C–H bond cyanation of arenes using N,N-dimethylformamide and NH4HCO3 as a CN source over a hydroxyapatite supported copper catalyst?

Article abstract of DOI:10.1039/c6cy01536k

A hydroxyapatite supported Cu catalyst [HAP:Ca₅(PO₄)₃(OH)] has been found to be an efficient and reusable heterogeneous catalyst for safe cyanation of C–H bonds of hetero aryl compounds. The combination of NH₄HCO₃ and DMF is identified as a CN source under mild reaction conditions. 10 wt% Cu/HAP offered good to excellent yields compared to Ru/HAP and Pd/HAP catalysts. The surface basicity and Cu metal surface area of the catalysts played a significant role in the cyanation reaction through C–H bond activation. The catalyst was recovered and reused for five cycles showing consistent activity and selectivity. The physicochemical characteristics of the catalysts are rationalized by H₂-TPR, BET-SA, XPS, TEM and N₂O titration techniques.

Full text of DOI:10.1039/c6cy01536k

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Catalysis Science & Technology
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C–H bond cyanation of arenes using N, N-dimethylformamide and
NH HCO as CN source over hydroxyapatite supported copper
catalyst
4
3
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a
a
DOI: 10.1039/x0xx00000x
Boosa Venu , Bilakanti Vishali , Gutta Naresh , Velisoju Vijay Kumar , Medak Sudhakar , Ramineni
a
b
b
a,
Kishore , Jorge Beltramini , Muxina Konarova and Akula Venugopal *
www.rsc.org/
Cu supported on hydroxyapatite [HAP: Ca
5
(PO
4
3
) (OH)] catalyst has been found to be an efficient and reusable
heterogeneous catalyst for safe cyanation of C-H bonds of hetero aryl compounds. Combination of NH
4
HCO and DMF are
3
identified as CN source under mild reaction conditions. A 10wt%Cu/HAP offered good to excellent yields compared to
Ru/HAP and Pd/HAP catalysts. The surface basicity and Cu metal surface area of the catalysts played a significant role on
the cyanation reaction through C-H bond activation. The catalyst was recovered and reused for five cycles that showed
consistent activity and selectivity. The physicochemical characteristics of the catalysts are rationalized by H
2
-TPR, BET-SA,
XPS, TEM and N O titration techniques.
2
2
2
applications for cyanation reactions.
2
Organocyanating
24
3
reagents such as nitromethane,
26,27
tosyl cyanide, ethyl
29-
2
cyanoacetate, isonitrile,
5
28
benzyl cyanide, acetonitrile,
3
1
32
AIBN (2,2′-azobisisobutyronitrile) and NCTS (N-cyano-N-
Introduction
3
3-35
phenyl-p-toluenesulfonamide)
are reported recently.
The methodology for the synthesis of aryl nitriles is an area of
great interest. Nitrile compounds have wide range of
applications in synthetic organic chemistry due to the fact that
these nitriles are valuable in installation of functionalities such
as aldehydes, amines, amidines, tetrazoles, acids and acid
Significant, amount of work on cyanation reactions are
reported by Chang and co-workers. They have used DMF and
ammonia or ammonium salts as the combined ‘CN’ source to
realize the cyanation of the carbon–hydrogen (heteroatom)
3
6
1
-3
bond.
ammonium bicarbonate and DMF (or) DMSO as the combined
CN’ source is also achieved. These methods on cyanation
Cyanation of aromatic halides by employing
derivatives. The aryl nitriles are also key motifs in natural
products, pharmaceuticals, agrochemicals, dyes and electronic
4
materials. Aryl nitriles are often synthesized from aryl halides
‘
reactions involved the combined ‘CN’ source contributing from
DMF or DMSO provide the ‘C’ unit of ‘CN’ while the ‘N’ unit
with stoichiometric amounts of CuCN which is being used in
5
–9
Rosenmund–von Braun reaction.
Unfortunately, use of
3
6,37
comes from ammonia or ammonium salts.
examined the cyanation of aromatic C–H bonds by using a
combination of NH HCO and DMSO as ‘CN’ source over Pd(II)
We have
stoichiometric amounts of CN sources would lead to equimolar
amounts of heavy metal waste. Therefore, transition metal-
catalyzed methods have been explored, such as palladium,
4
3
3
8
1
0,11
12,13
supported on Mg–La mixed oxide catalyst. Most of these
processes are involved either the use of expensive noble
metals or the non-eco-friendly reagents. Therefore
development of inexpensive base metal catalysts for the
cyanation of aryl C–H bonds has become a topic of interest.
Herein, we report the supported Cu catalysts for the cyanation
nickel and copper-based catalysts, using KCN,
NaCN,
as cyanating agents. However,
these cyanation compounds have several drawbacks e.g. KCN
and NaCN are highly toxic; Zn(CN) leads to heavy metal waste
and Me SiCN is sensitive to moisture and easily liberate
1
4–16
17–21
Me
3
SiCN,
and Zn(CN)
2
2
3
hydrogen cyanide. These limitations seriously restrict their
4 3
of aromatic C–H bonds by using a combination of NH HCO
and DMF as the ‘CN’ source to provide aromatic nitriles in
good to excellent yields under mild reaction conditions. In the
comparative analysis Cu/HAP demonstrated better nitrile yield
than the Ru/HAP and Pd/HAP catalyst.
5 4 3
Hydroxyapatite [Ca (PO ) (OH)] spawned great interest in view
of its potentials usefulness as biomaterials, adsorbents, ion-
3
9
exchangers and as catalyst support. Different transition
metals supported on hydroxyapatite catalysts have been
explored as an effective heterogeneous catalysts in the
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ARTICLE
oxidative cleavage of alkenes, hydrogenation reactions,
Journal Name
4
0
41
The X-ray diffraction patterns of HAP and Cu/HAP catalysts are
42
oxidative coupling of alcohols and amines.
The reported in Figure 1. The diffraction lines at 2θ = 25.8°, 29.1°,
hydroxyapatite has also been studied as a catalyst support for 31.9°, 32.2°, 33.1°, 34.1°, 40.1°, 46.9°, and 49.1° are attributed
gold and ruthenium in water gas shift reactions as well as a to Ca (PO (OH) phase (ICDD # 86-07640) and the diffraction
stand-alone catalyst for the dehydrogenation and dehydration signals due to CuO phase are observed at 2θ = 35.5°, 38.67°
5
4 3
)
4
3-46
of alcohols.
Recently, we have reported, highly basic Mg- (ICDD # 45-0937). The XRD patterns clearly showed that the
LaO mixed oxide supported Pd as a solid base catalyst for the crystallite size of CuO is increased with increase in Cu loading.
3
C-H bond activation of arenes in the cyanation reaction. Kou The CuO phase is clearly seen at above 5wt%Cu/HAP samples.
8
-
1
-1
mol (gCu) h with regio-isomers No changes due to crystal structure and crystallite size of Cu in
et al reported a rate of 848
57:33 ratio of) 483
yl)benzonitrile and 365
µ
-
1
-1
(
µ
mol (gCu
)
h
of 2-(pyridin-2- the fresh and used form of 10wt%Cu/HAP emphasizing the
-1
-1
h of 2,6-dicyano stability of the catalyst under the reaction conditions applied.
µ
mol (gCu
)
3
1
phenylpyridine. In the copper mediated direct aryl C-H
-1
-1
cyanation reaction; Xu et al reported 647 µmol (g ) h of 2-
Cu
3
pyridin-2-yl)benzonitrile. Kim et al found 293
2
-1 -1
µmol (g ) h
Cu
(
of 4-methoxybenzonitrile in the conversion of 4-
3
6c
methoxyphenylboronic acid.
In the present study an
enormous increase in the rate of 2-(pyridin-2-yl)benzonitrile
-1
-1
ca. 1184 µmol (g ) h is observed over a solid base catalyst
Cu
composed of 10wt%Cu/HAP. In this investigation, we found
hydroxyapatite as a support material for Cu for the safe
cyanation of hetero aryl compounds. The Cu/HAP catalyst
displayed moderate to strong basic sites on the catalyst
surface. The physico chemical characteristics of the Cu/HAP
catalysts are rationalized by various adsorption and
spectroscopic techniques and the catalytic activities are
correlated with cyanation of 2-phenylpyridine compounds
under mild reaction conditions.
Experimental
Preparation of catalysts
5 4 3
The hydroxyapatite Ca (PO ) (OH) was prepared according to
4
3
an earlier report. In a typical method, the solution of calcium
nitrate tetrahydrate (0.326 mol) in 200 mL water was brought
to a pH of 11–12 with concentrated (25%) ammonia solution
and thereafter diluted to 500 mL. A solution of diammonium
hydrogen phosphate (0.318 mol) in 300 mL water was brought
to a pH of 11–12 with concentrated (25%) ammonia solution
and thereafter diluted to 600 mL. Under vigorous stirring the
phosphate solution was added drop wise to the solution of the
calcium salt over a period of 2h to produce a milky white
precipitate, which was then stirred and boiled for 30 min. The
precipitate was washed thoroughly, filtered and dried at 100
H -TPR analysis of Cu/HAP samples
2
°
C overnight and then calcined in static air at 500 °C for 5h
here after denoted as HAP. The HAP supported metal catalysts
were prepared by a wet impregnation method. The required
amount of metal precursor [(RuCl
3 2 2 3 2 2
xH O, PdCl , Ni(NO ) 6H O,
and Cu(OAc)2. O AR Grade, supplied by Sigma–Aldrich] was
H
2
taken to give corresponding weight percent of metal dissolved
in double distilled water and mixed with HAP power. The
solvent is then evaporated under constant stirring, followed by
oven drying at 120 °C for 12h and subsequently calcined in
static air at 450°C for 5h at a ramping rate of 5°C /min.
Figure 2: H
supported on Ca
2
-TPR profiles of (a) 2.5 (b) 5.0 (c) 7.5 (d) 10.0 and (e) 12.5wt% Cu
5
(PO
4
)
3
(OH) samples
XRD analysis of fresh and used catalysts
2
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ARTICLE
The H
2
-TPR profiles of Cu supported on Ca
5
(PO
4
)
3
OH samples X-ray photoelectron spectroscopic analysis
presented in Figure 2 and their corresponding H
2
uptakes are
The binding energies obtained XPS analysis revealed that the
2+
Cu species are stabilized on HAP surface. Figures 4A and 4B
reported in Table 1. It shows that CuO undergone two stage
reduction in all the samples. The low temperature reduction
signals (230-270 °C) is attributed to dispersed CuO and the
high temperature peak (270-375 °C) is attributed to bulk or
shows Cu 2p and O 1s XPS of fresh and used 10wt%Cu/HAP
2
catalyst. The Cu species are present on the catalyst surface
+
which is confirmed by signals at binding energies 933.7 eV and
48
4
7
large size clusters of CuO species. Upon increasing the Cu 953.4 eV of Cu 2p3/2 and Cu 2p1/2respectively. These spectral
2
+
loading, the Tmax shifted to higher temperature which is an lines ascribed to Cu are retained on the catalyst surface even
indication of bigger CuO crystals and broadness of the signal is after 4 cycles of reuse.
probably due to CuO strongly interacted with hydroxyapatite.
2
Increase in H uptake with an increase in CuO loading suggests
the bulk property of the TPR analysis [Table 1].
2
CO -TPD analysis of the Cu/HAP samples
Figure 4: XPS of (A) Cu 2p (B) O 1s spectra of 10wt%Cu/HAP (a) fresh and (b) used
catalyst.
Transmission electron microscopic analysis
st
TEM images of the fresh and used (after 1 cycle) of
1
0wt%Cu/HAP samples are reported in Figure 5. The copper
particles are spherical in shape with uniform distribution in
both fresh and used form. The average particle size of copper
is found to be 26 nm and 29 nm on fresh and used catalysts,
respectively. The particle sizes of copper in the fresh and used
form are more or less similar, thus suggesting the stability of
the copper species in the cyanation of aryl compounds.
Figure 3: CO
2 5 4 3
-TPD profiles of Cu supported on Ca (PO ) OH (a) 0.0 (b) 2.5 (c) 5.0 (d) 7.5
(
e) 10.0 (f) 12.5wt% catalysts.
The TPD of CO profiles of pure HAP and the Cu loaded HAP
2
samples are reported in Figure 3. Figure 3, shows that pure
HAP indicated two peaks corresponding to weak and moderate
basic sites. Doping of copper on HAP the basicity of the
catalysts is increased and Tmax is shifted to high
4
1
temperatures. The shift in Tmax towards high temperatures is
gradually increased with increase in Cu content. The numbers
of basic sites are found to increase with Cu loading up to Figure 5: TEM images of the 10wt%Cu/HAP: (A) fresh and (B) used catalyst
st
(recovered after 1 cycle).
10wt%Cu/HAP.
Table 1: Physicochemical characteristics of the Cu supported on Ca
5 4 3
(PO ) OH samples.
Reaction scheme
d
Cu
BET
surface
area
H
2
uptake
CO
2
N
2
O uptake
S
Cu
a
c
2
(
wt%)
(μmol/gcat
)
uptake
(μmol/gcat
)
/ m
b
)
-1
on
(µmol/gcat
g
2
-1
HAP
(m g )
54.0
43.0
35.0
30.0
27.5
25.4
0
2
5
7
.0
.5
.0
.5
nd
173
181
289
295
451
nd
1.6
nd
232.2
374.5
454.4
530.0
735.0
5.30
6.44
7.70
8.99
7.18
3.9
7.0
5 4 3
Scheme 1: Synthesis of aryl nitrile over Cu/Ca (PO ) OH.
1
1
0.0
2.5
10.9
10.8
339
Optimization of reaction parameters
a
b
nd: not determined; : measured from H
2
-TPR; : measured from TPD of CO
2
;
c,d
:
The reaction parameters are optimized by using 2-
phenylpyridine as the model substrate. Using 150mg of
Cu/HAP catalyst, a combination of NH HCO (1.5 mmol) and
2
measured from N O titration method.
4
3
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DMSO (2 mL) as the cyanating agent, the desired product i.e. nitrogen source for cyanation reaction when compared to
-(pyridin-2-yl)benzonitrile is obtained with 30% yield (Table 2, ammonia solution (Table 2, entry 12). The reaction
2
entry 1). Encouraged by this result, several experiments are temperature had strongly influenced the catalytic activity as
conducted by altering the oxidant, nitrogen source and the yield of the product is decreased to 71% at 120 °C and to
solvents. The results are summarized in Table 2.
48% at 100 °C (Table 2, entries 13 and 14). At a temperature of
40 °C; the yield is decreased to 52% when the reaction time
1
Table 2: Screening of reaction parameters
maintained for 12h and similar situation observed wherein the
yield further fallen to 30% after a reaction time of 6h (Table 2,
N
Yield
Entry
Catalyst
Oxidant/mmol
Solvent
source/mmol
NH HCO /1.5
NH HCO /1
NH
NH
(%) entries 15 and 16). When the reaction is performed under N
2
atmosphere, only 20% yield observed, indicating that O
oxidant which is essential for the reaction (Table 2, entry 17).
The Al supported CuO catalyst showed very low activity
2
as the
1
2
3
4
10wt%Cu/HAP
10wt%Cu/HAP
10wt%Cu/HAP
10wt%Cu/HAP
O
O
2
2
4
3
DMSO
DMF
DMF
DMF
30
78
0
4
3
2 3
O
Ag
2
O/2
4
HCO
HCO
3
3
/1.5
/1.5
with 10% yield (Table 2, entry 18).
TBHP(70%
4
0
aqueous)/2
Table 3, reveals the dependence of cyanation activity over
various loadings of copper on HAP catalysts in the C-H bond
cyanation of arenes at 140 °C. The nitriles formation is found
5
6
7
8
10wt%Cu/HAP
10wt%Cu/HAP
10wt%Cu/MgO
O
O
O
O
2
2
2
2
NH
NH
NH
NH
4
HCO
HCO
HCO
HCO
3
3
3
3
/1.5
/1.5
/1.5
/1.5
DMF
H2O
DMF
DMF
88
0
4
58 to increase with increase in Cu loading up to a 10wt% and
4
further increase leads to lower yields (Table 3). The decrease
10wt%Cu/Mg-
LaO
4
60
in the catalytic activity is due to agglomeration of copper
55 particles at higher loadings. The pure HAP is found to be
inactive for the nitrile formation under the similar
9
10wt%Cu/LaO
O
O
O
O
O
O
O
O
N
O
O
O
2
2
2
2
2
2
2
2
2
2
2
2
NH
NH
NH
NH
NH
NH
NH
NH
NH
NH
4
HCO
HCO
HCO
3
3
3
/1.5
/1.5
/1.5
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1
1
1
0
1
2
10wt%Pd/HAP
HAP
4
72
experimental conditions (Table 3 entry 1). However, formation
4
0
of nitriles is marginally low over 12.5wt%Cu/HAP catalyst.
10wt%Cu/HAP
10wt%Cu/HAP
10wt%Cu/HAP
10wt%Cu/HAP
10wt%Cu/HAP
10wt%Cu/HAP
3
(aq.)/1.5
0
These results thus suggest a 10wt%Cu loading is an optimum
71 composition, which demonstrated higher yields compared to
48 other loadings on HAP.
b
1
3
4
HCO
HCO
HCO
HCO
HCO
HCO
3
3
3
3
3
3
/1.5
/1.5
/1.5
/1.5
/1.5
/1.5
c
1
4
4
d
e
1
1
5
4
52
30
20
10
28
40
Table 3: Influence of copper loading on HAP for the cyanation reaction
6
4
Entry
Catalyst
Oxidant
N
Solvent Yield
(%)
1
7
4
source/mmol
1
2
3
4
5
6
7
8
HAP
O
O
O
O
O
2
2
2
2
2
NH
NH
NH
NH
NH
4
HCO
HCO
HCO
HCO
HCO
3
3
3
3
3
/1
/1
/1
/1
/1
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
0
1
1
2
8
9
0
10wt%Cu/Al
2
O
3
4
2.5wt%Cu/HAP
5wt%Cu/HAP
7.5wt%Cu/HAP
10wt%Cu/HAP
12.5wt%Cu/HAP
10wt%Cu/HAP
10wt%Cu/HAP
4
24
37
52
78
81
85
88
10wt%Ni/HAP
10wt%Ru/HAP
NH
NH
4
HCO
3
/1.5
4
HCO
3
/1.5
4
4
a
Reaction Conditions: 150 mg of 10wt%Cu/HAP catalyst, 2-Phenylpyridine (0.5
b
4
2
mmol), N source (1.5 mmol), Solvent (2 mL), Oxidant (O balloon), 140 °C, 18h;
c
d
e
Reaction at 120 °C ; Reaction at 100 °C; 12h at 140 °C; 6 h at 140 °C.
O2
4
NH HCO /1
3
3
O
O
2
2
NH
NH HCO
-oxidant, DMF-2mL.
4
HCO
/2
An improvement in the product yield is observed when DMSO
is replaced with DMF (Table 2, enrty 2). Using various oxidants
4
3
/1.5
such as oxygen, Ag
2
O, and TBHP; oxygen has been identified as
Scale: 0.5mmol 2-phenylpyridine, O
2
suitable oxidant for the reaction (Table 2, entries 3, 4). An
improvement in the product yield is observed while the
Substrate Scope
4 3
amount of NH HCO is increased from 1 to 1.5 mmol (Table 2, Based on the optimized conditions, several substrates are
entry 5). When the solvent DMF is replaced with water the examined for the C-H bond cyanation using DMF (as solvent
reaction is not occurred (Table 2, entry 6). From this it can be and “C” source as well) with NH HCO (1.5 mmol) and O as
4
3
2
concluded that the presence of DMF is necessary to get the oxidant at a reaction temperature of 140 °C (Table 2).Using 4-
product in high yields. The use of other heterogeneous copper methyl 2-phenylpyridine, the corresponding mono cyano
based catalysts such as Cu(II)/Mg-LaO, Cu(II)/MgO and derivative is obtained with 72% yield (2b). To some extent, the
2 3
Cu(II)/La O exhibited inferior activity when compared to the reaction is sensitive to methyl substitution on the meta
Cu(II)/HAP catalyst (Table 2, entries 7, 8 and 9). It is interesting position of the 2-phenyl ring (2c), delivering the product in a
to note that the other base and non-base metals such as Ni, Pd slightly lower yield than its para counterpart (2b and 2c).
and Ru supported on HAP catalysts demonstrated lower Whereas the para substituted methoxy group has offered 67%
activity when compared to Cu/HAP catalyst (Table 2, entries yield (2d). In contrast, the halo substituted 4-fluoro, 4-chloro
10, 19, 20). The support alone did not show any activity (Table and 4-bromo analogues showed yields in the range of 60 to
2
entry 11). It has been observed that NH
4
HCO
3
is a suitable 68% (2e, 2f and 2g). The other functional groups such as –Ph, –
4
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CN and –CF
corresponding cyano derivatives of 2-phenylpyridine which major role of CuO species dispersed on HAP for the cyanation
showed reasonably good yields (2h, 2i and 2j). Remarkably, 1- reaction (Table 2, entry 11). From the N O titration data, it can
naphthyl and 2-naphthyl derivatives of pyridine also furnished be inferred that higher the Cu metal surface area, the
3
are also under gone cyanation reaction with the process. Thus, indicating the inert behavior of HAP and the
2
2
-
the cyanation product with moderate yields (2k and 2l). cyanation activity was high. We believe that the basic sites (O
Interestingly, isoquinoline and quinoline could act as directing ) present on copper species are responsible for the cyanation
groups, delivering the corresponding aryl nitriles with about reaction. These sites are reversibly generated in the presence
6
1% and 63% yields, respectively (2m and 2n). Gratifyingly, of O
benzo[h]quinoline also demonstrated good efficiency in the between Cu metal surface area and the formation of 2-
current cyanation reaction and produced the corresponding phenylpyridine (Figure S1). The CO TPD patterns of 10wt%Cu
cyanation product with 57% yield (2o). supported on Al , MgO and MgLaO samples are presented in
Figure S2 and their CO uptakes are reported in Table S5. It
shows that higher CO2 uptake is observed over
0wt%Cu/MgLaO when compared to 10wt%Cu/HAP sample.
The 10wt%Cu/Al O and 10wt%Cu/MgLaO both showed very
2
. It is also observed that there is a direct correlation
2
2 3
O
2
a
1
2
3
strong CO desorption peak above 650 °C which is attributed
2
to very strong basic sites. However, the overall CO uptake was
2
very low on 10wt%Cu/Al O compared to other samples. In the
2
3
comparative analysis the 10wt%Cu/HAP sample demonstrated
more number of strong basic sites than the other samples. The
normalized rate of 2-(pyridin-2-yl)benzonitrile over
-
1
-1
1
0wt%Cu/Al O catalyst is found to be 134
µ
which is much lower than on 10wt%Cu/HAP that showed ca.
mol (gCu) h ,
2
3
-1
-1
1
184
µmol (gCu) h . Whereas both the 10wt%Cu supported
on MgO and MgLaO samples exhibited more or less similar
-1
-1
rate 780 and 807
µ
mol (gCu)
h
respectively. Under the
reaction conditions adopted, HAP seems to be a suitable
support for Cu in the cyanation of arenes when compared to
1
4 3
0wt%Cu/HAP catalyzed cyanation of pyridyl arenes with DMF and NH HCO
Cu/MgO and Cu/MgLaO. From the CO desorption patterns
2
and the cyanation activity data; we believe that moderate to
strong basic sites present on the catalyst surface are effective
Plausible reaction mechanism
for the C-H bond activation of arenes.
Based on the
experimental results and in conjugation with earlier reports, a
plausible reaction mechanism is proposed and reported in
4
9
scheme 2. In the first step; active sites on Cu particle activate
the ortho C-H bond of 2-phenylpyridine to form (I). In the
-
second step; ligand exchange of CN generates the
intermediate (II), which would occur in the presence of DMF
and NH HCO . Finally, the intermediate (II) undergoes
4
3
reductive elimination to produce the desired product and Cu(I)
species, which subsequently re-oxidized to Cu(II) in the
presence of O (a green oxidant).
2
Catalyst activity studies
A 10 mL round bottom flask was charged with 2-
Phenylpyridine (77 mg, 0.5 mmol), Cu/HAP (150 mg), NH
4 3
HCO
(
1.5 mmol), DMF (2 mL) and O as oxidizing agent. The round
2
bottom flask was kept stirring at 140 °C. After 18h of run the
reaction was monitored by TLC, 5 mL of ethyl acetate was
added to the reaction mixture. The catalyst was separated by
simple centrifugation and the reaction mixture was treated
with brine solution (10 mL). The organic layer was separated
and the aqueous layer was back extracted with ethyl acetate
Scheme 2: Plausible reaction mechanism of Cu(II)/HAP catalysed synthesis of aryl
nitrile.
(
3×5 mL). The combined ethyl acetate extract was dried with
No reaction was occurred on HAP, although the pure HAP
-1
anhydrous Na SO and it was concentrated under reduced
2
4
possesses basic sites ca. 173 µmol g , indicating that basic
sites present on the support have no role on the cyanation
pressure. The pure product was isolated by flash column
chromatography on silica gel using ethyl acetate–hexane (10%)
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ARTICLE
Journal Name
as an eluent (pale yellow oil, 88% yield). The catalyst was conditions. The catalyst was recycled and used for four
washed with distilled water for several times then dried in an recycles that showed consistent activity and selectivity.
oven at 100°C and used for the next cycle. Following the
similar procedure the cyanation reaction was tested for 4
Acknowledgements
recycles.
The authors Venu and Vishali thank UGC for the award of
fellowship. AV, JB thanks DST New Delhi for funding under
Indo-Australia through AISRF program.
Recyclability studies
The recyclability of the catalyst is examined using 2-phenyl
4 3
pyridine, NH HCO and DMF at 140 °C, which emphasized that
the catalyst can be used for four consecutive cycles with
consistent yields. In the recyclability process, catalyst is References
recovered by a simple centrifugation. The recovered catalyst is
washed with distilled water, air-dried and used directly for the
1
(a) A. J Fatiadi S. Patai and Z. Rappaport Preparation and
next cycle without any further purification. The ICP-OES
analysis of fresh and used 10wt%Cu(II)/HAP showed 9.8% and
Synthetic Applications of Cyano Compounds, ed., Wiley,
New York, 1983; (b) R. C. Larock, Comprehensive Organic
Transformations, VCH, New York, 1989; (c) A. Kleemann, J.
Engel, B. Kutscher and D. Reichert, Pharmaceutical
9
.6% respectively. The XPS analysis of the fresh and used
0wt%Cu/HAP catalysts further confirmed that there is no
1
Substances: Synthesis, Patents, Applications, Thieme,
Stuttgart, Germany, 4 edn, 2001; (d) J. S. Miller and J. L.
Manson, Acc. Chem. Res., 2001, 34, 563-570.
(a) T. Sandmeyer, Ber. Dtsch. Chem. Ges., 1884, 17, 2650-
th
change in chemical composition of the Cu, Ca, P and O (Table
S3) at the near surface region. The activity data demonstrated
that the catalyst can be reused for four consecutive cycles
without loss of activity. The elemental analysis revealed that
there is no leaching of Cu from the HAP surface suggesting the
robust nature of Cu/HAP for the cyanation of aryl compounds.
2
3
2
1
2
653; (b) T. Sandmeyer, Ber. Dtsch. Chem. Ges., 1885, 18,
492-1496; (c) H. H. Hodgson, Chem. Rev., 1947, 40, 251-
77; (d) C. Galli, Chem. Rev., 1988, 88, 765-792; (e) K. W.
Rosenmund and E. Struck, Ber. Dtsch. Chem. Ges., 1919, 52
749-1756; (f) J. V. Braun and G. Manz, J. Liebigs, Ann.
Chem., 1931, 488, 111-126
,
1
(a) K. Ishihara, Y. Furuya and H. Yamamoto, Angew. Chem.,
Int. Ed., 2002, 41, 2983-2986; (b) C. W. Kuo, J. L. Zhu, J. D.
Wu, C. M. Chu, C. F. Yao and K. S. Shia, Chem.Commun.,
2
Lett., 2002, , 2369-2371; (d) K. Yamaguchi, H. Fujiwara, Y.
007, 301-303; (c) E. Choi, C. Lee, Y. Na and S. Chang, Org.
4
Ogasawara, M. Kotani and N. Mizuno, Angew. Chem., Int.
Ed., 2007, 46, 3922-3925; (e) T. Oishi, K. Yamaguchi and N.
Mizuno, Angew. Chem., Int. Ed., 2009, 48, 6286-6288.
4
(a) P. Anbarasan, T. Schareina and M. Beller, Chem. Soc. Rev.,
011,40, 5049-5067; (b) S. I. Murahashi, Synthesis of Nitriles
2
with Retention of the Cyano Group; Science of Synthesis;
Georg Thieme: Stuttgart, 2004; 345.
J. Lindley, Tetrahedron., 1984, 40, 1433-1456.
5
6
R. G. R. Bacon and H. A. O. Hill, J. Chem. Soc., 1964, 1097-
1
Figure 6: Recyclability test over 10wt%CuO/HAP catalyst.
107.
J. V. Braun and G. Manz, Ann. Chem., 1931, 488, 170-196.
K. W. Rosenmund and E. Struck, Chem. Ber., 1919, 52, 1749-
7
8
1
756.
Conclusions
9
1
1
G. P. Ellis and T. M. Romney-Alexander, Chem. Rev., 1987,
87, 779-794
I. P. Beletskaya, A. S. Sigeev, A. S. Peregudov and P.V.
Petrovskii, J. Organomet. Chem., 2004, 689, 3810-3812.
M. Sundermeier, A. Zapf, M. Beller and J. Sans, Tetrahedron
Lett., 2001, 42, 6707-6710.
5 4 3
The Ca (PO ) OH has been identified as a suitable support for
0
1
Cu in the C-H bond activation for the cyanation of hetero aryl
compounds. The CuO supported on hydroxyapatite is active
4 3
for the generation o ‘CN’ from a mixture of NH HCO and
dimethylformamide. The basic sites on hydroxyapatite have no 12 J. Zanon, A. Klapars and S. L. Buchwald, J. Am. Chem. Soc.,
role on the catalytic activity on the contrary the basic sites
contributed from copper surface are responsible for the
cyanation reaction. A direct correlation between Cu metal
surface area and cyanation activity is observed. An optimum
2003, 125, 2890-2891.
1
1
3
4
B. A. Anderson, E. C. Bell, F. O. Ginah, N. K. Harn, L. M. Pagh
and J. P. J. Wepsiec, Org. Chem., 1998, 63, 8224-8228.
M. Sundermeier, S. Mutyala, A. Zapf, A. Spannenberg and M.
Beller, J. Organomet.Chem., 2003, 684, 50-55.
copper loading is established (10wt%) under the experimental 15 N. Chatani and T. Hanafusa, J. Org. Chem., 1986, 51, 4714-
conditions adopted. In the comparative analysis the
0wt%Cu/Ca (PO OH demonstrated better yields than the
noble metal loaded (Ru and/or Pd) Ca (PO OH catalysts. We
4716.
H. E. Zieger and S. Wo, J. Org. Chem., 1994, 59, 3838-3840.
H. R. Chobanian, B. P. Fors and L. S. Lin, Tetrahedron Lett.,
1
1
6
7
1
5
4 3
)
5
4 3
)
2
006, 47, 3303-3305.
developed a cheaper base metal catalyst i.e. Cu for the safe
cyanation of hetero aryl compounds under mild reaction
1
1
8
9
R. S. Jensen, A. S. Gajare, K. Toyota, M. Yoshifujia and F.
Ozawab, Tetrahedron Lett., 2005, 46, 8645-8647.
M. Hatsuda and M. Seki, Tetrahedron., 2005, 61, 9908-9917.
6
| J. Name., 2016, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 7 of 8
Cat Pa ll ey as si es dS oc ni eo nt ca ed j &u s Tt me ca hr gn i on sl ogy
View Article Online
DOI: 10.1039/C6CY01536K
Journal Name
ARTICLE
2
0
1
A. Littke, M. Soumeillant, R. F. Kaltenbach, R. J. Cherney, C. 49 A. Modak, J. Mondal and A. Bhaumik, Green Chem., 2012, 14
,
M. Tarby and S. Kiau, Org. Lett., 2007,
K. M. Marcantonio, L. F. Frey, Y. Liu, Y. Chen, J. Strine, B.
Phenix, D. J. Wallace and C. Y. Chen, Org. Lett., 2004,
723-3725.
T. Schareina, A. Zapf and M. Beller, Tetrahedron Lett., 2005,
, 2585-2588.
9
, 1711-1714.
2840-2855.
2
6,
3
22
23
24
4
6
X. Chen, X.-S. Hao, C. E. Goodhue and J.-Q. Yu, J. Am. Chem.
Soc., 2006, 128, 6790- 6791.
S. Kamijo, T. Hoshikawa and M. Inoue, Org. Lett., 2011, 13
928-5931.
S. Zheng, C. Yu and Z. Shen, Org. Lett., 2012, 14, 3644-3637.
S. Xu, X. Huang, X. Hong and B. Xu, Org. Lett., 2012, 14, 4614-
617.
X. Hong, H. Wang, G. Qian, Q. Tan and B. Xu, J. Org. Chem.,
014, 79, 3228-3237.
J. Jin, Q. Wen, P. Lu and Y. Wang, Chem. Commun., 2012, 48
933-9935.
,
5
2
2
5
6
4
27
28
29
30
31
32
33
34
35
36
2
,
9
R. J. Song, J. C. Wu, Y. Liu, G. B. Deng, C. Y. Wu, W. T. Wei and
J. H. Li, Synlett., 2012, 2491-2496.
C. Pan, H. Jin, P. Xu, X. Liu, Y. Cheng and C. Zhu, J. Org.
Chem., 2013, 78, 9494-9498.
X. Kou, M. Zhao, X. Qiao, Y. Zhu, X. Tong and Z. Shen, Chem.
Eur. J., 2013, 19
H. Xu, P.-T. Liu, Y.-H. Li and F.-S. Han, Org. Lett., 2013, 15
354-3357.
, 16880-16886.
,
3
T. J. Gong, B. Xiao, W. M. Cheng, W. Su, J. Xu, Z. J. Liu, L. Liu
and Y. Fu, J. Am. Chem. Soc., 2013, 135, 10630-10633.
M. Chaitanya, D. Yadagiri and P. Anbarasan, Org. Lett., 2013,
1
5
, 4960-4963.
Y. Yang and S. L. Buchwald, Angew. Chem., Int. Ed., 2014, 53
677-8681.
(a) J. Kim and S. Chang, J. Am. Chem. Soc., 2010, 132, 10272-
,
8
1
3
0274; (b) J. Kim, H. Kim and S. Chang, Org. Lett., 2012, 14,
924-3927; (c) J. Kim, J. Choi, K. Shin and S.Chang, J. Am.
Chem. Soc., 2012, 134, 2528-2531; (d) Z. Wang and S. Chang,
Org. Lett., 2013, 15, 1990-1993; (e) A. B. Pawar and S. Chang,
Chem. Commun., 2014, 50, 448-450; (f ) J. Kim, H. J. Kim and
S. Chang, Eur. J. Org. Chem., 2013, 3201-3213; (g) J. Kim, H. J.
Kim and S. Chang, Angew. Chem., Int. Ed., 2012, 51, 11948-
1
1959.
(a) G. Zhang, X. Ren, J. Chen, M. Hu and J. Cheng, Org. Lett.,
011, 13, 5004-5007; (b) X. Ren, J. Chen, F. Chen and J.
37
2
Cheng, Chem. Commun., 2011, 47, 6725-6727.
38
39
40
41
R. Kishore, J. Yadav, B. Venu, A. Venugopal and M. L.
Kantam., New J. Chem., 2015, 39, 5259-5264.
M. Zahmakıran, Y. Tonbulz and S. Ozkar, Chem. Commun.,
2
010, 46, 4788–4790.
C. M. Ho, W. Y. Yu and C. M. Che, Angew. Chem., Int. Ed.,
004, 43, 3303-3307.
2
M. Sudhakar, V. Vijay Kumar, G. Naresh, M. L. Kantam, S. K.
Bhargava and A. Venugopal, Appl. Catal. B. Environ., 2016,
1
80, 113–120.
B. Chen, J. Li, W. Dai, L. Wang and S. Gao, Green Chem.,
014, 16, 3328–3334.
A. Venugopal and M. S. Scurrell, Appl. Catal. A. Gen., 2003,
45, 137-147.
J .A. S.Bett, L .G. Christner and W. K. Hall, J. Am. Chem. Soc.,
967, 89, 5535-5541.
42
43
44
45
46
47
48
2
2
1
M. P. Reddy, A. Venugopal and M. Subrahmanyam, Water
Res., 2007, 41, 379-386.
M. P. Reddy, A. Venugopal and M. Subrahmanyam, Appl.
Catal. B. Environ., 2006, 69, 167-170.
H. Tounsi, S. Djemal, C. Petitto and G. Delahay, Appl. Catal. B.
Environ., 2011, 107,158-163.
M. C. Biesinger, L. W. M. Lau, A. R. Gerson and R. St. C.
Smart, Appl. Surf. Sci., 2010, 257, 887-898.
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Catalysis Science & Technology
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DOI: 10.1039/C6CY01536K
C–H bond cyanation of arenes using N, N-dimethylformamide and NH HCO as CN source
4
3
over hydroxyapatite supported copper catalyst
a
a
a
a
a
a
Boosa Venu , Bilakanti Vishali , Gutta Naresh , Velisoju Vijay Kumar , Medak Sudhakar , Ramineni Kishore ,
b
b
a,
Jorge Beltramini , Muxina Konarova and Akula Venugopal *
a
Catalysis Laboratory, Inorganic and Physical Chemistry Division, CSIR – Indian Institute of
Chemical Technology, Tarnaka, Hyderabad – 500007, Telangana, India. Tel. +91-40-
2
7193165; Fax: +91-40-27160921; *Corresponding author email: akula@iict.res.in
NANOMAC Department, The University of Queensland, Brisbane, 4072, Queensland,
b
Australia.
Graphical abstract
5 4 3
Copper dispersed on Ca (PO ) OH has been identified as an excellent heterogeneous catalyst for the
in situ generation of ‘CN’ from NH HCO and N,N-dimethylformamide, in the C-H bond activation
4
3
of 2-phenylpyridine. A direct correlation between Cu metal surface area and the cyanation activity is
established.