Scope and limitation of propylene carbonate as a sustainable solvent in the Suzuki-Miyaura reaction

Article abstract of DOI:10.1039/c9ra07044c

The Suzuki-Miyaura reaction is one of the most used transformations in drug research. Thus making this reaction more sustainable is of considerable current interest. Here we show that propylene carbonate (PC) can be used as a solvent for the Suzuki-Miyaura reaction. PC is one of the greenest solvents since it is synthesized under green conditions by the use of carbon dioxide in the air. All reactions proceeded well and good or excellent yields were observed for the biaryl products. Nonetheless in the case of pyridazinones, 2-hydroxypropyl- chain containing side-products were observed. Importantly, this fact allowed the isolation of several novel compounds which were generated under prominently green conditions.

Full text of DOI:10.1039/c9ra07044c

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Scope and limitation of propylene carbonate as
a sustainable solvent in the Suzuki–Miyaura
reaction†
Cite this: RSC Adv., 2019, 9, 37818
b
Andrea Czompa,a Balazs Laszlo Pasztor,a Jennifer Alizadeh Sahar,a Zoltan Mucsi,
´
´
´
´
´
ac
Dora Bogdan,ac Krisztina Ludanyi,d Zoltan Vargae and Istvan M. Mandity
*
´
´
´
´
´
´
The Suzuki–Miyaura reaction is one of the most used transformations in drug research. Thus making this
reaction more sustainable is of considerable current interest. Here we show that propylene carbonate
(PC) can be used as a solvent for the Suzuki–Miyaura reaction. PC is one of the greenest solvents since it
is synthesized under green conditions by the use of carbon dioxide in the air. All reactions proceeded
well and good or excellent yields were observed for the biaryl products. Nonetheless in the case of
pyridazinones, 2-hydroxypropyl- chain containing side-products were observed. Importantly, this fact
allowed the isolation of several novel compounds which were generated under prominently green
conditions.
Received 3rd September 2019
Accepted 29th October 2019
DOI: 10.1039/c9ra07044c
rsc.li/rsc-advances
propylene carbonate (PC) and various polar and nonpolar
solvents on palladium-catalyzed Suzuki–Miyaura coupling of
Introduction
chloroaryl triates. They highlighted the similar selectivity of
the solvents and the synthetic value of it.21 PC was used with no
loss of enantioselectivity in an iridium- and rhodium-
phosphite/oxazoline catalytic system catalysed asymmetric
hydrogenation of functionalized cyclic b-enamines,22 and in
cathodic reduction of aryl halides, considered for its high
dielectric permittivity.23 PC was used in an aminophosphine
palladium pincer-catalyzed carbonylative Sonogashira reaction
with 10À4 mol%, while the Suzuki–Miyaura cross-coupling
reaction was carried out at 10À6 mol%.24 Nonetheless, Pd/C
catalysed phenoxycarbonylation of aryl iodide was carried out
using N-formylsaccharin as a CO surrogate in PC as a sustain-
able solvent.25 Heck reaction was carried in cyclic carbonates as
greener solvents, offering effective alternative to traditionally
used dipolar aprotic solvents.26 Nanostructured palladium
clusters catalysed also Heck reaction and were stable in
The Suzuki–Miyaura reaction is the palladium-catalysed cross-
coupling reaction of organoboranes with organic halides, tri-
ates or peruorinated sulfonates and proceeds with high
stereo- and regioselectivity.1 Recent developments with respect
to catalysts and methods have broadened the possible appli-
cations enormously, that is, the scope of the reaction partners is
not restricted to aryls, but includes alkyls, alkenyls and alkynyls
too.2,3 Usually, the boronic acid is activated by a base and the
reaction is run in a polar aprotic solvent, ionic liquid or water.4
At room temperature, the reaction takes place with low yield;
therefore, the use of special catalyst might be required5 or
increased temperature and pressure are needed.6
Several efforts were taken to carry out Suzuki–Miyaura and
further cross coupling reactions under green and sustainable
conditions.7–20 Reeves and co-workers studied the effects of
propylene carbonate even at 140–155 C.27
ꢀ
A recent article28 reports that nanoparticles formed from
inexpensive FeCl3 naturally contains parts-per-million (ppm)
levels of Pd and can catalyse Suzuki–Miyaura reaction in water.
There is also a nickel-catalysed, but base-free Suzuki–Miyaura
reaction of carboxylic acid uorides29 and we can found
a heterogeneous and ligand-free Suzuki–Miyaura reaction
accomplished with the use of a palladium catalyst supported on
a double-structure amphiphilic polymer composite.30 Interest-
ingly, a heterogeneous single-atom palladium preparation
anchored on exfoliated graphitic carbon nitride was used in
aDepartment of Organic Chemistry, Faculty of Pharmacy, Semmelweis University,
}
Hogyes Endre u. 7, H-1092 Budapest, Hungary. E-mail: mandity.istvan@pharma.
semmelweis-univ.hu; mandity.istvan@ttk.mta.hu
b
}
´
Femtonics Ltd, Tuzolto u. 59, H-1094 Budapest, Hungary
c
¨
MTA TTK Lendulet Articial Transporter Research Group, Institute of Materials and
Environmental Chemistry, Research Center for Natural Sciences, Hungarian
´
Academy of Sciences, Magyar Tudosok krt. 2, H-1117 Budapest, Hungary
d
}
Department of Pharmaceutics, Semmelweis University, Hogyes Endre u. 7, H-1092
Budapest, Hungary
eInstitute of Materials and Environmental Chemistry, Research Center for Natural
´
Sciences, Hungarian Academy of Sciences, Magyar Tudosok krt. 2, H-1117 Budapest,
Hungary
a
homogenous systems for Suzuki coupling.31 In 2018,
† Electronic supplementary information (ESI) available: General experimental
researchers from the Pzer company published an article32
about the use of an automated ow-based synthesis platform,
set-up
experimental
procedures
including
characterization
data,
chromatograms, 1H and 13C NMR spectra. See DOI: 10.1039/c9ra07044c
37818 | RSC Adv., 2019, 9, 37818–37824
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
that integrates both rapid nanomole-scale reaction screening in lithium–metal batteries was studied in order to explore the
and micromole-scale synthesis in Suzuki–Miyaura coupling at next-generation high-energy lithium–sulfur and lithium–air
elevated temperature. The continuous-ow technology was batteries.50 PC can increase optoelectronic properties, photo-
utilized for several cross coupling reactions too.11,33–38
Small and homogenous palladium particules (4–6 nm) were perovskite solar cells against humidity, light and heat.51
introduced in multi-walled carbon nanotubes used for selective Herein we show the use of PC as prominent green solvent for
voltaic parameters and environmental stability of efficient
hydrogenation of cinnamaldehyde,39 while palladium–nickel the Suzuki–Miyaura reaction. We observed the limitation of PC
and palladium–silver nanoparticles supported on carbon as solvent, since nucleophiles can open the ring and 2-hydrox-
exhibited high activity toward the glycerol electrooxidation in ypropylation occurs. Nonetheless, this side-reaction allowed us
alkaline medium.40 Glycerol electrooxidation was achieved also the isolation of several novel compounds, thus, PC can be
on active self-supported Pd1Snx nanoparticles, when the modi- treated as a prominently green 2-hydroxypropylation reagent.
cation of palladium by tin species led to suppress the disso-
ciative adsorption process of glycerol.41 de Souza and co-workers
published an article describing the resolution of amines.42 They
immobilized lipase on functionalized Pd–SiO2 nanoparticles
and this new simplied Pd-lipase hybrid biocatalysts showed
immobilization efficiencies of around 80% when containing 1–
10% of Pd. Numerous studies focused on the bacterial synthesis
of Pd-nanoparticles (bio-Pd NPs) by uptake of Pd(II) ions and
their enzymatically-mediated reduction to Pd(0). One of them
deal with microwave-injured Pd(II)-treated cells (and non MW-
treated controls) which were contacted with H2 to promote
Pd(II) reduction.43
Results and discussion
As mentioned, two different heating ways (oil bath and MW
irradiation) were applied in the Suzuki–Miyaura reaction with 2-
iodopyridine (2), 4-iodopyridine (3) and 6-iodopyridazin-3(2H)-
one (4) as starting materials. The rst two are commercial
products, while the last one was synthesized in two steps from
commercially available 3,6-dichloropyridazine. The chlorine
atoms were substituted with iodine52,53 in the presence of aq. HI
followed by alkaline hydrolysis of the formed 3,6-diiodopyr-
idazine54,55 in order to obtain 6-iodopyridazin-3(2H)-on (4). The
heterocyclic substrates were reacted with four different boronic
acids (Scheme 2), namely, 2-naphthylboronic acid (5), phenyl-
boronic acid (6), 4-biphenylboronic acid (7) and 4-uo-
rophenylboronic acid (8).
The Suzuki–Miyaura reaction was investigated under tradi-
tional oil-heating and microwave conditions using propylene
carbonate (PC, 1, Scheme 1) as a green solvent. Three hetero-
cyclic substrates: 2-iodopyridine (2), 4-iodopyridine (3) and 6-
iodopyridazin-3(2H)-one (4), were used as coupling partners.
The use of PC allows to increase the temperature of the
Suzuki reaction (usually lower or around 100 ꢀC) and meantime,
decrease the reaction time. Propylene carbonate (1) is among
the green solvents44 in the GlaxoSmithKline solvent sustain-
ability guide. It is known as a carbon-dioxide neutral solvent45
and can be obtained from propylene oxide and carbon dioxide.46
The cycloaddition of CO2 and propylene oxide catalysed by NiO-
modied TiO2 nanoparticles with tetrabutylammonium iodide
used as co-catalyst, under solvent free conditions was achieved
in excellent yield47 and the green synthesis of PC was also
published.48 In this last paper, the authors used microwave in
order to intensify the lipase catalysed transesterication of 1,2-
propanediol with dimethyl carbonate in non-aqueous media
and observed that microwave irradiation not only increase the
reaction rate, but also improved the thermal stability of the
enzyme. This “green” solvent is a good electrolyte during
lithium-ion intercalation and de-intercalation in lattice
contraction/recovery of W18O49 nanowires used as electro-
chromic actuator.49 The molecular dynamics of lithium and PC
Reactions were carried out in the presence of tetrakis(-
triphenylphosphane)palladium(0) as catalyst and disodium
carbonate as base. The Suzuki–Miyaura reaction of 5 with
iodopyridines is shown on Scheme 3, while with iodopyridazin-
3(2H)-one 4 is depicted on Scheme 4.
Scheme 2 Structure of boronic acids.
Scheme 1 Structure of solvent and substrates.
Scheme 3 Synthesis of 2- and 4-(naphthalen-2-yl)pyridine.
RSC Adv., 2019, 9, 37818–37824 | 37819
This journal is © The Royal Society of Chemistry 2019

View Article Online
RSC Advances
Paper
By traditional oil-bath heating, reactions were run until full
conversion of substrates monitored by TLC at 254 nm. Under
microwave irradiation, in turn, in all cases, the reaction time
was adjusted to 1 hour, but the same temperature (130 ꢀC) was
utilized. The oil-heating experiments of 2-iodopyridine (2) and
4-iodopyridine (3) were performed in the dark (ask covered by
tinfoil), because they are light and air sensitive (Schemes 3 and
5). In the case of the third substrate: 6-iodopyridazin-3(2H)-one
(4), we did not observe stability problems of the starting mate-
rial, thus there was no need to carry out the reaction in the dark.
However, side-products were formed (Schemes 4 and 6; see
further discussion).
The Suzuki–Miyaura cross-coupling reactions were carried
out under the above-mentioned conditions. On the basis of the
necessary reaction times shown in Table 1, we can state that: 4-
uorophenylboronic acid (8) has higher reactivity, while phe-
nylboronic acid (6) is less reactive than all other boronic acids.
Furthermore, 2-naphthylboronic acid (5) and 4-biphe-
nylboronic acid (7) show similar reactivity. The results suggest
that the reactivity of aromatic boronic acid is not dramatically
inuenced by the aromatic substituent. That is the reaction
time of compounds 5 and 7 with a fused and isolated aromatic
ring, respectively, is very similar. There can be found several
data in the literature, such as HPLC of phenylboronic acid56 (6)
and LC-MS data of 6-phenylpyridazin-3(2H)-one57 (18a). No
information is available, however, for our new products: 11b,
19b and 20b. We measured the maximum absorbance (lmax) of
the starting materials and all products by HPLC-UV method and
the retention time of all received products at 254 nm (ESI†).
The results of our experiments are summarized in Table 2.
All yields are acceptable or excellent and, in general, the yields
of the isolated compounds are in good accordance with those
results obtained by HPLC analysis of the raw products.
Scheme 4 Suzuki–Miyaura reaction of 6-iodopyridazin-3(2H)-one
with 2-naphthaleneboronic acid.
In case of the reaction 5 with 4 a side-product was observed
of which is depicted in Scheme 4.
The Suzuki–Miyaura reaction of phenylboronic acids 6, 7,
and 8 with iodopyridines 2 and 3 is shown in Scheme 5.
In case of the Suzuki–Miyaura reaction of iodocompound 4
with phenylboronic acids 6, 7 and 8 again the side-product was
formed.
Scheme 5 Suzuki–Miyaura reaction of iodopyridines 2 and 3 with
phenylboronic acid (6), 4-biphenylboronic acid (7) and 4-fluo-
robenzeneboronic acid (8).General method: 1 mmol hetrocyclic Scheme 6 Suzuki–Miyaura reaction of 6-iodopyridazin-3(2H)-one (4)
substrates (2, 3 or 4), 1.25 mmol boronic acids (5, 6, 7 or 8), 0.05 mmol with phenylboronic acid (6), 4-biphenylboronic acid (7) and 4-fluo-
Pd(PPh3)4, 5 mL PC (1) and 2 mL 0.5 M Na2CO3 heated at 130 ꢀC.
robenzeneboronic acid (8).
37820 | RSC Adv., 2019, 9, 37818–37824
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
According to the necessary reaction times to attain total
RSC Advances
Both 2-(naphthalen-2-yl)pyridine72,73 (9) and 2-(biphenyl-4-yl)
conversion shown in Table 1, 2-iodopyridine (2) had higher pyridine74,75 (14) could be obtained in excellent average yields in
reactivity compared to 4-iodopyridine (3) in the Suzuki–Miyaura oil bath: 91% in 5 h (9) and 92% in 3 h (14). Similar tendency
reaction with boronic acids 5, 6 and 7. The lowest yield was can be observed for reactions conducted under microwave
found in the reaction of 2-iodopyridine derivatives with 4-uo- irradiation, but in shorter reactions of 1 h: 91% for 9 and 95%
rophenylboronic acid both under conventional heating and for 14. Interestingly, compound 1376–78 was obtained in the
under microwave conditions (8). Aer 3 h reaction time, lowest yield of 47% by oil heating; however, this increased to an
product 1658–60 was formed only in an acceptable average yield of average yield of 72% under MW conditions.
51% by oil heating and 57% average yield under MW condi-
In the Suzuki–Miyaura reaction of 6-iodopyridazin-3(2H)-one
tions. 4-(4-Fluorophenyl)pyridine61–63 (17) was obtained with (4), beside the expected products (11a, 18a, 19a and 20a) four
a 75% average yield by traditional heating in 1 h and 82% other compounds (11b, 18b, 19b and 20b) were also formed.
average yield under microwave irradiation. From this results we Furthermore, these side-products seem to be formed in 1 : 1
conclude that, in the same reaction time, reactions conducted proportion with the expected ones, like in the reaction of 4 with
under microwave irradiation afford higher yields, than those for 5 under conventionally heating or with 6 under microwave
oil-heating experiments. One explanation can be the inhomo- irradiation (see related data in Table 2). Compounds 11a,79,80
genity of temperature in the oil bath, although the oil was well- 18a79,81,82 and 18b83,84 are known in the literature; however, side-
stirred with a stirring bar. Product 1264–66 can be obtained from product 11b is not yet published. As shown, it was obtained in
2-iodopyridine (2) and phenylboronic acid (6) in approximately a yield similar to those of the expected product 11a. The same is
65% average yield in the longest reaction (7 h, oil bath) and with true for products 18a and 18b.
66% average yield in 1 h (MW heating). Note that the use of MW
irradiation in Suzuki–Miyaura reaction allows us to save time products (19b, 20b) seem to be formed in higher yields than
and energy. those for the expected one (19a, 20a). We observed a 27%
In contrast, in the reaction of 7 and 8, the unexpected
4-Iodopyridine 3 in the reaction with boronic acids 5 and 7 average yield for 19a85 and a 59% average yield both under oil
gave the corresponding products in very high yields. Product bath and MW heating conditions for 19b. A similar tendency
1067–69 was obtained with 84% average yield in 3 h by oil heating, was observed in the reaction of 4 with 4-uorophenylboronic
and 86% average yield under MW conditions. Because of its acid (8). Product 20b was formed in an average yield of 53%,
reactivity, 4-biphenylboronic acid (7) gave full conversion under while only a 41% yield was measured for 20a86–88 both under
conventional oil heating in only 2 h to afford product 1570,71 microwave conditions and oil-bath heating. The structure of the
isolated with 90% average yield. An 88% average isolated yield side-products was elucidated by NMR spectroscopy and mass
was observed under MW irradiation.
spectroscopy (ESI†).
The explanation for the formation of byproducts 11b, 18b,
19b and 20b is the base-induced deprotonation of the pyr-
idazinone and opening of propylene carbonate89 ring (Scheme
7). The hydrolysis of propylene carbonate to 1,2-propylene glycol
was published by the use of a supported basic ionic liquid in
Table 1 Reaction time (in hours) to attain complete conversion by
conventional heating
a stainless steel autoclave heated to 140 C for 4 h.90
ꢀ
Reagents
5
6
7
8
We did not observe the formation of side-products in the
reaction of 2-iodopyridine (2) and 4-iodopyridine (3), because
they do not have acidic H attached to the nitrogen atom. The
2
3
4
5 h
3 h
4 h
7 h
3 h
6 h
3 h
2 h
3 h
3 h
1 h
3 h
Table 2 Obtained yields for the Suzuki–Miyaura reactions
Yield (%)
5
6
7
8
2
92% (9)a
65% (12)a
64% (12)c
65% (12)b
67% (12)c
47% (13)a
47% (13)c
74% (13)b
69% (13)c
95% (14)a
43% (16)a
89% (9)c
89% (14)c
58% (16)c
93% (9)b
97% (14)b
50% (16)b
88% (9)c
92% (14)c
63% (16)c
3
4
85% (10)a
92% (15)a
71% (17)a
82% (10)c
87% (15)c
79% (17)c
85% (10)b
91% (15)b
80% (17)b
86% (10)c
84% (15)c
84% (17)c
19% (11a) + 20% (11b)a
21% (11a) + 19% (11b)c
36% (11a) + 52% (11b)b
48% (11a) + 50% (11b)c
47% (18a) + 52% (18b)a
40% (18a) + 57% (18b)c
45% (18a) + 45% (18b)b
51% (18a) + 48% (18b)c
32% (19a) + 58% (19b)a
21% (19a) + 76% (19b)c
26% (19a) + 49% (19b)b
29% (19a) + 51% (19b)c
33% (20a) + 56% (20b)a
43% (20a) + 54% (20b)c
44% (20a) + 50% (20b)b
44% (20a) + 51% (20b)c
a
Isolated yield for the conventionally heated reaction. b Isolated yield for microwave assisted reaction. c Estimated yield from HPLC analysis and
weight of the raw products.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 37818–37824 | 37821

View Article Online
RSC Advances
Paper
Scheme 7 Reaction of PC with 6-iodopyridazin-3(2H)-one under
alkaline conditions.
Scheme 9 Reaction mechanism showing nanoparticle formation and
Suzuki-product synthesis both in homogeneous and heterogeneous
phase.92
hydrogen on the N-2 atom of 6-iodopyridazin-3(2H)-one (4) is
acidic (Scheme 7); therefore, it can easily undergo deprotona-
tion by aqueous Na2CO3 and the formed negatively charged
nucleophilic N-atom of the pyridazinone ring (22) will attack the
most electrophilic C-atom of propylene carbonate (1). Subse-
quent ring opening results in the formation of 2-(2-hydrox-
ypropyl)-6-iodopyridazin-3(2H)-one (23), which will react with
the corresponding boronic acid derivatives and give the side-
compounds. Although, Allerton and co-workers published the
alkylation of the N-2 atom of the 6-piperazinyl substituted pyr-
idazinone ring, but only with a side chain formed from ethylene
carbonate, in DMF-solution and KOH as base. Similarly, the N-
alkylation of the benzyl 4-(6-oxo-1,6-dihydropyridazin-3-yl)
piperazin-1-carboxylate with (R)- and (S)-propylene oxide was
carried out under phase transfer conditions in DCM and water,
respectively.91
In order to support our theory, we made additional experi-
ments. Starting from pyridazinone (4) we synthesized
compound (23) under 1 h MW irradiation (Scheme 7), in the
presence of the solvent (PC), base (Na2CO3), without and with
Pd(PPh3)4 as catalyst. Compound 23, an unknown product, was
obtained in good yields of 80% and 78%. On the other hand, we
performed a reaction starting from 11a, only in the presence of
propylene carbonate (1) and the base and obtained product 11b
in 67% yield (Scheme 8).
This experimental observation suggests that under similar
reaction conditions (1 h MW irradiation or 130 ꢀC, oil bath
heating) more side-product 11b can be obtained rather than the
expected Suzuki-coupled product (11a) and we propose that
compound 23 is an intermediate in all Suzuki–Miyaura reac-
tions starting from heterocyclic substrate 4. Additionally, not
only 23 can lead to the formation of 11b, however the cross-
coupled 11a can react with PC yielding 11b.
It was proposed that Pd nanoparticles are effective catalysts
for Suzuki–Miyaura reaction.92 To test the presence of nano-
particles in our reactions carried out in PC, TEM measurements
were carried out. The synthesis of 17 was used as test reactions,
and aliquots were taken at 20, 40 and 60 min. Aer an hour the
reaction is complete. The aliquots were lyophilized, the resulted
solid was dissolved in methanol, and this solution was inves-
tigated by TEM measurements. The results indicate that nano-
particles in the diameter range of 1–5 nm can be observed in the
sample at 40 and 60 min (Fig. 1).
Scheme
reaction.
8 Reaction of PC with the product of Suzuki–Miyaura
The mechanism depicting the nanoparticle formation and
the Suzuki-product synthesis both in homogeneous and
heterogeneous phase is shown in Scheme 9.
Conclusions
PC was used as prominently green solvent for the Suzuki–
Miyaura cross coupling reaction. The reaction was examined
with 3 different heterocyclic iodocompounds (2, 3, 4) with 4
different boronic acids (5, 6, 7, 8) under microwave condition
and conventional oil bath heating. In general, iodopyridines 2
and 3 reacted smoothly in the expected way providing the cross-
Fig. 1 Pd nanoparticles in the 1–5 nm diameter range found in the
reaction mixture of the synthesis of 17 after 40 (a) and 60 (b) min
reaction time.
37822 | RSC Adv., 2019, 9, 37818–37824
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
coupled product. However, 6-iodopyridazin-3(2H)-on (4) reacted 13 F. Benaskar, V. Engels, E. V. Rebrov, N. G. Patil, J. Meuldijk,
alternatively and side-product formation was observed. Never-
theless, 6-iodopyridazin-3(2H)-on (4) is the most reactive with
phenyl- (6) and 4-uorophenylboronic acid (8) (containing
P. C. Thune, P. Magusin, B. Mezari, V. Hessel, L. A. Hulshof,
E. J. M. Hensen, A. E. H. Wheatley and J. C. Schouten, Chem.–
Eur. J., 2012, 18, 1800–1810.
a single aromatic ring), while 2-iodopyridine (2) gave the best 14 N. Karbass, V. Sans, E. Garcia-Verdugo, M. I. Burguete and
yield with 2-naphthylboronic acid (5), and 4-biphenylboronic S. V. Luis, Chem. Commun., 2006, 3095–3097.
acid (7) containing two aromatic rings. 4-Iodopyridine (3) 15 M. I. Burguete, E. Garcia-Verdugo, I. Garcia-Villar, F. Gelat,
provided higher yields with boronic acids 5 and 7, and also
afforded good yield with 4-uorophenylboronic acid 8.
P. Licence, S. V. Luis and V. Sans, J. Catal., 2010, 269, 150–
160.
Despite of its high boiling point, solvent PC was found to be 16 B. Altava, M. I. Burguete, E. Garcia-Verdugo, N. Karbass,
rather reactive under our reaction conditions. This lead to the
formation of side-products in case of iodopyridazin-3(2H)-on.
S. V. Luis, A. Puzary and V. Sans, Tetrahedron Lett., 2006,
47, 2311–2314.
However, as a result of the degradation of PC, we were able to 17 L. Timbart and J. C. Cintrat, Chem.–Eur. J., 2002, 8, 1637–
synthesize new heterocyclic compounds possessing 2-hydrox- 1640.
ypropyl substituent and 11b, 19b, 20b and 23 were isolated in 18 S. Miniere and J. C. Cintrat, J. Org. Chem., 2001, 66, 7385–
good yields. Besides of the isolated novel compounds, we 7388.
demonstrated that PC can be an efficient and cost-effective 19 D. Buissonneaud and J. C. Cintrat, Tetrahedron Lett., 2006,
solvent to perform “green” Suzuki reactions by traditional oil 47, 3139–3143.
and MW heating. Importantly, considerable attention should be 20 M. Abarbri, J. L. Parrain, J. C. Cintrat and A. Duchene,
payed for the substrate selection, since nucleophiles can open Synthesis, 1996, 82–86.
the ring of PC yielding side-products with 2-hydroxypropyl side- 21 E. K. Reeves, O. R. Bauman, G. B. Mitchem and
chain.
S. R. Neufeldt, Isr. J. Chem., 2019, 59, 1–5.
´
22 M. Biosca, M. Magre, M. Coll, O. Pamies and M. Dieguez,
Adv. Synth. Catal., 2017, 359, 2801–2814.
23 V. Jouikov and J. Simonet, Electrochem. Commun., 2010, 12,
781–783.
Conflicts of interest
There are no conicts to declare.
24 P. Gautam, N. J. Tiwari and B. M. Bhanage, ACS Omega, 2019,
4, 1560–1574.
25 P. Gautam, P. Kathe and B. M. Bhanage, Green Chem., 2017,
19, 823–830.
Acknowledgements
´
´
´
Authors thank to Eva Bulyaki and Terez Kiss for the TEM
investigations.
26 H. L. Parker, J. Sherwood, A. J. Hunt and J. H. Clark, ACS
Sustainable Chem. Eng., 2014, 2, 1739–1742.
27 M. T. Reetz and G. Lohmer, Chem. Commun., 1996, 16, 1921–
1922.
Notes and references
1 N. Miyaura and A. Suzuki, Chem. Commun., 1979, 866–867.
2 A. K. Mapp and C. H. Heathcock, J. Org. Chem., 1999, 64, 23–
28 S. Handa, Y. Wang, F. Gallou and B. H. Lipshutz, Science,
2015, 349, 1087–1091.
27.
29 C. A. Malapit, J. R. Bour, C. E. Brigham and M. S. Sanford,
Nature, 2018, 563, 100–104.
30 M. Wang, H. Xue, F. Ju and H. Yang, Sci. Rep., 2017, 7, 7006–
7014.
3 G. A. Molander and F. Dehmel, J. Am. Chem. Soc., 2004, 126,
10313–10318.
4 M. Yus, I. Pastor and R. Martınez, Synthesis, 2014, 46, 2965–
´
˜
31 Z. Chen, E. Vorobyeva, S. Mitchell, E. Fako, M. A. Ortuno,
2975.
´ ´
N. Lopez, S. M. Collins, P. A. Midgley, S. Richard, G. Vile
5 C. J. Mathews, F. McLachlan, P. J. Smith and T. Welton,
Organometallics, 2003, 22, 5350–5357.
´
´
and J. Perez–Ramırez, Nat. Nanotechnol., 2018, 13, 702–707.
6 I. Nagao, M. Chatterjee and H. Kawanami, Catalysts, 2018, 8, 32 D. Perera, J. W. Tucker, S. Brahmbhatt, C. J. Helal, A. Chong,
451–459.
W. Farrell, P. Richardson and N. W. Sach, Science, 2018, 359,
429–434.
33 C. Wiles and P. Watts, Green Chem., 2014, 16, 55–62.
7 T. Schmidt and A. Kirschning, Angew. Chem., Int. Ed., 2012,
51, 1063–1066.
8 K. Mennecke and A. Kirschning, Beilstein J. Org. Chem., 2009, 34 C. Wiles and P. Watts, Chem. Commun., 2011, 47, 6512–6535.
5, No.21.
35 C. Wiles and P. Watts, Eur. J. Org. Chem., 2008, 2008, 1655–
9 K. Mennecke and A. Kirschning, Synthesis, 2008, 3267–3272.
1671.
10 E. Geist, A. Kirschning and T. Schmidt, Nat. Prod. Rep., 2014, 36 C. Wiles and P. Watts, Green Chem., 2012, 14, 38–54.
31, 441–448.
37 F. Benaskar, N. G. Patil, E. V. Rebrov, A. Ben-Abdelmoumen,
J. Meuldijk, L. A. Hulshof, V. Hessel and J. C. Schouten,
ChemSusChem, 2013, 6, 353–366.
11 N. Erdmann, Y. H. Su, B. Bosmans, V. Hessel and T. Noel,
Org. Process Res. Dev., 2016, 20, 831–835.
12 C. Bottecchia, M. Rubens, S. B. Gunnoo, V. Hessel, 38 F. Benaskar, A. Ben-Abdelmoumen, N. G. Patil, E. V. Rebrov,
A. Madder and T. Noel, Angew. Chem., Int. Ed., 2017, 56,
12702–12707.
J. Meuldijk, L. A. Hulshof, V. Hessel, U. Krtschil and
J. C. Schouten, J. Flow Chem., 2011, 1, 74–U95.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 37818–37824 | 37823

View Article Online
RSC Advances
Paper
39 J. P. Tessonnier, L. Pesant, G. Ehret, M. J. Ledoux and 66 S. M. Ghodse and V. N. Telvekar, Tetrahedron Lett., 2017, 58,
C. Pham-Huu, Appl. Catal., A, 2005, 288, 203–210. 524–526.
40 Y. Holade, C. Morais, K. Servat, T. W. Napporn and 67 S. P. Gromov and M. V. Fomina, Chem. Heterocycl. Compd.,
K. B. Kokoh, ACS Catal., 2013, 3, 2403–2411. 2004, 53, 901–905.
41 A. Zalineevaa, A. Serovb, M. Padilla, U. Martinez, 68 H. Ila and H. Junjappa, Tetrahedron, 1990, 46, 2561–2572.
K. Artyushkova, S. Baranton, C. Coutanceaua and 69 V. B. Nazarov, V. G. Avakyan, S. P. Gromov, M. V. Fomina,
P. B. Atanassov, Appl. Catal., B, 2015, 176–177, 429–435.
T. G. Vershinnikova and M. V. Almov, Chem. Heterocycl.
Compd., 2004, 53, 2525–2531.
˜
42 S. P. de Souza, R. A. C. Leao, J. F. Bassut, I. C. R. Leal,
S. Wang, Q. Ding, Y. Li, F. L. Y. Lam, R. O. M. A. de Souza 70 T. Markovic, B. N. Rocke, D. C. Blakemore, V. Mascitti and
and I. Itabaiana Jr, Tetrahedron Lett., 2017, 58, 4849–4854. M. C. Willis, Chem. Sci., 2017, 8, 4437–4442.
43 J. Gomez-Bolivar, I. P. Mikheenko, L. E. Macaskie and 71 O. Kobayashi, D. Uraguchi and T. Yamakawa, Org. Lett.,
M. L. Merroun, Nanomaterials, 2019, 9, 857. 2009, 11, 2679–2682.
44 C. M. Alder, J. D. Hayler, R. K. Henderson, A. M. Redman, 72 J. -Q. Liu, B. -Y. Hao, H. Zou, W. -H. Zhang and X. -Z. Chen,
L. Shukla, L. E. Shuster and H. F. Sneddon, Green Chem.,
2016, 18, 3879–3890.
45 P. Gautam, R. Gupta and B. M. Bhanage, Eur. J. Org. Chem.,
2017, 2017, 3431–3437.
46 N. Oncel, V. T. Kasumov, E. Sahin and M. Ulusoy, J.
Organomet. Chem., 2016, 811, 81–90.
Arkivoc, 2014, 5, 72–93.
73 L. -Y. Xi, R. -Y. Zhang, S. Liang, S. -Y. Chen and X. -Q. Yu, Org.
Lett., 2014, 16, 5269–5271.
74 T. Funaki, H. Otsuka, N. Onozawa-Komatsuzaki, K. Kasuga,
K. Sayama and H. Sugihara, J. Mater. Chem. A, 2014, 2,
15945–15951.
47 S. Kumara, D. K. Mishrab, A. J. F. N. Sobral and J. Koh, J. CO2 75 Y. Shen, J. Chen, M. Liu, J. Ding, W. Gao, X. Huang and
Util., 2019, 34, 386–394. H. Wu, Chem. Commun., 2014, 50, 4292–4295.
48 G. D. Yadav, M. P. Hude and A. D. Talpade, Chem. Eng. J., 76 B. Li, Y. Yu, P. Zhao and S. Zhang, Chem.–Asian J., 2016, 11,
2015, 281, 199–208. 3550–3556.
49 K. Li, Y. Shao, H. Yan, Z. Lu, K. J. Griffith, J. Yan, G. Wang, 77 M. Tobisu, T. Furukawa and N. Chatani, Chem. Lett., 2013,
H. Fan, J. Lu, W. Huang, B. Bao, X. Liu, C. Hou, Q. Zhang, 42, 1203–1205.
Y. Li, J. Yu and H. Wang, Nat. Commun., 2018, 9, 4798–4808. 78 G. Ranjani and R. Nagarajan, Org. Lett., 2017, 19, 3974–3977.
50 Q. Li, S. Tan, L. Li, Y. Lu and Y. He, Sci. Adv., 2017, 3, 1–9.
51 T. -H. Han, J. -W. Lee, C. Choi, S. Tan, C. Lee, Y. Zhao, Z. Dai,
79 Q. Gao, Y. Zhu, M. Lian, M. Liu, J. Yuan, G. Yin and A. Wu, J.
Org. Chem., 2012, 77, 9865–9870.
N. De Marco, S. -J. Lee, S. -H. Bae, Y. Yuan, H. M. Lee, 80 J. Druey and B. H. Ringier, Helv. Chim. Acta, 1951, 34, 195–
Y. Huang and Y. Yang, Nat. Commun., 2019, 10, 520–529.
52 WO2007048802 (A1), 2007.
53 WO2008071646 (A1), 2008.
210.
81 E. Sotelo, N. Fraiz, M. Yanez, V. Terrades, R. Laguna, E. Cano
´˜
and E. Ravina, Bioorg. Med. Chem., 2002, 10, 2873–2882.
˜
´
´
54 S. Kamiya, A. Nakamura, T. Itai, K. Koshinuma and 82 R. Salives, G. Dupas, N. Ple, G. Queguiner, A. Turck,
G. Okusa, Yakugaku Zasshi, 1966, 86, 1099–1104.
55 WO2011154677 (A1), 2011.
P. George, M. Sevrin, J. Frost, A. Almario and A. Li, J.
Comb. Chem., 2005, 7, 414–420.
56 V. F. Hawkins, M. C. Wilkinson and M. Whiting, Org. Process 83 DE2445681A1, 1976.
Res. Dev., 2008, 12, 1265–1268.
57 US20120028971 (A1), 2012.
84 AT333774B, 1976.
85 US5763440A, 1998.
58 L. Ackermann, H. K. Potukuchi, A. R. Kapdi and C. Schulzke, 86 F. Csende, Z. Szabo, G. Bernath and G. Stajer, Synthesis,
Chem.–Eur. J., 2010, 16, 3300–3303. 1995, 1240–1242.
59 A. Jakab, Z. Dalicsek, T. Holczbauer, A. Hamza, I. Papai, 87 J. D. Albright, D. B. Moran, W. B. Wright Jr, J. B. Collins,
´
´
´
Z. Finta, G. Timari and T. Soos, Eur. J. Org. Chem., 2015,
2015, 60–66.
B. Beer, A. S. Lippa and E. N. Greenblatt, J. Med. Chem.,
1981, 24, 592–600.
60 A. R. Mazzotti, M. G. Campbell, P. Tang, J. M. Murphy and 88 DE2741763 (A1), 1978.
T. Ritter, J. Am. Chem. Soc., 2013, 135, 14012–14015. 89 CN101121642 (A), 2008.
61 K. Kubota, Y. Watanabe, K. Hayama and H. Ito, J. Am. Chem. 90 L. F. Xiao, Q. F. Yue, C. G. Xia and L. W. Xu, J. Mol. Catal. A:
Soc., 2016, 138, 4338–4341.
Chem., 2008, 279, 230–234.
62 B. Li and Z. Zhang, J. Iran. Chem. Soc., 2016, 13, 637–644.
63 O. P. Shkurko, S. G. Baram and V. P. Mamaev, Chem.
Heterocycl. Com., 1983, 19, 60–65.
64 H. Hu, C. Ge, A. Zhang and L. Ding, Molecules, 2009, 14,
3153–3160.
91 C. M. N. Allerton, M. D. Andrews, J. Blagg, D. Ellis, E. Evrard,
M. P. Green, K. K.-C. Liu, G. McMurray, M. Ralph,
V. Sanderson, R. Ward and L. Wartson, Bioorg. Med. Chem.
Lett., 2009, 19, 5791–5795.
92 M. Perez-Lorenzo, J. Phys. Chem. Lett., 2012, 3, 167–174.
65 F. Haviv, R. W. DeNet, R. J. Michaels, J. D. Ratajczyk,
G. W. Carter and P. R. Young, J. Med. Chem., 1983, 26,
218–222.
37824 | RSC Adv., 2019, 9, 37818–37824
This journal is © The Royal Society of Chemistry 2019