Porphyrin Co(III)-nitrene radical mediated pathway for synthesis of o-aminoazobenzenes

Article abstract of DOI:10.3390/molecules23051052

Azobenzenes are versatile compounds with a range of applications, including dyes and pigments, food additives, indicators, radical reaction initiators, molecular switches, etc. In this context, we report a general method for synthesizing o-aminoazobenzene

Full text of DOI:10.3390/molecules23051052

molecules
Article
Porphyrin Co(III)-Nitrene Radical Mediated Pathway
for Synthesis of o-Aminoazobenzenes
ID
Monalisa Goswami and Bas de Bruin *
Homogeneous, Supramolecular and Bio-Inspired Catalysis, van ‘t Hoff Institute for Molecular Sciences,
University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands; m.goswami@uva.nl
* Correspondence: B.deBruin@uva.nl; Tel.: +31-20-525-6495
Academic Editor: John C. Walton
Received: 3 April 2018; Accepted: 26 April 2018; Published: 1 May 2018
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Abstract: Azobenzenes are versatile compounds with a range of applications, including dyes and
pigments, food additives, indicators, radical reaction initiators, molecular switches, etc. In this
context, we report a general method for synthesizing o-aminoazobenzenes using the commercially
available cobalt(II) tetraphenyl porphyrin [CoII(TPP)]. The net reaction is a formal dimerization of
two phenyl azides with concomitant loss of two molecules of dinitrogen. The most commonly used
methodology to synthesize azobenzenes is based on the initial diazotization of an aromatic primary
amine at low temperatures, which then reacts with an electron rich aromatic nucleophile. As such,
this limits the synthesis of azobenzenes with an amine functionality. In contrast, the method we
report here relies heavily on the o-amine moiety and retains it in the product. The reaction is metal
catalyzed and proceeds through a porphyrin Co(III)-nitrene radical intermediate, which is known to
form on activation of organic azides at the cobalt center. The synthesized o-aminoazobenzenes are
bathochromatically shifted, as compared to azobenzenes without amine substituents. Based on the
crystal structure of one of the products, strong H-bonding between the N-atom of the azo functionality
and the H of the NH2 substituent is shown to stabilize the trans isomeric form of the product. The NH2
substituents offers possibilities for further functionalization of the synthesized azo compounds.
Keywords: azides; azobenzenes; nitrene radicals; base-metals; dyes; molecular switches
1. Introduction
Azobenzenes are versatile compounds with a range of applications, including dyes and pigments,
food additives, indicators, radical reaction initiators, and therapeutic agents [1–10]. In addition,
azo compounds have shown promise in electronics and drug delivery [11]. They have also been
proposed to be useful for applications in areas of nonlinear optics, chemosensors, liquid crystals,
photochemical molecular switches, molecular shuttles, nanotubes, and in the manufacture of protective
eye-glasses and filters [1–10]. To fully exploit the potential of these molecules for such versatile
applications, it is important that they be easy to synthesize. A review on the synthesis of azobenzenes by
Merino in 2011 summarizes all of the commonly employed methods for synthesizing azobenzenes [11].
The most commonly used method is based on the initial diazotization of an aromatic primary amine at
low temperature, which then reacts with an electron rich aromatic nucleophile. As such, this limits the
synthesis of azobenzenes, which have an amine functionality.
Ring substituents lead to drastic changes in the absorption, emission and photochemical
properties of azobenzene [12]. Most of the azobenzene-modified biomolecules developed so far
can undergo photoisomerization upon irradiation with UV light [13]. Azobenzene derivatives for
which photoisomerization can occur entirely in the visible region are desirable for in vivo applications.
A handful of examples exist in which introduction of suitable substituents makes the switching of these
Molecules 2018, 23, 1052; doi:10.3390/molecules23051052
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molecules possible at longer wavelengths, thereby obviating the need to use UV irradiation [14–16].
Therefore, catalytic methods, with functional group tolerance, for the synthesis of amine containing
azo-compounds will aid in the further development of this field.
To date, only a few examples of catalytic synthesis of azobenzenes via azides have been reported.
These are summarized in Scheme 1. The iron-based example of Groysman and co-workers is limited
in the sense that only azides with bulky substitutents like mesityl groups result in formation of azo
compounds [17]. With trifluoromethyl and methyl substituents, dimers of the metal complex are
obtained. The other example from Cundari and co-workers [18] involves a nickel complex, but this
system produces only stoichiometric amounts of azo compounds. An example involving a ruthenium
metallo-radical system proceeds via a free nitrene intermediate and works catalytically only for aryl
azides with electron-rich substituents such as OMe and OEt [19]. Very recently, another dinuclear nickel
complex was reported to be effective in the homo- and hetero-coupling of azides, giving azoarenes by
means of the concomitant release of dinitrogen. The mononuclear version of the same complex did not
lead to catalytic turnover [20].
Scheme 1. Summary of reported transition metal complexes for synthesis of azobenzenes and the
catalytic reaction reported in this work.
As part of our previous publication in 2016, we reported a unique reaction that led to the synthesis
of the simple o-aminoazobenzene in high yield using a cobalt(II) porphyrin catalyst [21]. In this regard,
we now report a general catalytic synthesis of substituted o-aminoazobenzenes in two steps starting
from commercially available substituted anilines. In this method, the anilines are first o-azidated
using a reported Cu-catalyzed route [22]; then, in the unique cobalt(II) porphyrin-catalyzed pathway,
the azides are activated by cobalt, leading to net ‘nitrene dimerization’, giving the azobenzenes.
Cobalt(II) porphyrins have emerged as a new class of catalysts that can perform carbene and nitrene
transfer reactions via discreet Co(III)-carbene or nitrene radicals [23–26]. The advantage of these
cobalt(II) porphyrins lies in the fact that they can activate organic azides, thus obviating the need to
use hypervalent iodine compounds like iminoiodanes or Halomine-Ts. Thus, cobalt(II) porphyrins
are excellent catalysts for cleaner and milder access to nitrene transfer reactions. The utility of
the method we report here is two-fold. Firstly, this catalytic method allows for a mild chemical
method that is tolerant to primary amines to access azobenzenes via azides. The only by-product
in this key step is dinitrogen. The only other way to access azobenzenes from organic azides is by
uncatalyzed thermolysis, and the explosive nature of the azides is often pointed out as a disadvantage

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of using azides in such high-temperature uncatalyzed processes. Secondly, as ortho substituents are
known to have dramatic effects in the photochemical properties of azobenzenes, this method gives
access to a series of o-amino-substituted azobenzenes that have thus far not been extensively studied.
The primary amine substituent can provide an easy handle for further functionalization. This presents
new possibilities for the use of azobenzenes in a variety of applications including optical switches.
Overall this method allows for synthesis of new azobenzenes starting from commercially available
anilines in good to excellent isolated yields.
2. Results
As a test substrate
described by Jiao and co-workers [22].
1 (2-azido-6-(tert-butyl)aniline) was synthesized according to the method
1
(0.3 mmol) and [CoII(TPP)] (5 mol%) were dissolved in
◦
freshly distilled toluene and the reaction mixture was heated at 90 C for 18 h (Scheme 2). During this
time, the reaction proceeded cleanly, giving the corresponding azobenzene in near quantitative yield.
The product was isolated by running a preparatory thin layer chromatography (prep-TLC) in pure
dichloromethane (DCM). The isolated compound was a deep red-colored solid and was crystallized to
confirm the formation of the o-aminoazobenzene product.
Scheme 2. Left: [CoII(TPP)] catalyzed reaction of 2-azido-6-(tert-butyl)aniline, giving the corresponding
trans-azobenzene. Right: Crystal structure of the thus-formed o-aminoazobenzene product.
With these results in hand, we set out to optimize this reaction further. Unfortunately, lowering
the catalyst loading and/or temperature was detrimental to the reaction. These results are summarized
in Table 1. The reaction temperature plays a very important role in this reaction. With 1 mol%
catalyst loading in toluene at 90 ◦C the reaction proceeded, but the yields dropped (entry 4).
Lower temperatures didn’t lead to any azobenzene formation in benzene or in THF (entries 2 and 5).
Without catalyst present, the azide was unreacted and could be fully recovered from the reaction
mixture (entry 6).
Table 1. Optimization of [CoII(TPP)]-catalyzed synthesis of azobenzene from azide
1 as a test substrate *.
◦
Entry
Solvent
Temperature ( C)
Catalyst Loading
Yield
1
2
3
4
5
6
Toluene
Benzene
Toluene
Toluene
THF
90
60
60
90
60
90
5 mol%
5 mol%
5 mol%
1 mol%
5 mol%
98%
-
-
60%
-
-
Toluene
No catalyst
* All reactions were carried out with 0.3 mmol of azide, [CoII(TPP)] in 4 mL of toluene. The reaction mixtures were
bubbled with dinitrogen for 15 min prior to thermostatting at the stated temperature for 18 h.
Using the optimized reaction conditions as determined above, we proceeded towards synthesizing
various other substituted o-azidoanilines. The results are summarized in Figure 1. Substrates with
electron-donating substituents performed better in this reaction than those with electron-withdrawing
groups. For example, the phenyl substitution in
E gave 60% of the product, while bromine substitution

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in
(and a MeO substituent) or substrate
were formed, and in some cases (entries
azides, the cobalt is not able to activate the azides to give the crucial nitrene-radical intermediate.
F
gave a 48% yield. Furthermore, in catalytic reactions using substrate
I
containing a CF3 substituent
J
containing a fluorine substituent, no azobenzene products
and ) starting azide was recovered. Apparently, with these
I
J
Substrates containing tert-butyl (C) or iso-propyl (D) groups gave excellent yields (see Supporting
Information for spectra).
Figure 1. Substrate screening for [CoII(TPP)] catalyzed synthesis of azobenzenes from o-amine
substituted azides *. * All reactions were carried out with 0.3 mmol of azide, [CoII(TPP)] (5 mol%) in
4 mL of toluene. The reaction mixtures were bubbled with dinitrogen for 15 min prior to thermostatting
at the stated temperature for 18 h. Isolated yields are reported.
As reported previously by us, the reaction is believed to proceed via the mechanism outlined in
Scheme 3 [21]. The formation of azobenzene from ortho-amino phenyl azides is proposed to proceed via
the phenylene diimine (OPDI) intermediate can be reasoned in the mechanism depicted in Scheme 3.
Upon activation of the azide by the cobalt(II) porphyrin, a nitrene radical intermediate
C
is formed.
Such nitrene radical intermediates have previously been fully characterized by us [25
,
26]. In the
presence of an ortho-NH2 substituent, this nitrene radical intermediate undergoes an intramolecular
H-atom abstraction from the amine substituent. This leads to formation of an OPDI intermediate,
which couples to another OPDI molecule. Rearrangement of a proton then leads to the formation of
the azobenzene product, as depicted in Scheme 3. The barrier for the intramolecular HAT step in going
from
C to D
was previously reported by us and was found to be only +9.1 kcal mol−1; the overall
process was exergonic by −3.1 kcal mol−1
.

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Scheme 3. Proposed mechanism of the Co(II) porphyrin-catalyzed route to o-amino-azobenzenes via
o-amino-azides.
3. Electronic Properties of the Synthesized o-Amino-Substituted-Azobenzenes
In addition to the synthesis, we also recorded the UV-vis spectra of the synthesized
o-aminoazobenzenes to see what effect the amine substituent has on the absorption spectra.
As expected, all the synthesized compound products showed a red shift of the
in comparison to the parent azobenzene compound. Three such UV-vis spectra with electronically
different substituents are shown in Figure 2 (left). The n- * transitions are shifted to wavelengths
above 450 nm, and * transitions between 300 and 350 nm are of almost equal intensity to the
n- * transitions. For azobenzenes with electron-donating substituents, the * transition is more
π-π* and n-π* transitions
π
π-π
π
π-π
red-shifted than for those with electron-withdrawing substituents (Figure 2, left). Time-dependent DFT
(TD DFT) calculation reasonably reproduced these experimentally observed transitions and relative
intensities. For example, for the bromo-substituted compound
almost exactly ( = 323 nm), while the n- * transition was more red shifted in reality than was predicted
by the TD DFT calculations (λ = 430 nm (TD DFT) and 463 nm (experimental)).
F the π-π* transition value matched
λ
π

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0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
Br
NH2
0.6
0.4
0.2
0.0
N
N
R
H2N
H2N
N
N
NH2
Br
R
TD DFT calculated
Experimental
R= i-Pr, Br, Ph
250 300 350 400 450 500 550 600 650 700 750 800
Wavelength
400
600
Wavelength
Figure 2. UV-vis spectra of o-aminoazobenzenes
D
(R = i-Pr),
E
(R = Ph) and F (R = Br) with varying
electronic substituents in solvent acetonitrile (left). TD-DFT calculated (blue) and experimental UV-vis
spectra (red) of compound F (right).
H-bonding between the H atom of the NH2 and the N atom of the azo group was evident
from the crystal structure of compound
C
. The NH· · · N=N hydrogen bond was found to be 2.219 Å.
Such H-bonding interactions are known to hinder the isomerization pathway between the trans- and the
cis- isomers of amino-azobenzenes (Figure 3). Additionally, in 2-hydroxy-azobenzenes, intramolecular
H-bonding between the azo-nitrogen atom and the hydroxyl group is reported to lock the molecule in
the trans conformation [27]. The 2-hydroxyazobenzenes provide a versatile platform for the design
of reversible photoacids to generate significant pH pulses and oscillations with monochromatic light.
Similar behavior can perhaps be expected for the ortho-amino-azobenzenes reported here, but this is
beyond the scope of the current study.
Figure 3. The NH· · · N=N hydrogen bonds in
C as revealed by X-ray diffraction studies
(CCDC 1828796).
4. Materials and Methods
All NMR spectra were recorded at 293 K. 1H-NMR: Bruker Avance 400 (400 MHz) (Rheinstetten,
Germany or Varian Mercury 300 (300 MHz) (Palo Alto, California) was used, referenced internally
to residual solvent resonance of CDCl3 (δ = 7.26 ppm). 13C{1H} NMR: Bruker Avance 400 (101 MHz)
or Bruker Avance 500 (126 MHz), referenced internally to residual solvent resonance of CDCl3
(δ = 77.2 ppm). High-Resolution Mass spectra were measured on an AccuTOF LC, JMS-T100LP
Mass spectrometer (JEOL, Tokyo, Japan), Needle voltage 2000 V, Orifice 1 voltage 90 V, Orifice 2

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voltage 9 V, Ring Lens voltage 22 V. Ion source temperature 30 ◦C, solution flow rate 0.01 mL/min.
All mass spectra were recorded with an average duration of 1 min. All chemicals were purchased
from commercial sources unless otherwise mentioned. Solvents for all catalytic reactions were freshly
distilled from sodium for toluene and for acetonitrile over calcium hydride. Reactions were performed
using standard Schlenk techniques under an atmosphere of dinitrogen.
4.1. Synthesis of the Azides
Caution: All azides were synthesized in 1 mmol scale reactions in separate Schlenk tubes. After the
reactions were complete, they were combined together before work-up and column separation.
2-azido-6-(tert-butyl)aniline. 2-azido-6-(tert-butyl)aniline was synthesized according to the reported
procedure of Jiao [22] and the spectral data matched with those reported [22].
2-azido-6-iso-propylaniline. 1 mmol of isopropylaniline was added to a flame-dried Schlenk tube
containing 0.1 mmol CuBr. Then trimethyl silyl azide (2 mmol) was added, followed by addition of
4 mL of freshly distilled acetonitrile. Finally, 2 mmol of tetrabutyl h◦ydroperoxide (TBHP) (5.0–6.0 M
in decane) was added, and the reaction was thermostatted at 30 C for 6 h. After this, 15 mL of
ethyl acetate was added the reaction mixture concentrated on a rotary evaporator. This was then
1
directly loaded onto a silica column and eluted with pet ether:ethylacetate (60:1). H-NMR (400 MHz,
Chloroform-d):
δ 7.04–6.87 (m, 2H), 6.81 (t, J = 7.8 Hz, 1H), 3.84 (s, 3H), 2.98–2.66 (m, 1H), 1.25 (d,
J = 6.8 Hz, 6H). IR: 2110 cm−1 azide stretch. 13C-NMR (75 MHz, CDCl3):
δ 135.71, 134.34, 125.79,
122.40, 119.26, 116.19, 28.42, 22.69. HRMS calcld 176.1062, found 176.1058.
2-azido-6-methylaniline. 1 mmol of o-toluidine was added to a flame-dried Schlenk tube containing
0.10 mmol of CuBr. Then, trimethyl silyl azide (2 mmol) was added, followed by addition of 4 mL of
freshly distilled acetonitrile. Finally, 2 mmol of TBHP (5.0–6.0 M in decane) was added, and the reaction
◦
was thermostatted at 30 C for 6 h. After this, 15 mL of ethyl acetate was added, and the reaction
mixture was concentrated on a rotary evaporator. This was then directly loaded onto a silica column
1
and eluted with pet ether: ethylacetate (60:1). H-NMR (300 MHz, Chloroform-d):
δ 6.94 (d, J = 7.9 Hz,
1H), 6.87 (d, J = 7.4 Hz, 1H), 6.73 (t, J = 7.7 Hz, 1H), 3.77 (s, 2H), 2.17 (s, 3H). IR: 2113 cm−1 azide
stretch. 13C-NMR (75 MHz, CDCl3):
148.0749, 148.0746.
δ 136.31, 126.74, 124.83, 123.46, 118.36, 115.96, 17.35. HRMS calcld
2-azido-6-bromoaniline. 2-Bromoaniline (1 mmol) was added to a flame-dried Schlenk tube containing
0.10 mmol of CuBr. Then, TMSN3 (2 mmol) was added, followed by addition of 4 mL of freshly distilled

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acetonitrile. Finally, 2 mmol of TBHP (5.0–6.0 M in decane) was added, and the reaction was heated
to 30 ◦C for 6 h. Then, 15 mL of ethyl acetate was added, and the reaction mixture was evaporated.
It was then directly loaded onto silica (hexane: ethylacetate (90:10)) to give the desired product in 23%
1
isolated yield. H-NMR (400 MHz, Chloroform-d):
δ 7.21 (dd, J = 8.0, 1.3 Hz, 1H), 6.98 (dd, J = 7.9,
1.3 Hz, 1H), 6.65 (t, J = 8.0 Hz, 1H), 4.25 (s, 2H). IR: 2117 cm−1 azide stretch. 13C-NMR (101 MHz,
Chloroform-d): δ 136.51, 128.72, 125.97, 118.89, 117.31, 109.55. HRMS calcld 211.9697, found 211.9684.
2-azido-3,5-dimethylaniline. 2,4 dimethyl aniline (1 mmol) was added to a flame-dried Schlenk tube
contianing 0.1 mmol of CuBr. Then, TMSN3 (2 mmol) was added, followed by addition of 4 mL
of freshly distilled acetonitrile. Finally, 2 mmol of TBHP (5.0–6.0 M in decane) was added, and the
◦
reaction was heated to 30 C for 6 h. Then, 15 mL of ethyl acetate was added, and the reaction mixture
was evaporated. It was then directly loaded on silica (Pet ether: EtOAc (60:1)) to give the desired
product in 60% isolated yield. Analytical data matched literature [22].
2-azido-3,6-dimethylaniline. 2,6-dimethyl aniline (1 mmol) was added to a flame-dried Schlenk tube
containing 0.1 mmol of CuBr. Then, TMSN3 (2 mmol) was added, followed by addition of 4 mL
of freshly distilled acetonitrile. Finally, 2 mmol of TBHP (5.0–6.0 M in decane) was added, and the
◦
reaction was heated to 30 C for 6 h. Then, 15 mL of ethyl acetate was added, and the reaction mixture
evaporated. It was then directly loaded onto silica (Pet ether: EtOAc (60:1)) to give the desired product
1
in 80% isolated yield. H-NMR (300 MHz, Chloroform-d):
δ 6.83 (d, J = 7.6 Hz, 1H), 6.52 (d, J = 7.6 Hz,
1H), 3.89 (s, 2H), 2.39 (s, 3H), 2.15 (s, 3H). 13C-NMR (75 MHz, Chloroform-d):
δ 138.31, 130.58, 127.62,
123.77, 121.08, 120.15, 17.75, 17.32. HRMS calcld 162.0905, found 162.0900.
3-azido-(1,10-biphenyl)-2-amine. 2-Phenylaniline (1 mmol) was added to a flame-dried Schlenk tube
containing 0.10 mmol of CuBr. Then, TMSN3 (2 mmol) was added, followed by addition of 4 mL
of freshly distilled acetonitrile. Finally, 2 mmol of TBHP (5.0–6.0 M in decane) was added, and the
◦
reaction was heated at 30 C for 6 h. Then, 15 mL of ethyl acetate was added, and the reaction mixture
evaporated. It was then directly loaded onto silica (Petroleum ether: ethylacetate (60:10)) to give the
1
desired product in 60% isolated yield. Analytical data matched literature [22]. H-NMR (400 MHz,
Chloroform-d):
δ 7.48–7.34 (m, 5H), 7.05 (dd, J = 7.8, 1.5 Hz, 1H), 6.94 (dd, J = 7.6, 1.5 Hz, 1H), 6.85 (t,
J = 7.7 Hz, 1H), 3.94 (s, 2H).
2-azido-6-methoxy-3-(trifluoromethyl)aniline. Using the same general procedure, isolated in 80% purity
1
after eluting with 6:1 Hex:EtOAc. H-NMR (300 MHz, Chloroform-d)
δ 7.02 (d, J = 8.7 Hz, 1H), 6.67 (d,
J = 8.6 Hz, 1H), 4.19 (s, 2H), 3.90 (s, 3H). 19F-NMR (282 MHz, Chloroform-d): δ −59.44. HRMS calcld
232.0572, found 232.0545.

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4.2. Catalytic Reactions to Give Azobenzenes
For the catalytic reactions, the following general procedure was followed: All reactions were
carried out with 0.3 mmol of azide. [CoII(TPP)] (5 mol%) was transferred to a flame-dried Schlenk
tube, after which the tube was evacuated and back-filled with dinitrogen three times. In a separate
Schlenk tube containing 0.3 mmol of the azide, 4 mL of toluene was added to dissolve the azide.
Using a syringe, this solution was transferred to a Schlenk tube containing the [CoII(TPP)] catalyst.
The reaction mixture was then bubbled with dinitrogen for 15 min, after which it was heated to 90 ◦C
for 18 h.
The reaction mixture was concentrated and was directly loaded onto a glass baked silica plate and
ran using a suitable solvent (or solvent mixtures). The desired compound always gave a characteristic
bright orange/red band on the silica plate.
A
: (E)-2,20-(diazene-1,2-diyl)dianiline. Using the general procedure (Prep-TLC using pure DCM), 80%
1
isolated yield. Analytical data matched literature [21]. H-NMR (400 MHz, Chloroform-d):
δ 7.68 (dd,
J = 8.0, 1.6 Hz, 1H), 7.23–7.06 (m, 1H), 6.93–6.63 (m, 2H), 5.48 (s, 2H). 13C-NMR (126 MHz, CDCl3)
δ
143.11, 137.73, 131.37, 124.29, 117.66, 117.04. HRMS calcld 211.1106, found 211.1106.
C: (E)-6,60-(diazene-1,2-diyl)bis(2-(tert-butyl)aniline). Using the general procedure (Prep-TLC using
1
DCM), 98% isolated yield. H-NMR (300 MHz, Chloroform-d):
δ 7.50 (dd, J = 8.1, 1.4 Hz, 1H), 7.40–7.24
(d, 7.8 1H), 6.70 (t, J = 7.9 Hz, 1H), 1.49 (s, 9H). 13C-NMR (75 MHz, CDCl3):
δ 145.00, 140.29, 135.73,
129.74, 117.76, 115.97, 35.10, 30.25. HRMS calcld 296.2001, found 296.2005.
0
D: (E)-6,6 -(diazene-1,2-diyl)bis(2-isopropylaniline). Using the general procedure (Prep-TLC using DCM),
1
98% isolated yield. H-NMR (300 MHz, Chloroform-d):
δ 7.52 (dd, J = 8.1, 1.5 Hz, 1H), 7.19 (dd, J = 7.6,
1.4 Hz, 1H), 6.77 (t, J = 7.8 Hz, 1H), 5.24 (s, 2H), 3.10–2.83 (m, 1H), 1.32 (d, J = 6.8 Hz, 6H). 13C-NMR
(75 MHz, CDCl3): 142.53, 138.65, 134.21, 117.61, 117.30, 27.67, 22.34. HRMS calcd. 325.2392 for
δ
C20H28N4, found 325.2394.
E: (E)-3,30-(diazene-1,2-diyl)bis(([1,10-biphenyl]-2-amine)). Using the general procedure (Prep-TLC using
1
DCM: hexane = 1:1), 60% isolated yield. H-NMR (400 MHz, Chloroform-d):
δ 7.70 (dd, J = 8.1, 1.6 Hz,
1H), 7.60–7.48 (m, 5H), 7.19 (dd, J = 7.2, 1.6 Hz, 1H), 6.86 (t, J = 7.7 Hz, 1H), 5.55 (s, 2H). 13C-NMR
(101 MHz, Chloroform-d): 141.75, 138.80, 138.09, 132.64, 129.45, 129.35, 129.17, 129.11, 127.72, 121.42,
117.32. HRMS calcld 364.1688, found 364.1645.
δ
F
: (E)-6,60-(diazene-1,2-diyl)bis(2-bromoaniline). Using the general procedure (Prep-TLC using DCM:
1
hexane = 1:1), 48% isolated yield. H-NMR (400 MHz, Chloroform-d):
δ 7.64 (dd, J = 8.1, 1.5 Hz, 1H),
7.48 (dd, J = 7.8, 1.5 Hz, 1H), 6.70 (t, J = 7.9 Hz, 1H), 6.09 (s, 2H). HRMS calcld 367.9272, found 367.9256.
TD-DFT Calculations
The UV-Vis transitions of compound
triplets = false), as implemented in the ORCA package at the b3-lyp level (RIJCOSX) using the
def2-TZVP basis set [28 31]. We used COSMO [32 36] dielectric solvent corrections ( = 8.93; CH2Cl2)
F were calculated with TD-DFT (nroots = 100; maxdim = 600;
–
–
ε
to account for solvent effects.
5. Conclusions
In conclusion, we have reported a unique base metal-catalyzed dimerization reaction of
substituted o-amino phenyl azides that is a general method for synthesizing o-amino-azobenzenes.
Mechanistically, these reactions proceed via azide activation at the catalyst, leading to formation of
porphyrin-Co(III)-nitrene radicals. These nitrene radical intermediates perform H-atom abstraction
form the ortho amine substituent to form the OPDI reactive intermediates, which couple to form
azobenzenes. This protocol is more efficient for azides with electron-donating substituents than those
with electron-withdrawing substituents. The synthesized azobenzenes are bathochromically shifted

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compared to the unsubstituted azobenzenes. Based on the crystal structure, the ortho-amine substituent
is seen to participate in H-bonding interactions with the azo N atom. This can be expected to cause
hindered rotation for the trans- to cis- isomerization and thermal relaxation from cis- to trans- isomer can
be expected to be fast. One of the possible applications of these o-amine substituted compounds may
be as candidates for use as photo-responsive acids/bases. At the same time, the amine functionality in
these compounds can act as a connection point for further functionalization.
Supplementary Materials: Supplementary materials are available on line.
Author Contributions: M.G. conceived, designed and performed the experiments. B.d.B. conceived the
experiments and analyzed the data.
Funding: We thank the Netherlands Organization for Scientific Research (NWO-CW VICI project 016.122.613) for
financial support.
Acknowledgments: We thank W.I. Dzik (HIMS) for help with X-ray crystallography and Ed Zuidinga (HIMS) for
help with mass spectrometry.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds are not available from the authors.
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