH).; HRMS (TOFꢀESI) m/z: Calcd
for C12H10N2Cl [M + H]+ 217.0527, found 217.0534.
(E)-1-(4-Bromo-2-chlorophenyl)-2-phenyldiazene (1r). 1r was prepared following the
general procedure using nitrosobenzene (86 mg, 0.80 mmol) and 2ꢀchloroꢀ4ꢀbromoaniline
(165 mg, 0.80 mmol). Yield 40% (94 mg); orange solid, mp 92ꢀ93 °C; IR (neat, cmꢀ1) 3077,
1
3054, 1570, 1484, 1455, 1374, 1220, 1183, 1085, 1053, 865, 824, 766, 711, 615; H NMR
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(300 MHz, CDCl3) δ 8.00ꢀ7.96 (m, 2H), 7.76 (d, J = 1.7 Hz, 1H), 7.63 (d, J = 8.6 Hz, 1H),
7.57ꢀ7.54 (m, 3H), 7.49 (dd, J = 8.7 Hz, J = 1.7 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 152.6
(C), 147.6 (C), 136.3 (C), 133.3 (CH), 131.8 (CH), 130.6 (CH), 129.2 (2×CH), 125.2 (C),
123.4 (2×CH), 118.6 (CH); HRMS (TOFꢀESI) m/z: Calcd for C12H9N2ClBr [M + H]+
296.9611, found 296.9617.
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Ethyl (E)-4-[(4-methoxyphenyl)diazenyl]benzoate (1w). 1w was prepared following the
general procedure using ethyl 4ꢀnitrosobenzoate (143 mg, 0.80 mmol) and 4ꢀmethoxyaniline
(99 mg, 0.80 mmol). Yield 75% (170 mg); orange solid, mp 103ꢀ104 °C; IR (neat, cmꢀ1) 3006,
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2843, 1703, 1601, 1582, 1499, 1401, 1270, 1246, 1184, 1123, 881, 862, 774, 692; H NMR
(300 MHz, CDCl3) δ 8.20 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 8.9 Hz, 2H), 7.92 (d, J = 8.5 Hz,
2H), 7.05 (d, J = 8.9 Hz, 2H), 4.43 (q, J = 7.1 Hz, 2H), 3.93 (s, 3H), 1.45 (t, J = 7.1 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 166.1 (C), 162.6 (C), 155.3 (C), 147.0 (C), 131.6 (C), 130.5
(2×CH), 125.2 (2×CH), 122.3 (2×CH), 114.3 (2×CH), 61.2 (CH2), 55.6 (CH), 14.3 (CH3);
HRMS (TOFꢀESI) m/z: Calcd for C16H17N2O3 [M + H]+ 285.1234, found 285.1238.
General Procedure for the Direct Palladium-Catalyzed Synthesis of Unsymmetrical
Azophenols
A mixture of azobenzene 1 (0.20 mmol), [bis(trifluoroacetoxy)iodo]benzene (0.40 mmol),
Pd(OAc)2 (2.2 mg, 5 mol%) in dichloroethane (1 mL) was stirred at 70 °C until the
disappearance of the starting material followed by TLC. After cooling to room temperature,
the solvent was removed under vacuum. The crude product was then purified over a column
of silica gel using cyclohexane and ethyl acetate (100:0; 98:2; 95:5; 90:10) as the eluent to
afford the desired product 2.
(E)-5-Bromo-2-[(4-bromophenyl)diazenyl]phenol (2a). 2a was prepared following the
general procedure for 7 h. Yield 67% (48 mg); orange solid, mp 182ꢀ183 °C; IR (neat, cmꢀ1)
3081, 2959, 2851, 1600, 1571, 1559, 1443, 1410, 1298, 1256, 1175, 1066, 1003, 835, 804; 1H
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NMR (300 MHz, CDCl3) δ 12.85 (s, 1H, OH), 7.76 (d, J = 8.8 Hz, 2H), 7.71 (s, 1H), 7.65 (d,
J = 8.8 Hz, 2H), 7.21 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 153.5 (C), 149.3 (C), 136.4 (C),
134.4 (CH), 132.9 (2×CH), 127.9 (C), 126.1 (C), 123.9 (2×CH), 123.8 (CH), 121.7 (CH);
HRMS (TOFꢀESI) m/z: Calcd for C12H7N2OBr2 [M − H]− 354.8911, found 354.8905.
(E)-5-Chloro-2-[(4-chlorophenyl)diazenyl]phenol (2b). 2b was prepared following the
general procedure for 3 h. Yield 86% (46 mg); orange solid, mp 172ꢀ173 °C; IR (neat, cmꢀ1)
3085, 2925, 1887, 1750, 1601, 1564, 1475, 1451, 1385, 1301, 1257, 1078, 1005, 944, 895,
839, 808, 776; 1H NMR (300 MHz, CDCl3) δ 12.92 (s, 1H, OH), 7.88ꢀ7.82 (m, 3H), 7.52 (d, J
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= 8.7 Hz, 2H), 7.09ꢀ7.06 (m, 2H); C NMR (75 MHz, CDCl3) δ 153.5 (C), 148.8 (C), 139.2
(C), 137.4 (C), 136.0 (C), 134.1 (CH), 129.7 (2×CH), 123.5 (2×CH), 120.7 (CH), 118.4 (CH);
HRMS (TOFꢀESI) m/z: Calcd for C12H7N2OCl2 [M − H]− 264.9941, found 264.9934.
(E)-5-Fluoro-2-[(4-fluorophenyl)diazenyl]phenol (2c). 2c was prepared following the
general procedure for 6 h. Yield 66% (31 mg); orange solid, mp 124ꢀ125 °C; IR (neat, cmꢀ1)
3083, 2953, 1593, 1501, 1495, 1463, 1428, 1398, 1356, 1310, 1281, 1232, 1142, 1107, 979,
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840, 772, 754; H NMR (300 MHz, CDCl3) δ 13.17 (d, J = 1.4 Hz, 1H, OH), 7.94ꢀ7.86 (m,
3H), 7.27ꢀ7.20 (m, 2H), 6.80 (td, J = 8.3 Hz, JHꢀF = 8.0 Hz, J = 2.4 Hz, 1H), 6.73 (dd, JHꢀF
=
10.3 Hz, J = 2.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 165.1 (d, JCꢀF = 254.3 Hz, C), 164.3
(d, JCꢀF = 251.2 Hz, C), 155.0 (d, JCꢀF = 14.3 Hz, C), 146.7 (C), 135.09 (d, JCꢀF = 11.3 Hz,
CH), 126.9 (C), 124.1 (d, JCꢀF = 9.0 Hz, 2×CH), 116.5 (d, JCꢀF = 22.5 Hz, 2×CH), 108.0 (d, JCꢀ
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= 23.3 Hz, CH), 104.9 (d, JCꢀF = 24.8 Hz, CH); F NMR (188 MHz, CDCl3) δ ꢀ101.58, ꢀ
F
106.58; HRMS (TOFꢀESI) m/z: Calcd for C12H9N2OF2 [M + H]+ 235.0677, found 235.0676.
(E)-5-Trifluoromethyl-2-[(4-trifluoromethylphenyl)diazenyl]phenol (2d). 2d was
prepared following the general procedure for 48 h. Yield 35% (23 mg); orange solid, mp 121ꢀ
122 °C; IR (neat, cmꢀ1) 2924, 1593, 1503, 1459, 1425, 1317, 1216, 1172, 1121, 1010, 952,
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903, 850, 829, 795, 745, 672; H NMR (300 MHz, CDCl3) δ 12.60 (s, 1H, OH), 8.12 (d, J =
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8.3 Hz, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.83 (d, J = 8.3 Hz, 2H), 7.36 (m, 2H); C NMR (75
MHz, CDCl3) δ 152.5 (C), 152.2 (C), 138.4 (C), 135.0 (q, JCꢀF = 32.4 Hz, C), 134.1 (CH),
133.3 (q, JCꢀF = 32.4 Hz, C), 126.7 (d, JCꢀF = 3.5 Hz, 2×CH), 123.6 (q, JCꢀF = 271.0 Hz, C),
123.2 (q, JCꢀF = 271.4 Hz, C), 122.8 (2×CH), 116.7 (d, JCꢀF = 3.3 Hz, CH), 116.1 (d, JCꢀF = 3.6
Hz, CH); 19F NMR (188 MHz, CDCl3) δ ꢀ60.92, ꢀ61.55; HRMS (TOFꢀESI) m/z: Calcd for
C14H7N2OF6 [M − H]− 333.0468, found 333.0449.
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Ethyl (E)-4-[(4-ethoxycarbonylphenyl)diazenyl]-3-hydroxybenzoate (2e). 2e was
prepared following the general procedure for 10 h. Yield 93% (64 mg); orange solid, mp 157ꢀ
159 °C; IR (neat, cmꢀ1) 2962, 1717, 1572, 1491, 1421, 1366, 1307, 1276, 1258, 1222, 1210,
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1149, 1084, 1007, 960, 870, 791, 773, 756, 690; H NMR (300 MHz, CDCl3) δ 12.62 (s, 1H,
OH), 8.24 (d, J = 8.4 Hz, 2H), 8.08 (d, J = 8.1 Hz, 1H), 7.98 (d, J = 8.4 Hz, 2H), 7.76 (m,
2H), 4.49ꢀ4.40 (m, 4H), 1.46 (t, J = 7.1 Hz, 3H), 1.45 (t, J = 7.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 165.6 (CO), 165.4 (CO), 153.2 (C), 152.2 (C), 139.5 (C), 134.7 (C), 133.3 (CH),
132.8 (C), 130.8 (2×CH), 122.3 (2×CH), 120.8 (CH), 120.0 (CH), 61.5 (CH2), 61.4 (CH2),
14.3 (2×CH3); HRMS (TOFꢀESI) m/z: Calcd for C18H19N2O5 [M + H]+ 343.1288, found
343.1302.
(E)-5-Trifluoromethoxy-2-[(4-trifluoromethoxyphenyl)diazenyl]phenol (2f). 2f was
prepared following the general procedure for 32 h. Yield 58% (42 mg); orange solid, mp 70ꢀ
71 °C; IR (neat, cmꢀ1) 2958, 1755, 1679, 1589, 1500, 1428, 1400, 1361, 1251, 1150, 990, 924,
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848, 820, 701; H NMR (300 MHz, CDCl3) δ 12.94 (s, 1H, OH), 7.98 (d, J = 8.8 Hz, 1H),
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7.93 (d, J = 8.8 Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H); 6.92 (m, 2H); C NMR (75 MHz, CDCl3)
δ 154.2 (C), 152.3 (C), 151.2 (C), 148.4 (C), 135.6 (C), 134.8 (CH), 123.8 (2×CH), 121.6
(2×CH), 120.4 (q, JCꢀF = 256.9 Hz, C), 120.3 (q, JCꢀF = 257.6 Hz, C), 112.0 (CH), 109.7 (CH);
19F NMR (188 MHz, CDCl3) δ ꢀ55.61, ꢀ55.89; HRMS (TOFꢀESI) m/z: Calcd for
C14H7N2O3F6 [M − H]− 365.0366, found 365.0363.
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(E)-5-Methoxy-2-[(4-methoxyphenyl)diazenyl]phenol (2g). 2g was prepared following
the general procedure for 24 h. Yield 54% (28 mg); orange solid, mp 137ꢀ138 °C; IR (neat,
cmꢀ1) 2928, 2837, 1611, 1579, 1503, 1451, 1435, 1397, 1314, 1281, 1251, 1207, 1197, 1147,
1106, 1023, 966, 928, 831, 804, 765, 641; 1H NMR (300 MHz, CDCl3) δ 13.73 (br., 1H, OH),
7.81 (d, J = 9.0 Hz, 2H), 7.78 (d, J = 8.8 Hz, 1H), 7.02 (d, J = 9.0 Hz, 2H), 6.62 (dd, J = 8.8
Hz, J = 2.6 Hz, 1H), 6.51 (d, J = 2.6 Hz, 1H), 3.90 (s, 3H), 3.89 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 163.3 (C), 161.5 (C), 155.7 (C), 144.3 (C), 134.1 (CH), 132.7 (C), 123.3 (2×CH),
114.5 (2×CH), 107.8 (CH), 101.4 (CH), 55.7 (CH3), 55.6 (CH3); HRMS (TOFꢀESI) m/z:
Calcd for C14H15N2O3 [M + H]+ 259.1077, found 259.1081.
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(E)-4-{[(1,1'-Biphenyl)-4-yl]diazenyl}-(1,1'-biphenyl)-3-ol (2h). 2h was prepared
following the general procedure for 10 h. Yield 76% (53 mg); orange solid, mp 228ꢀ229 °C;
IR (neat, cmꢀ1) 3036, 1618, 1559, 1505, 1479, 1433, 1411, 1383, 1358, 1334, 1253, 1205,
1180, 1159, 1133, 1076, 1038, 1003, 968, 897, 845, 765, 692; 1H NMR (300 MHz, CDCl3) δ
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13.12 (s, 1H, OH), 8.04ꢀ7.98 (m, 3H), 7.80ꢀ7.68 (m, 6H), 7.53ꢀ7.31 (m, 8H); C NMR (75
MHz, CDCl3) δ 153.1 (C), 149.8 (C), 145.9 (C), 143.9 (C), 140.0 (C), 139.7 (C), 136.8 (C),
133.5 (CH), 129.0 (2×CH), 128.9 (2×CH), 128.4 (CH), 128.0 (3×CH), 127.3 (2×CH), 127.2
(2×CH), 122.7 (2×CH), 119.0 (CH), 116.4 (CH); HRMS (TOFꢀESI) m/z: Calcd for
C24H19N2O [M + H]+ 351.1492, found 351.1471.
(E)-2-(Phenyldiazenyl)phenol (2i).16 2i was prepared following the general procedure for 5
h. Yield 81% (32 mg); orange solid, mp 81ꢀ82 °C; IR (neat, cmꢀ1) 3057, 2924, 2852, 1617,
1594, 1487, 1454, 1416, 1365, 1321, 1273, 1214, 1182, 1144, 1113, 1069, 1030, 1017, 940,
916, 853, 814, 770, 753, 680; 1H NMR (300 MHz, CDCl3) δ 12.94 (s, 1H, OH), 7.96 (dd, J =
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7.8 Hz, J = 1.6 Hz, 1H), 7.88 (m, 2H), 7.51 (m, 3H), 7.36 (m, 1H), 7.07 (m, 2H); C NMR
(75 MHz, CDCl3) δ 152.9 (C), 150.6 (C), 137.5 (C), 133.4 (2×CH), 131.3 (CH), 129.5
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(2×CH), 122.4 (2×CH), 120.1 (CH), 118.3 (CH); HRMS (TOFꢀESI) m/z: Calcd for
C12H11N2O [M + H]+ 199.0866, found 199.0878.
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(E)-2-Fluoro-6-[(3-fluorophenyl)diazenyl]phenol and (E)-4-fluoro-2-[(3-fluorophenyl)
diazenyl]phenol (2j). 2j was prepared following the general procedure for 4 h. Yield 60% (29
mg); orange solid; IR (neat, cmꢀ1) 3069, 1588, 1494, 1476, 1452, 1443, 1409, 1355, 1301,
1280, 1255, 1231, 1210, 1159, 1136, 1117, 1024, 981, 961, 875, 838, 786, 725, 674; 1H NMR
(300 MHz, CDCl3) δ 12.62 (s, 0.29H, OH), 12.15 (s, 0.71H, OH), 7.65 (d, J = 13.6 Hz,
0.29H), 7.63ꢀ7.39 (m, 4.42H), 7.17ꢀ7.11 (m, 1.29H), 7.08ꢀ7.02 (m, 1H), 6.95ꢀ6.90 (m, 1H);
13C NMR (75 MHz, CDCl3) δ (E)-2-fluoro-6-[(3-fluorophenyl)diazenyl]phenol 163.4 (d, JCꢀ
F = 247.1 Hz, C), 156.0 (d, JCꢀF = 240.0 Hz, C), 151.9 (d, JCꢀF = 7.2 Hz, C), 149.0 (C), 136.5
(d, JCꢀF = 8.8 Hz, C), 130.6 (d, JCꢀF = 8.3 Hz, CH), 121.0 (d, JCꢀF = 23.6 Hz, CH), 120.1 (CH),
119.0 (d, JCꢀF = 7.7 Hz, CH), 118.4 (d, JCꢀF = 21.9 Hz, CH), 117.8 (d, JCꢀF = 23.5 Hz, CH),
107.6 (d, JCꢀF = 23.4 Hz, CH); 19Fꢀdecoupling NMR (188 MHz, CDCl3) δ (E)-2-fluoro-6-[(3-
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fluorophenyl)diazenyl]phenol
ꢀ111.41,
ꢀ124.39,
(E)-4-fluoro-2-[(3-fluorophenyl)
diazenyl]phenol ꢀ111.33, ꢀ137.56; HRMS (TOFꢀESI) m/z: Calcd for C12H7N2OF2 [M − H]−
233.0532, found 233.0519.
(E)-4-Chloro-2-[(3-chlorophenyl)diazenyl]phenol and (E)-2-chloro-6-[(3-chlorophenyl)
diazenyl]phenol (2k).28 2k was prepared following the general procedure for 3 h. Yield 69%
(37 mg); orange solid; IR (neat, cmꢀ1) 3063, 2924, 2852, 1606, 1586, 1485, 1401, 1343, 1285,
1267, 1223, 1209, 1164, 1140, 1096, 1084, 1017, 905, 883, 823, 801, 789, 731, 674; 1H NMR
(300 MHz, CDCl3) δ 13.37 (s, 0.23H, OH), 12.42 (s, 0.77H, OH), 7.93 (d, J = 2.1 Hz, 0.77H),
7.86 (m, 1.46H), 7.75 (m, 1.23H), 7.46 (m, 2.54H), 7.31 (dd, J = 9.0 Hz, J = 2.3 Hz, 0.77H),
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7.26 (m, 0.23H), 7.05 (m, 0.23H), 6.98 (d, J = 8.9H, 0.77H); C NMR (75 MHz, CDCl3) δ
151.4 (2×C), 151.3 (C), 150.9 (C), 149.2 (C), 137.7 (C), 137.3 (C), 135.8 (C), 135.7 (C),
133.9 (CH), 133.7 (CH), 132.3 (CH), 132.2 (CH), 131.6 (CH), 131.6 (CH), 130.6 (CH), 130.6
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(CH), 124.8 (C), 122.3 (CH), 120.0 (CH), 121.5 (CH), 121.2 (CH), 120.1 (CH), 119.8 (CH);
HRMS (TOFꢀESI) m/z: Calcd for C12H9N2OCl2 [M + H]+ 267.0086, found 267.0096.
(E)-4-Methoxy-2-[(3-methoxyphenyl)diazenyl]phenol (2l). 2l was prepared following the
general procedure using 1.2 eq of PIFA for 5 h. Yield 35% (18 mg); orange solid, mp 75ꢀ78
°C; IR (neat, cmꢀ1) 2962, 2833, 1605, 1581, 1481, 1433, 1344, 1317, 1288, 1260, 1194, 1130,
1095, 1079, 1039, 1010, 893, 869, 799, 781, 726, 681; 1H NMR (300 MHz, C6D6) δ 12.73 (s,
1H, OH), 7.49 (d, J = 3.1 Hz, 1H), 7.39 (t, J = 2.0 Hz, 1H), 7.26 (m, 1H), 7.03ꢀ6.96 (m, 2H),
6.81ꢀ6.77 (m, 2H), 3.31 (s, 3H), 3.24 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 160.5 (C), 152.9
(C), 151.8 (C), 147.3 (C), 136.9 (C), 130.0 (CH), 121.7 (CH), 118.8 (CH), 117.9 (CH), 116.5
(CH), 114.7 (CH), 105.0 (CH), 55.9 (CH3), 55.5 (CH3); HRMS (TOFꢀESI) m/z: Calcd for
C14H15N2O3 [M + H]+ 259.1077, found 259.1081.
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(E)-2,4-Dichloro-6-[(3,5-dichlorophenyl)diazenyl]phenol (2m). 2m was prepared
following the general procedure using 7.5 mol% of Pd(OAc)2 for 40 h. Yield 45% (30 mg);
orange solid, mp 150ꢀ152 °C; IR (neat, cmꢀ1) 3078, 2963, 1759, 1566, 1470, 1434, 1400,
1337, 1281, 1238, 1216, 1166, 1093, 1016, 944, 865, 803, 854, 739, 669; 1H NMR (300 MHz,
13
CDCl3) δ 12.82 (s, 1H, OH), 7.91 (d, J = 2.0 Hz, 1H), 7.78 (m, 2H), 7.52 (m, 2H); C NMR
(75 MHz, CDCl3) δ 151.2 (C), 147.8 (C), 137.1 (C), 136.2 (2×C), 133.7 (CH), 131.5 (CH),
131.0 (CH), 124.8 (C), 123.5 (C), 121.1 (2×CH); HRMS (TOFꢀESI) m/z: Calcd for
C12H5N2OCl4 [M − H]− 334.9132, found 334.9125.
(E)-3-Chloro-2-[(2-chloro-4-methylphenyl)diazenyl]-5-methylphenol (2n). 2n was
prepared following the general procedure using 7.5 mol% of Pd(OAc)2 for 48 h. Yield 42%
(25 mg); orange solid, mp 184ꢀ186 °C; IR (neat, cmꢀ1) 2962, 2921, 1597, 1558, 1451, 1402,
1295, 1259, 1190, 1096, 1053, 1014, 870, 831, 820, 783, 684; 1H NMR (300 MHz, CDCl3) δ
13.72 (s, 1H, OH), 7.92 (d, J = 8.5 Hz, 1H), 7.41 (d, J = 1.5 Hz, 1H), 7.21 (dd, J = 8.5 Hz, J =
1.5 Hz, 1H), 6.97 (d, J = 1.8 Hz, 1H), 6.78 (d, J = 1.8 Hz, 1H), 2.44 (s, 3H), 2.38 (s, 3H); 13C
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NMR (75 MHz, CDCl3) δ 154.4 (C), 145.7 (C), 144.5 (C), 143.2 (C), 137.5 (C), 133.9 (C),
132.4 (C), 130.7 (CH), 128.6 (CH), 122.4 (CH), 117.7 (CH), 117.6 (CH), 21.9 (CH3), 21.4
(CH3); HRMS (TOFꢀESI) m/z: Calcd for C14H13N2OCl2 [M + H]+ 295.0399, found 295.0394.
(E)-3-Chloro-2-[(2-chlorophenyl)diazenyl]phenol (2o). 2o was prepared following the
general procedure for 36 h. Yield 34% (18 mg); orange solid, mp 84ꢀ85 °C; IR (neat, cmꢀ1)
3066, 2968, 1699, 1583, 1565, 1464, 1445, 1433, 1406, 1329, 1280, 1258, 1231, 1180, 1154,
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1057, 1031, 953, 887, 786, 758, 707, 684; H NMR (300 MHz, CDCl3) δ 13.60 (s, 1H, OH),
8.02 (dd, J = 7.2 Hz, J = 2.5 Hz, 1H), 7.59 (dd, J = 7.2 Hz, J = 2.2 Hz, 1H), 7.46ꢀ7.42 (m,
2H), 7.31 (t, J = 8.2 Hz, 1H), 7.15 (dd, J = 7.9 Hz, J = 1.1 Hz, 1H), 7.00 (dd, J = 8.4 Hz, J =
1.1 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 154.4 (2×C), 146.5 (C), 138.2 (C), 134.4 (C),
134.2 (CH), 132.4 (CH), 130.5 (CH), 127.7 (CH), 121.3 (CH), 118.0 (CH), 117.7 (CH);
HRMS (TOFꢀESI) m/z: Calcd for C12H9N2OCl2 [M + H]+ 267.0086, found 267.0096.
(E)-2-[(2-Chlorophenyl)diazenyl]phenol
(2p)
and
(E)-3-chloro-2-
(phenyldiazenyl)phenol (2'p). 2p and 2'p were prepared following the general procedure for
48 h. Yield 54% (25 mg); orange solid; IR (neat, cmꢀ1) 3072, 2963, 2925, 1611, 1585, 1564,
1484, 1463, 1445, 1409, 1352, 1278, 1259, 1180, 1145, 1113, 1056, 1030, 950, 887, 785, 761,
684; 1H NMR (300 MHz, CDCl3) δ 13.63 (s, 0.40H, OH), 13.00 (s, 0.60H, OH), 7.99 (dd, J =
8.2 Hz, J = 1.6 Hz, 0.8H), 7.96ꢀ7.93 (m, 1.20H), 7.61ꢀ7.53 (m, 2H), 7.44ꢀ7.38 (m, 1.60H),
7.28 (m, J = 7.9 Hz, 0.4H), 7.15ꢀ7.08 (m, 1.60H), 6.96 (dd, J = 8.3 Hz, J = 1.2 Hz, 0.40H);
13C NMR (75 MHz, CDCl3) δ 154.5 (2×C), 152.7 (2×C), 150.5 (C), 146.4 (C), 138.0 (C),
137.9 (C), 133.9 (CH), 133.7 (CH), 133.6 (CH), 131.9 (CH), 131.7 (CH), 130.5 (CH), 129.5
(2×CH), 127.6 (CH), 122.7 (2×CH), 121.3 (CH), 120.0 (CH), 118.5 (CH), 117.4 (CH), 117.3
(CH); HRMS (TOFꢀESI) m/z: Calcd for C12H10N2OCl [M + H]+ 233.0476, found 233.0488.
(E)-2-[(2-Fluorophenyl)diazenyl]phenol
(2q)
and
(E)-3-fluoro-2-
(phenyldiazenyl)phenol (2'q). 2q and 2'q were prepared following the general procedure for
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20 h. Yield 65% (28 mg); orange solid; IR (neat, cmꢀ1) 3068, 2959, 2926, 1729, 1625, 1612,
1586, 1483, 1412, 1358, 1282, 1239, 1206, 1178, 1146, 1100, 1041, 1026, 816, 761, 741, 686;
1H NMR (300 MHz, CDCl3) δ 13.31 (s, 0.22H, OH), 12.84 (s, 0.78H, OH), 7.98 (dd, J = 7.9
Hz, J = 1.4 Hz, 0.78H), 7.92 (d, J = 7.7 Hz, 0.78H), 7.89 (d, J = 1.4 Hz, 0.22H), 7.54 (d, J =
7.3 Hz, 0.78H), 7.49ꢀ7.46 (m, 0.78H), 7.43 (dd, J = 7.7 Hz, J = 1.6 Hz, 0.22H), 7.39ꢀ7.37 (m,
0.78H), 7.32ꢀ7.26 (m, 1.56H), 7.26ꢀ7.24 (m, 0.44H), 7.13ꢀ7.09 (m, 0.78H), 7.07 (m, 0.44H),
6.84ꢀ6.81 (m, 0.22H), 6.79ꢀ6.76 (m, 0.22H); 13C NMR (75 MHz, CDCl3) δ (E)-2-[(2-
Fluorophenyl)diazenyl]phenol 159.2 (d, JCꢀF = 255.8 Hz, C), 154.1(C), 152.8 (C), 138.0 (C),
133.7 (CH), 133.8 (CH), 132.6 (d, JCꢀF = 8.2 Hz, CH), 124.6 (d, JCꢀF = 3.5 Hz, CH), 119.9
(CH), 118.5 (CH), 117.2 (CH), 117.0 (d, JCꢀF = 19.3 Hz, CH), (E)-3-fluoro-2-
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(phenyldiazenyl)phenol 161.6 (d, JCꢀF = 258.2 Hz, C), 152.8 (C), 150.4 (C), 138.4 (d, JCꢀF
=
6.9 Hz, C), 134.1 (d, JCꢀF = 11.0 Hz, CH), 131.6 (CH), 129.4 (2×CH), 122.5 (2×CH), 113.8
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(d, JCꢀF = 3.4 Hz, CH), 106.5 (d, JCꢀF = 19.8 Hz, CH); F NMR (188 MHz, CDCl3) δ (E)-2-
[(2-fluorophenyl)diazenyl]phenol (2q) ꢀ122.65; (E)-3-fluoro-2-(phenyldiazenyl)phenol
(2'q) ꢀ118.95; HRMS (TOFꢀESI) m/z: Calcd for C12H10N2OF [M + H]+ 217.0772, found
217.0780.
(E)-2-[(4-Bromo-2-chlorophenyl)diazenyl]phenol (2r). 2r was prepared following the
general procedure for 48 h. Yield 45% (28 mg); orange solid, mp 114ꢀ116 °C; IR (neat, cmꢀ1)
3082, 2962, 2924, 1612, 1582, 1476, 1454, 1409, 1343, 1274, 1226, 1208, 1179, 1143, 1081,
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1054, 1028, 945, 867, 818, 793, 737, 702, 660; H NMR (300 MHz, CDCl3) δ 12.81 (s, 1H,
OH), 7.96 (dd, J = 7.8 Hz, J = 1.6 Hz, 1H), 7.80 (d, J = 8.7 Hz, 1H), 7.76 (d, J = 2.0 Hz, 1H),
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7.52 (dd, J = 8.7 Hz, J = 2.0 Hz, 1H), 7.44ꢀ7.39 (m, 1H), 7.13ꢀ7.06 (m, 2H); C NMR (75
MHz, CDCl3) δ 152.7 (C), 145.5 (C), 137.9 (C), 134.8 (C), 134.3 (CH), 133.8 (CH), 133.1
(CH), 131.0 (CH), 125.4 (C), 120.1 (CH), 118.6 (CH), 118.3 (CH); HRMS (TOFꢀESI) m/z:
Calcd for C12H9N2OClBr [M + H]+ 312.9575, found 312.9580.
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(E)-2-[(4-Methoxyphenyl)diazenyl]phenol (2s) and (E)-5-methoxy-2-(phenyldiazenyl)
phenol (2's) . 2s and 2's were prepared following the general procedure for 4 h. Yield 26%
(12 mg); orange solid; IR (neat, cmꢀ1) 3079, 2967, 2838, 1601, 1580, 1502, 1455, 1434, 1392,
1371, 1315, 1277, 1205, 1185, 1150, 1102, 1028, 965, 832, 796, 756, 719, 683; 1H NMR (300
MHz, CDCl3) δ 13.89 (s, 0.30H, OH), 12.92 (s, 0.70H, OH), 7.96ꢀ7.93 (m, 0.60H), 7.88 (d, J
= 9.0 Hz, 1.40H), 7.84ꢀ7.78 (m, 1H), 7.54ꢀ7.49 (m, 1.30H), 7.46 (d, J = 7.1 Hz, 0.30H), 7.33
(td, J = 8.1 Hz, J = 1.7 Hz, 0.70H), 7.10ꢀ7.07 (m, 0.70H), 7.04 (d, J = 9.0 Hz, 1.40H), 6.63
(dd, J = 8.9 Hz, J = 2.6 Hz, 0.30H), 6.48 (d, J = 2.6 Hz, 0.30H), 3.91 (s, 2.10H, CH3), 3.89 (s,
0.90H, CH3) ; 13C NMR (75 MHz, CDCl3) δ 164.1 (C), 162.2 (C), 156.9 (C), 152.7 (C), 150.0
(C), 144.7 (C), 137.3 (C), 134.7 (CH), 132.9 (C), 132.6 (CH), 132.4 (2×CH), 130.0 (CH),
129.3 (2×CH), 124.0 (2×CH), 121.5 (CH), 119.8 (CH), 118.0 (CH), 114.6 (2×CH), 108.4
(CH), 101.4 (CH), 55.7 (CH3), 55.6 (CH3); (HRMS (TOFꢀESI) m/z: Calcd for C13H13N2O2 [M
+ H]+ 229.0972, found 229.0970.
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Ethyl (E)-4-[(2-hydroxyphenyl)diazenyl]benzoate (2t) and ethyl (E)-3-hydroxy-4-
phenyl diazenyl benzoate (2't). 2t and 2't were prepared following the general procedure for
10 h. Yield 65% (35 mg); orange solid; IR (neat, cmꢀ1) 2962, 1720, 1589, 1486, 1467, 1449,
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1426, 1405, 1361, 1316, 1283, 1259, 1146, 1123, 1022, 964, 842, 798, 771, 753, 685; H
NMR (300 MHz, CDCl3) δ 12.79 (s, 1H, OH), 8.21 (d, J = 8.5 Hz, 1.33H), 8.02 (m, 0.33H),
7.99 (d, J = 7.9 Hz, 0.67H), 7.92 (d, J = 8.5 Hz, 1.33H), 7.74 (m, 0.67H), 7.55 (m, 1H), 7.40
(m, 1H), 7.09 (m, 1.67H), 4.41 (m, 2H, CH2), 1.45 (t, J = 7.2 Hz, 2.01H), 1.44 (t, J = 6.8 Hz,
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0.99H); C NMR (75 MHz, CDCl3) δ 165.8 (C), 165.6 (C), 153.1 (C), 152.9 (C), 152.2 (C),
150.5 (C), 147.2 (C), 139.2 (C), 137.6 (C), 134.1 (CH), 133.7 (CH), 132.9 (CH), 132.3 (C),
131.9 (CH), 130.8 (2×CH), 129.5 (2×CH), 122.6 (2×CH), 122.0 (2×CH), 120.7 (CH), 120.1
(CH), 119.8 (CH), 118.4 (CH), 61.4 (CH2), 61.3 (CH2), 14.6 (2×CH3); HRMS (TOFꢀESI)
m/z: Calcd for C15H15N2O3 [M + H]+ 271.1077, found 271.1072.
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(E)-2-[(4-Bromophenyl)diazenyl]phenol
(2u)
and
(E)-5-bromo-2-
4
5
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7
8
(phenyldiazenyl)phenol (2'u). 2u and 2'u were prepared following the general procedure for
4 h. Yield 70% (38 mg); orange solid; IR (neat, cmꢀ1) 3081, 2965, 1608, 1584, 1478, 1419,
1395, 1342, 1269, 1174, 1142, 1065, 1028, 1004, 939, 917, 882, 853, 751, 684; 1H NMR (300
MHz, CDCl3) δ 13.11 (s, 0.16H, OH), 12.70 (s, 0.84H, OH), 7.95 (dd, J = 7.9 Hz, J = 1.5 Hz,
0.84H), 7.87 (dd, J = 8.0 Hz, J = 2.5 Hz, 0.32H), 7.77 (d, J = 8.6 Hz, 1.68H), 7.67 (d, J = 8.6
Hz, 1.68H), 7.55ꢀ7.24 (m, 0.48H), 7.42ꢀ7.36 (m, 0.84H), 7.28 (s, 0.16H), 7.24 (m, 0.32H),
7.12ꢀ7.04 (m, 1.68H); 13C NMR (75 MHz, CDCl3) δ (E)-2-[(4-bromophenyl)diazenyl]
phenol 152.8 (C), 149.4 (C), 137.4 (C), 133.7 (CH), 133.3 (CH), 132.6 (2×CH), 125.5 (C),
123.6 (2×CH), 120.1 (CH), 118.3 (CH); HRMS (TOFꢀESI) m/z: Calcd for C12H10N2OBr [M +
H]+ 276.9971, found 276.9986.
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(E)-2-[(4-Fluorophenyl)diazenyl]phenol
(2v)
and
(E)-5-fluoro-2-
(phenyldiazenyl)phenol (2'v). 2v and 2'v were prepared following the general procedure for
4 h. Yield 55% (24 mg); orange solid; IR (neat, cmꢀ1) 3061, 2961, 2853, 1611, 1594, 1580,
1499, 1481, 1430, 1403, 1345, 1319, 1260, 1234, 1176, 1093, 1028, 980, 862, 805, 753, 684;
1H NMR (300 MHz, CDCl3) δ (E)-2-[(4-Fluorophenyl)diazenyl]phenol 12.70 (s, 1H, OH),
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7.96ꢀ7.88 (m, 3H), 7.40ꢀ7.35 (m, 1H), 7.27ꢀ7.22 (m, 2H), 7.12ꢀ7.04 (m, 2H); C NMR (75
MHz, CDCl3) δ 164.4 (d, JCꢀF = 251.1 Hz, C), 152.7 (C), 147.1 (C), 137.2 (C), 133.3 (CH),
133.1 (CH), 124.2 (d, JCꢀF = 8.8 Hz, 2×CH), 120.0 (CH), 118.2 (CH), 116.3 (d, JCꢀF = 22.9 Hz,
2×CH); 19F NMR (188 MHz, CDCl3) δ (E)-2-[(4-fluorophenyl)diazenyl]phenol (2v) ꢀ
106.75, (E)-5-fluoro-2-(phenyldiazenyl)phenol (2'v) ꢀ101.95, HRMS (TOFꢀESI) m/z: Calcd
for C12H10N2OF [M + H]+ 217.0772, found 217.0777.
Ethyl (E)-3-hydroxy-4-[(4-methoxyphenyl)diazenyl]benzoate (2w) and ethyl (E)-4-[(2-
hydroxy-4-methoxyphenyl)diazenyl]benzoate (2'w). 2w and 2'w were prepared following
the general procedure for 24 h. Yield 60% (36 mg); orange solid; IR (neat, cmꢀ1) 2926, 2852,
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1704, 1627, 1600, 1501, 1466, 1418, 1365, 1271, 1249, 1104, 1094, 1024, 862, 837, 800, 691;
1H NMR (300 MHz, CDCl3) δ 14.03 (s, 0.44H, OH), 12.76 (s, 0.56H, OH), 8.17 (d, J = 8.5
Hz, 1.12H), 7.96 (dd, J = 8.3 Hz, J = 2.5 Hz, 0.56H), 7.90 (d, J = 9.0 Hz, 0.88H), 7.83 (d, J =
9.0 Hz, 0.88H), 7.78ꢀ7.70 (m, 1.56H), 7.04 (d, J = 9.0 Hz, 1.12 Hz), 6.63 (d, J = 9.2 Hz,
0.44H), 6.45 (s, 0.44H), 4.42 (m, 2H), 3.92 (s, 1.68H), 3.89 (s, 1.32H), 1.44 (t, J = 7.1 Hz,
1.68H), 1.44 (t, J = 7.1 Hz, 1.32H); 13C NMR (75 MHz, CDCl3) δ 165.9 (C), 165.7 (C), 165.1
(C), 162.9 (C), 158.8 (C), 152.3 (C), 152.1 (C), 144.6 (C), 139.2 (C), (135.1 (CH), 133.6 (C),
133.1 (C), 132.2 (CH), 130.9 (C), 130.7 (2×CH), 124.5 (2×CH), 120.9 (2×CH), 120.6 (CH),
119.6 (CH), 114.7 (2×CH), 109.6 (CH), 101.4 (CH), 61.3 (CH2), 61.2 (CH2), 55.7 (CH3), 55.6
(CH3), 14.3 (2×CH3) ; HRMS (TOFꢀESI) m/z: Calcd for C16H17N2O4 [M + H]+ 301.1183,
found 301.1196.
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Acknowledgments
The authors thank K. Leblanc for performing mass analyses. The Agence Nationale de la
Recherche (ANRꢀ13ꢀBSV8ꢀ0020), the University of ParisꢀSud, the French Ministry of
Superior Education and Research, the CNRS and the LabEx Lermit are gratefully
acknowledged for financial support.
Supporting Information
1
Full characterization details including H, 13C and 19F NMR spectra. Reaction optimization
via in situ generation of PIFA. This material is available free of charge via the Internet at
http://pubs.acs.org.
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References
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