Convenient semihydrogenation of azoarenes to hydrazoarenes using H2

Article abstract of DOI:10.1039/d1ob00850a

The high atom-economical and eco-benign nature of hydrogenation reactions make them much more superior to conventional reduction and transfer hydrogenation. Herein, a convenient and highly selective hydrogenation reaction of azoarenes using molecular hydrogen to access diverse hydrazoarenes is reported. The present catalytic method is general and operationally simple, and it operates under exceedingly mild conditions (room temperature and 1 atm of hydrogen pressure). The reusability of catalysts used in this method is also successfully demonstrated.

Full text of DOI:10.1039/d1ob00850a

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Convenient semihydrogenation of azoarenes to
hydrazoarenes using H2†
Cite this: Org. Biomol. Chem., 2021,
19, 5289
Manoj K. Sahoo,‡a Ganesan Sivakumar,‡a Sanjay Jadhav,b Samrin Shaikhb and
Received 30th April 2021,
Accepted 18th May 2021
a
Ekambaram Balaraman
*
DOI: 10.1039/d1ob00850a
rsc.li/obc
The high atom-economical and eco-benign nature of hydrogen- unselective.10 The research groups of Shiraishi,11a Wu,11b and
ation reactions make them much more superior to conventional Zhu11c have independently reported visible-light photocatalytic
reduction and transfer hydrogenation. Herein, a convenient and transfer hydrogenation of azobenzenes to hydrazoarenes.
highly selective hydrogenation reaction of azoarenes using mole- Notably, the research groups of Li12a and Kinjo12b have inde-
cular hydrogen to access diverse hydrazoarenes is reported. The pendently reported catalytic hydrogenation of azoarenes using
present catalytic method is general and operationally simple, and it boranes as the transfer hydrogenating reagent. Borylation or
operates under exceedingly mild conditions (room temperature silaborations of azoarenes followed by hydrolysis to access
and 1 atm of hydrogen pressure). The reusability of catalysts used hydrazobenzene is reported by the research group of
in this method is also successfully demonstrated.
Spencer.13
Recently,
the
research
groups
of
Landaeta,14a
Hydrazoarenes are important industrial chemicals used in the
manufacture of dyes and pigments.1 These chemicals have
numerous applications in pharmaceuticals (Fig. 1),2 supramo-
lecular chemistry,3 and synthesis of highly substituted aniline
derivatives.4 Conventionally, hydrazoarenes are prepared by
selective reduction of azo compounds; however, the formation
of over-reduced anilines is of primary concern. Classical
reduction methods of azoarenes involve the use of a stoichio-
metric amount of highly reactive metals/metal salts such as
Mg, Zn, SmI2, or toxic trialkyltin hydride, which produce
copious metal salt waste (Scheme 1).5 Selective reduction of
azo compounds to hydrazobenzenes using hydrazine, borane
or sodium dithionite as reducing agents is also established.6–8
Wang and co-workers have reported the reduction of azoben-
zenes using NaBH4 as a reductant and FeSx/Al2O3 as a cata-
lyst.9 Unfortunately, this process has limited substrate scope
and poor functional group compatibility due to the use of a
stoichiometric amount of the reducing agent. The Schmöger
research group reported palladium-catalyzed hydrogenation of
azoarenes using hydrazine and H2 gas; however, the reaction is
Radosevich,14b and Cornella14c have independently reported
catalytic transfer hydrogenation of azoarenes to hydrazoben-
zenes using ammonia-borane as an efficient reducing agent.
Fig. 1 Importance of hydrazobenzenes (selected examples).
aDepartment of Chemistry, Indian Institute of Science Education and Research
(IISER) Tirupati, Tirupati-517507, India. E-mail: eb.raman@iisertirupati.ac.in
bOrganic Chemistry Division, Dr Homi Bhabha Road, CSIR-National Chemical
Laboratory (CSIR-NCL), Pune-411008, India
†Electronic supplementary information (ESI) available: Experimental procedures
analytical data. See DOI: 10.1039/d1ob00850a
‡These authors contributed equally to this work.
Scheme 1 Hydrogenation/reduction of azoarenes.
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The Landaeta and Radosevich groups have used a phosphorus the absence of Pd-catalyst (Table 1, entry 2). The role of an
(III) based precatalyst whereas the Cornella group has used a Bi additive is very important for this reaction. Among the various
(I)-pincer complex as the catalyst. However, the use of an additives screened under standard reaction conditions, pyri-
expensive reductant in excess amounts and prolonged reaction dine was found to be optimal (Table 1, entries 1, and 4–6). The
time are the major limitations. Thus, these methods are absence of additive or lowering of its mol% resulted in a lower
neither economical nor environmentally friendly. In this product yield, and the rate of the reaction was sluggish
regard, the development of a general catalytic method is (Table 1, entries 3 and 7). We did not observe any other side
highly desired for selective hydrogenation of azoarenes15,16 to products except for hydrazobenzene, aniline, and unreacted
hydrazoarenes using H2 gas. Typically, catalytic hydrogenation azobenzene under our catalytic conditions.
reactions produce few or zero by-products. The high atom-
Among several solvents screened, methanol was found to
economical and eco-benign nature of hydrogenation reactions be optimal for this reaction and offered the maximum yield of
make them much more superior to conventional reduction the product (Table 1, entries 1, 9–11). It is well understood
and transfer hydrogenation. Herein, an efficient, highly selec- that hydrogen adsorption and activation have been accelerated
tive hydrogenation of azoarenes at room-temperature using by protic solvents.17 In addition, several possible reasons can
molecular hydrogen to access diverse hydrazoarenes is demon- be proposed to explain the effect of solvents, such as the solu-
strated. The present catalytic method is operationally simple bility of hydrogen in reaction media, competitive adsorption of
and operates under mild conditions. This direct hydrogenation solvent at active catalyst sites, and intermolecular interaction
exhibits a wide substrate scope and excellent functional group between the reactant and solvent molecules.18 Indeed, the
compatibility that is easy to scale up.
other possibility is that the azobenzene protons hydrogen-
Initially, a simple unsubstituted azobenzene 1a was chosen bond with methanol thereby activating the –NvN– bond
as a model substrate for the catalytic hydrogenation reaction. (diazo bond). A similar solvent effect was also observed by
After careful investigation of various parameters, such as the Hirota in the Pd/C-catalyzed cleavage of silyl ethers.19 Notably,
use of catalysts and their loading, additives, and solvents other catalysts including Pd/Al2O3 were found unsuitable for
(Table 1), the optimal reaction conditions for the selective this selective hydrogenation reaction (Table 1, entries 1,
hydrogenation of azobenzene (1a) to hydrazobenzene (2a) were 12–16). A decrease in Pd/C catalyst loading reduced the yield of
determined (Table 1, entry 1; 0.2% loading of Pd/C, 10 mol% 2a (Table 1, entry 18). The research groups of Groppo20 and
of pyridine, MeOH, and 1 atm of H2). A series of control experi- Xia21 have independently demonstrated the effect of surface
ments were carried out to confirm the necessity of each of the chemistry on the performances of Pd-based catalysts sup-
reaction components such as the catalyst, additive or co-cata- ported on activated carbons. Based on these reports, we
lyst, and solvent. No formation of the product was observed in believe that a weak interaction between planar p-electrons of
sp2 hybridized N-atom and the carbon support helps the
adsorption of azocompounds on the carbon matrix, and thus
Pd/C shows enhanced activity in the semihydrogenation of
azoarenes.
Table 1 Optimization studiesa
Having optimal reaction conditions in hand, the scope of
various aromatic azoarenes was investigated under the opti-
mized reaction conditions. The present direct hydrogenation
showed a wide substrate scope and broad functional group tol-
Entry
Variation from initial conditions
Yield % (2a : 2a′)b
erance under operationally facile conditions. This reaction
offers a mild and environmentally benign approach for the
library synthesis of 1,2-diarylhydrazine derivatives in good to
excellent yields (up to 96%). Notably, the electron-donating as
well as electron-withdrawing groups at different positions of
the aromatic ring of the 1,2-diaryldiazene derivatives did not
affect the reactivity in the catalytic hydrogenation. The unsym-
metrical ortho-substituted azobenzene derivatives (o-Cl and
o-Et) proceeded smoothly to selectively afford the semi-hydro-
genated products 2b and 2c in excellent yields. Similarly,
unsymmetrical meta-substituted substrates (–F, –Cl, and
–NHAc) provided the corresponding hydrogenated products in
good to excellent yields (up to 95%; Table 2, products 2d–2f).
The azoarenes bearing electron-withdrawing groups at the
para-position of the aryl ring, such as –F, –Cl, –Br, –CF3, and
–CO2Me smoothly proceeded the hydrogenation reaction
under the optimal reaction conditions and led to the corres-
ponding products in 69%–96% isolated yields (Table 2, pro-
1
2
3
4
5
6
7
8
None
98 (94)c
NR
23
56 (50 : 50)
89
60
57
In the absence of Pd/C
In the absence of pyridine
2-Methylpyridine instead of pyridine
DMAP instead of pyridine
Et3N instead of pyridine
5 mol% of pyridine
100 mol% of pyridine
Toluene instead of MeOH
THF instead of MeOH
DMC instead of MeOH
Ru/C instead of Pd/C
Rh/C instead of Pd/C
Pt/C instead of Pd/C
36
45
9
10
11
12
13
14
15
16
17
Trace
NR
Trace
40 (50 : 50)
68 (36 : 65)
28
Pd/Al2O3 instead of Pd/C
Pd(OAc)2 instead of Pd/C
0.1 mol% of Pd loading
NR
72
a Reaction conditions: 0.5 mmol of 1a, 2.1 mg of 5 wt% Pd/C (0.2% of
Pd loading), 10 mol% pyridine, 10 mL of anhydrous MeOH, H2 (1
atm), room temperature, 15 min. b NMR yield using 1,4-dibromobu-
tane as an internal standard. c Isolated yield. NR = no reaction.
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Table 2 Highly selective direct hydrogenation of azoarenesa
Table 3 Highly selective direct hydrogenation of heteroaromatic
azoarenesa
a Reaction conditions: 0.5 mmol of 3, 4.2 mg of 5 wt% Pd/C (0.4% of
Pd loading), 10 mol% pyridine, 10 mL of anhydrous MeOH, H2 (1
atm), room temperature, 30 min and the represented yields are iso-
lated yields.
respectively (Table 3). Interestingly, a good result was obtained
in the case of 3a, which bears two pyridine groups. This result
indicates that the rate adsorption of the diazo bond on Pd/C is
better than the pyridyl group. Next, we have successfully
demonstrated the scalability of this catalytic hydrogenation
under mild conditions (Table 4). In this regard, the present
Pd/C catalyzed semihydrogenation of azoarenes was tested for
a gram-scale synthesis of 2a, 2h, 2n, and 4a (5.0 mmol scale)
and it worked excellently and afforded the corresponding 1,2-
diaryldiazene derivatives in very good yields after a reaction
time of 25 to 40 min.
The significant advantage of heterogeneous catalysts over
soluble homogeneous catalysts is their ability to easily separate
and recycle. To demonstrate the versatility and the cost-effec-
tiveness of the present catalytic system, a reusability test of the
heterogeneous Pd/C catalyst was carried out. Thus, the recov-
ered heterogeneous Pd/C catalyst exhibits remarkable activity,
and its reusability was tested up to six consecutive cycles
(Fig. 2a). Indeed, no deactivation of the catalyst was observed.
Time-dependent experimental analysis was carried out to
monitor the progress of the hydrogenation reaction (Fig. 2b).
Monitoring the progress of the direct hydrogenation indicated
that the consumption of azoarene 1a follows an exponential
decay.
a Reaction conditions: 0.5 mmol of 1a–u, 2.1 mg of 5 wt% Pd/C (0.2%
of Pd loading), 10 mol% pyridine, 10 mL of anhydrous MeOH, H2 (1
atm), room temperature, 15 min and the represented yields are iso-
lated yields. b 30 min. c 4.2 mg of Pd/C (0.4% of Pd loading). d 6.3 mg
of Pd/C (0.6% of Pd loading).
ducts 2g–2j, and 2n). It is noteworthy that there is no for-
mation of dehalogenated products under the present catalytic
conditions. Similarly, substrates with electron-donating groups
also showed excellent reactivity towards the semihydrogena-
tion reaction. Thus, electron-rich para-substituted azoarenes
(p-EtO, p-NHPiv, and p-OPiv) proceeded well and yielded the
corresponding 1,2-diarylhydrazine derivatives in excellent
yields (Table 2, products 2k–2m). Significantly, the reducible
acyl group was unaffected under our reaction conditions.
Thus, the azoarenes 1o and 1u selectively yielded the –NvN–
bond hydrogenated products in very good yields (products 2o
and 2u in 88% and 75% yields, respectively). Notably, both
symmetrical and unsymmetrical di-substituted azoarenes were
reacted efficiently under the optimized conditions to yield the
corresponding hydrazo derivatives in good to excellent yields
(Table 2, products 2p–2t).
Table 4 Direct hydrogenation of azoarenes: gram-scale synthesisa
R
X
Time (min)
Product (yield %)b
H
p-Cl
p-CO2Me
H
C
C
C
N
25
25
25
45
2a (94%)
2h (89%)
2n (84%)
4a (74%)
Not only is this catalytic method limited to the aromatic
azoarenes but also the heteroaromatic azoarenes are selectively
hydrogenated under the optimal conditions and yielded the
desired products. Thus, the heteroaromatic azo compounds 3a
and 3b underwent –NvN– hydrogenation smoothly and gave
the corresponding products 4a and 4b in 83% and 90%,
a Reaction conditions: substrate 5.0 mmol, 42 mg of 5 wt% Pd/C (0.4%
of Pd loading), 10 mol% pyridine (40 mL), 100 mL of anhydrous
MeOH, H2 (1 atm), room temperature. b The represented yields are iso-
lated yields.
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In summary, here we have reported a general and efficient
catalytic hydrogenation of azoarenes to hydrazoarenes under
mild, eco-benign conditions. The use of a reusable Pd/C cata-
lyst, high selectivity, broad substrate scope, functional group
compatibility and the absence of copious waste products in
this direct hydrogenation make our work attractive.
Fig. 2 (a) Recyclability test (left). (b) Kinetic profile of hydrogenation of
1a (right).
Conflicts of interest
There are no conflicts to declare.
The research group of Nag has studied the formation of pal-
ladium hydride in a carbon-supported palladium catalyst.22
Notably, the ability to absorb hydrogen in the subsurface region
of Pd/C has been explained by the simple Horiuti–Polanyi
mechanism.23 Indeed, a catalytic amount of pyridine accelerates
the H-atom transfer by increasing electron density on the metal
center and thus increases the catalytic activity in a controlled
manner.24 Also, pyridine is known to poison by partially pre-
venting access to the metal center. We believe after semihydro-
genation of azobenzene that the additive pyridine prevents the
over hydrogenation of hydrazobenzene to aniline by preventing
the sterically hindered hydrazobenzene molecules from access
to Pd-center. To verify this, we have performed hydrogenation of
hydrazo benzene (2a) in the presence and absence of a catalytic
amount of pyridine. It was observed that in the presence of pyri-
dine, the hydrogenation of 2a to aniline (2a′) is slower (13%
yield of aniline 2a′). However, in the absence of pyridine (only
Pd/C), hydrogenation proceeded efficiently and 2a′ was obtained
in 88% yield.25 Recently, Zaera and coworkers demonstrated the
effect of additives and the surface chemistry of transition-metal
catalysts in the hydrogenation catalysis.26
Acknowledgements
This research work was supported by SERB, India (Grant No.
CRG/2018/002480/OC). EB thanks to CSIR-NCL, Pune for infra-
structure facilities, and also acknowledges the SwarnaJayanti
Fellowship grant (DST/SJF/CSA-04/2019-2020 and SERB/F/
5892/2020-2021). GS thanks the IISER-Tirupati for the
fellowship.
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azoarene using H2.
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