Article catalysts Solventless Synthesis of Quaterphenyls and Solventless
Synthesis of Quaterphenyls and
Terphenyls from Chalcones and Allylsulfones Terphenyls
from Chalcones and Allylsulfones under
under Phase Transfer Catalysis Conditions Phase Transfer Catalysis Conditions
Article
Domenico C. M. Albanese 1,*, Selene Brunialti 1 and Dario Destro 2 Domenico
C. M. Albanese 1, *, Selene Brunialti 1 and Dario Destro 2
1 Department of Chemistry, Università degli Studi di Milano, via Golgi 19, Milano 20133, Italy; 1
Department of Chemistry, Università degli Studi di Milano, via Golgi 19, Milano 20133, Italy;
[email protected] [email protected]
Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, 2
Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green,
Dublin 2, Ireland; [email protected] Dublin 2, Ireland; [email protected]
* Correspondence: [email protected]; Tel.: +39‐02‐5031‐4165 * Correspondence: [email protected]; Tel.: +39-02-5031-4165
Academic Editor: Keith Hohn Academic
Editor: Keith Hohn
Received: 15 July 2016; Accepted: 07 September 2016; Published: date Received: 15 July 2016; Accepted: 7 September 2016; Published: 13 September 2016
2
Abstract: Easily
Easily available
available chalcones
chalcones and
and allyl
allyl sulfones
sulfones along
along with
with cheap
cheap solid
solid NaOH
NaOH and
and Abstract:
polyethyleneglycol (PEG) 1000 have been used to directly generate the meta‐terphenyl or polyethyleneglycol (PEG) 1000 have been used to directly generate the meta-terphenyl or quaterphenyl
quaterphenyl motifs Transfer
under Phase Transfer Catalysis conditions.
solventless conditions. The new provides
approach motifs
under Phase
Catalysis
solventless
The new approach
provides an economic and environmentally friendly solution to removal of hazardous bases as well an economic and environmentally friendly solution to removal of hazardous bases as well as
as organic solvents. organic
solvents.
Keywords: terphenyls; quaterphenyls; Phase Transfer Catalysis; PEG; green chemistry; solventless Keywords:
terphenyls; quaterphenyls; Phase Transfer Catalysis; PEG; green chemistry; solventless
1.1. Introduction Introduction
The synthesis
synthesis of
of polysubstituted
polysubstituted aromatic
aromatic compounds
compounds relies
relies on
on various
various strategies
strategies involving
involving The
multistep approaches
approaches using organometallic species [1–5] or cycloadditions or under or multistep
using
organometallic
species
[1–5]
or cycloadditions
[6,7],[6,7], or under
acid oracid basic
basic reaction conditions [8]. reaction conditions [8].
The synthesis of terphenyls has recently aroused a great deal of interest since this skeleton has The
synthesis of terphenyls has recently aroused a great deal of interest since this skeleton
been found in many natural products, for example fungi, exhibiting diverse bioactivity [9]. Moreover, has been found in many natural products, for example fungi, exhibiting diverse bioactivity [9].
meta‐terphenyls have been have
used been
as ligands as intermediates for the synthesis of covalent Moreover,
meta-terphenyls
used as[10], ligands
[10], as intermediates
for the synthesis
of
0 ,50000 -sulfonyl-dinanostructures [11] and electron transporting material [12]. covalent
nanostructures
[11]as and
as electron
transporting
material
[12].For For example, example, 55′,5′′′′‐sulfonyl‐di‐
0 :30 ,100 ]-terphenyl (BTPS, [1,1′:3′,1′′]‐terphenyl Scheme 1),
1), bearing
bearing two
two meta-terphenyl
meta‐terphenyl subunits,
subunits, has
has been
been recently
recently [1,1
(BTPS, Scheme
prepared from bis(3,5‐dichlorophenyl)sulfone [13] by Suzuki‐Miyaura coupling in order to develop prepared
from bis(3,5-dichlorophenyl)sulfone [13] by Suzuki-Miyaura coupling in order to develop
new highly efficient organic light emitting diodes (OLED) [14]. new
highly efficient organic light emitting diodes (OLED) [14].
Cl
Cl
O
S
O
Cl
Ph
PhB(OH) 2
Cl
Pd 2(dba)3 /PCy 3
K3 PO 4
71%
Ph
O
S
O
BTPS
Ph
Ph
Scheme 1. Synthesis of 50 ,50000 -sulfonyl-di-[1,10 :30 ,100 ]-terphenyl (BTPS).
Scheme 1. Synthesis of meta‐terphenyl BTPS. BTPS, 5′,5′′′′‐sulfonyl‐di‐[1,1′:3′,1′′]‐terphenyl. Although several procedures allow the synthesis of the terphenyl skeleton, the development of Although
several procedures allow the synthesis of the terphenyl skeleton, the development of
alternative methods is still an issue since the regioselective construction of carbon–carbon bonds is a alternative methods is still an issue since the regioselective construction of carbon–carbon bonds is
agoal not always easy to be achieved. goal not always easy to be achieved.
A more practical approach to terphenyls has been realized by direct procedures capable of
generating
the central benzene ring with
available reagents.
Catalysts 2016, 6, 142; doi:10.3390/catal6090142
a single reaction involving easily www.mdpi.com/journal/catalysts Catalysts 2016, 6, 142; doi:10.3390/catal6090142
www.mdpi.com/journal/catalysts
Catalysts 2016, 6, 142 Catalysts 2016, 6, 142 2 of 9 2 of 9 Catalysts 2016, 6, 142
2 of 9
A more more practical practical approach approach to to terphenyls terphenyls has has been been realized realized by by direct direct procedures procedures capable capable of of A generating the central benzene ring with a single reaction involving easily available reagents. generating the central benzene ring with a single reaction involving easily available reagents. For example,
example, the
the Morita‐Baylis‐Hillman reaction of nitroalkenes nitroalkenes 1 alkylidene
and alkylidene alkylidene malono For
Morita-Baylis-Hillman
reaction
of nitroalkenes
1 and1 malonomalono nitriles
For example, the Morita‐Baylis‐Hillman reaction of and nitriles 2 gave good yields of the desired substituted terphenyls 3 under mild conditions (Scheme 2). 2nitriles 2 gave good yields of the desired substituted terphenyls 3 under mild conditions (Scheme 2). gave good yields of the desired substituted terphenyls 3 under mild conditions (Scheme 2). However,
However, this approach the for to the this
approach
suffers
from suffers the needfrom for additional
to preparesteps reactants
and the reactants formationand of toxic
However, this approach suffers from the need need steps
for additional additional steps to prepare prepare reactants and the formation of toxic HCN during annulation [15]. HCN
during annulation [15].
formation of toxic HCN during annulation [15]. Scheme
2. Morita-Baylis-Hillman route to meta-terphenyls.
Scheme 2. Morita‐Baylis‐Hillman route to meta‐terphenyls. Scheme 2. Morita‐Baylis‐Hillman route to meta‐terphenyls. On the other hand, a mixture of meta‐terphenyl 6a along with sulfonyl‐meta‐terphenyl 8a has On
the other hand, a mixture of meta-terphenyl 6a along with sulfonyl-meta-terphenyl 8a has been
On the other hand, a mixture of meta‐terphenyl 6a along with sulfonyl‐meta‐terphenyl 8a has been obtained by reacting allylsulfone 4a with chalcone 5a in the presence of excess of NaH in THF obtained
by reacting allylsulfone 4a with chalcone 5a in the presence of excess of NaH in THF at 50 ◦ C
been obtained by reacting allylsulfone 4a with chalcone 5a in the presence of excess of NaH in THF at 50 °C (Scheme 3) [16]. By the same approach, 1,2,4‐quaterphenyls 7a can also be obtained by using (Scheme
3) [16]. By the same approach, 1,2,4-quaterphenyls 7a can also be obtained by using an aryl
at 50 °C (Scheme 3) [16]. By the same approach, 1,2,4‐quaterphenyls 7a can also be obtained by using an aryl substituted allyl sulfone 4b [17]. substituted
allyl sulfone 4b [17].
an aryl substituted allyl sulfone 4b [17]. Scheme 3. Base promoted route to meta‐terphenyls. green benzenic rings are used to Scheme 3.
3. Base
Base promoted
promoted route
route to
to meta-terphenyls.
meta‐terphenyls. The The red and green benzenic
benzenic rings
rings are
are used
used to
to Scheme
The red red and and green
highlight the position of aryl groups of the starting chalcone in the produced meta‐terphenyl. highlight the position of aryl groups of the starting chalcone in the produced meta‐terphenyl. highlight
the position of aryl groups of the starting chalcone in the produced meta-terphenyl.
The aryl groups in the 1,3‐position of meta‐terphenyls 6 derive from the starting chalcones 5; The aryl
aryl groups in the 1,3‐position The
groups in the
1,3-position of meta‐terphenyls of meta-terphenyls 6 6 derive derive from from the the starting starting chalcones chalcones 5; 5;
therefore, a variety of substituted terphenyls can be prepared by using substituted chalcones, easily therefore, a variety of substituted terphenyls can be prepared by using substituted chalcones, easily therefore, a variety of substituted terphenyls can be prepared by using substituted chalcones,
accessed by Claisen‐Schmidt condensation of with aldehydes. Sulfones are accessed by the the condensation of methylketones methylketones with aldehydes. Sulfones are easily
accessed
byClaisen‐Schmidt the Claisen-Schmidt
condensation
of methylketones
with
aldehydes.
Sulfones
versatile intermediates intermediates used used in in many different many different applications [18–21]. Sulfones applications [18–21]. Sulfones 4a and 4c 4a and 4c have have been been versatile are versatile intermediates used in many different applications [18–21]. Sulfones 4a and 4c have been
prepared by alkylation of the proper sulfinic acid with allyl bromide or chloride under prepared by
by alkylation
alkylation proper sulfinic bromide or cinnamyl cinnamyl chloride prepared
ofof thethe proper
sulfinic
acidacid withwith allylallyl bromide
or cinnamyl
chloride
under under Phase
Phase Transfer Catalysis (PTC) conditions. Phase Transfer Catalysis (PTC) conditions. Transfer
Catalysis (PTC) conditions.
However, this approach requires the use of excess NaH (4 equiv) in order to deprotonate the However, this approach requires the use of excess NaH (4 equiv) in order to deprotonate the However,
this approach requires the use of excess NaH (4 equiv) in order to deprotonate the
allylsulfone, thus triggering the reaction cascade leading to terphenyls [16]. Moreover, the hydrogen allylsulfone, thus triggering the reaction cascade leading to terphenyls [16]. Moreover, the hydrogen allylsulfone, thus triggering the reaction cascade leading to terphenyls [16]. Moreover, the hydrogen
evolution and and the the need need to to remove remove THF THF before aqueous aqueous work‐up work‐up of of the the crude crude reaction reaction mixture mixture evolution evolution
and the
need to remove
THF beforebefore aqueous work-up
of the crude
reaction mixture
constitute
constitute additional additional drawbacks. drawbacks. Under Under such such reaction reaction conditions conditions huge huge amounts amounts of of sulfonyl‐meta‐
sulfonyl‐meta‐
constitute additional drawbacks. Under such reaction conditions huge amounts of sulfonyl-meta-terphenyls
terphenyls (30%–53% yield) are generated along with the desired products (40%–53% yield). terphenyls (30%–53% yield) are generated along with the desired products (40%–53% yield). (30%–53%
yield) are generated along with the desired products (40%–53% yield).
In order to develop a more practical approach and increase the selectivity, we planned to carry In order to develop a more practical approach and increase the selectivity, we planned to carry In
order to develop a more practical approach and increase the selectivity, we planned to carry
out this reaction under PTC conditions [22–27]. In fact, PTC represents a powerful tool to replace out this
this reaction
reaction under
under PTC conditions [22–27]. PTC represents
represents a powerful tool
tool to
to replace
replace out
PTC conditions
[22–27]. In fact, In fact, PTC
a powerful
hazardous and relatively expensive reactants such as NaH with cheap and practical bases such as hazardous and relatively expensive reactants such as NaH with cheap and practical bases such as hazardous and relatively expensive reactants such as NaH with cheap and practical bases such as
alkaline carbonates carbonates and and hydroxides hydroxides [28]. [28]. In In addition, addition, mild mild reaction reaction conditions, conditions, safety, safety, operational operational alkaline alkaline
carbonates and
hydroxides [28].
In addition, mild
reaction conditions,
safety, operational
simplicity, and high selectivity are widely accepted typical features of PTC processes that allow an simplicity, and high selectivity are widely accepted typical features of PTC processes that allow an simplicity,
and high selectivity are widely accepted typical features of PTC processes that allow an
easy scale‐up of reactions. easy scale‐up of reactions. easy
scale-up of reactions.
2. Results and Discussion 2. Results and Discussion 2.
Results and Discussion
Here we
we report
report that the synthesis of a variety variety of meta‐terphenyls meta‐terphenyls and quaterphenyls quaterphenyls can be be Here we report that synthesis a of and can Here
that
thethe synthesis
of aof variety
of meta-terphenyls
and quaterphenyls
can be carried
carried out in a chemoselective fashion by using NaOH as base under solid‐liquid (SL) PTC carried out in a chemoselective fashion by using NaOH base under (SL) PTC out
in a chemoselective
fashion by using
NaOH
as base
underas solid-liquid
(SL)solid‐liquid PTC conditions.
conditions. conditions. A preliminary set of reactions using allylsulfone 4a and chalcone 5a showed that solid NaOH
was capable to promote the reaction, whereas solid K2 CO3 or K3 PO4 were less effective. On the other
Catalysts 2016, 6, 142 3 of 9 Catalysts 2016, 6, 142
3 of 9
A preliminary set of reactions using allylsulfone 4a and chalcone 5a showed that solid NaOH was capable to promote the reaction, whereas solid K2CO3 or K3PO4 were less effective. On the other hand, 1,5‐diazabiciclo[5.4.0]undec‐5‐ene (1.5 hand, no no conversion conversion was was observed observed by by using using 1,5-diazabiciclo[5.4.0]undec-5-ene
(1.5 equiv) equiv) as as base base
under homogeneous conditions in THF as solvent. Although similar selectivity was observed by under homogeneous conditions in THF as solvent. Although similar selectivity was observed by using
using stoichiometric or NaOH,
excess NaOH, it was preferred to use excess NaOH since higher yields of stoichiometric
or excess
it was preferred
to use excess
NaOH
since
higher yields
of terphenyls
terphenyls could be obtained (Table 1, entries 1 and 2). could be obtained (Table 1, entries 1 and 2).
Table 1. Synthesis of meta‐terphenyls 6 under Phase Transfer Catalysis (PTC) conditions Table 1. Synthesis of meta-terphenyls 6 under Phase Transfer Catalysis (PTC) conditions aa. .
Entry
Entry 1 1
2
2 3
b
4
3 c
5
4 b 6
5 c 7
8
6 9
7 10
11
a
8 Catalyst
(equiv)
Chalcone
(%)
Catalyst (equiv) Chalcone Solvent
Solvent t (h)
t (h) 6 (%)
6 (%) 88 (%) NaOH (1)
TEBA (0.1)
5a
Toluene
13
23
NaOH (1) TEBA (0.1) 5a Toluene 3 3 13 23 NaOH (4)
TEBA (0.1)
5a
Toluene
3
20
28
NaOH (4) TEBA (0.1) NaOH (4)
TEBA
(0.1)
5a 5a CHToluene
3 3 1420 1728 3 CN
NaOH (4)
TEBA (0.1)
5a
CH3 CN
5
29
14 17 NaOH (4) TEBA (0.1) 5a CH3CN 3 3 NaOH (4)
TEBA (0.1)
5a
CH3 CN
3
38
36
NaOH (4) TEBA (0.1) CH3CN 1 3 NaOH (4)
TEBA
(0.1)
5a 5a DMSO
31 5 829 NaOH (4)
TEBA (0.1)
5b
DMSO
3
23
6
NaOH (4) TEBA (0.1) 5a CH3CN
3 38 36 NaOH (4)
TEBA (0.1)
5c
DMSO
3
39
2
NaOH (4) TEBA (0.1) DMSO 3 1 (C3 H7 )4 NOH 1M
(1)
5a 5a Toluene
3131 8 8 50% NaOH (4.1)
Bu4 N+ HSO4 − (0.1)
5a
Toluene
11
26
NaOH (4) TEBA (0.1) 5b DMSO 21 3 23 6 NaOH (4)
PEG 1000 (0.4)
5a
–
1
22
–
Base (equiv)
Base (equiv) NaOH (4) TEBA (0.1) 5c DMSO
3 39 2 5a Toluene
3 31 8 Reaction conditions: 4a (0.4 mmol), 5a (0.4 mmol), TEBA (0.04 mmol), 70 ◦ C; b 4a (0.8 mmol); c 5a (0.8 mmol).
9 (C3H7)4NOH 1M (1) +
−
4
4N HSO (0.1)in the 5a Toluene
21 base11 26 various
10 50% NaOH (4.1) Busignificantly
The reaction
did not proceed
presence
of 10% of
only, and
11 ammonium
NaOH (4) 5a – chloride
1 (TEBA),
22 – quaternary
salts suchPEG 1000 (0.4) as triethylbenzylammonium
Aliquat
and
a
b
tetrabutylammonium
hydrogensulfate (TBAHSO4 ) gave similar results both as
regards the yield
Reaction conditions: 4a (0.4 mmol), 5a (0.4 mmol), TEBA (0.04 mmol), 70 °C; 4a (0.8 mmol); c 5a (0.8 mmol). and chemoselectivity.
In toluene the main product was sulfonyl-meta-terphenyl 8a whereas nearly equimolar amounts
The reaction did not proceed significantly in the presence of 10% of base only, and various of meta-terphenyl 6a and 8a were obtained in CH3 CN (Table 1, entries 1–3).
quaternary ammonium salts such as triethylbenzylammonium chloride (TEBA), Aliquat and When the reaction has been carried out in the presence of a molar excess of allylsulfone 1a,
tetrabutylammonium hydrogensulfate (TBAHSO4) gave similar results both as regards the yield and the sulfonyl-meta-terphenyl 8a was isolated as the major compound (Table 1, entry 4). It was also
chemoselectivity. found that an excess of chalcone 5a provided higher yields of products 6a and 8a, although with the
In toluene the main product was sulfonyl‐meta‐terphenyl 8a whereas nearly equimolar amounts same selectivity (Table 1, entry 5). A good selectivity favoring the desired meta-terphenyl was obtained
of meta‐terphenyl 6a and 8a were obtained in CH3CN (Table 1, entries 1–3). in DMSO (Table 2, entry 6). Similar results have been obtained by using substituted chalcones 5b and
When the reaction has been carried out in the presence of a molar excess of allylsulfone 1a, the 5c (Table 1, entries 7 and 8).
sulfonyl‐meta‐terphenyl 8a was isolated as the major compound (Table 1, entry 4). It was also found Since the results suggested a possible positive influence of solvent polarity on the selectivity to 6a,
that an excess of chalcone 5a provided higher yields of products 6a and 8a, although with the same more practical alternatives to DMSO were sought.
selectivity (Table 1, entry 5). A good selectivity favoring the desired meta‐terphenyl was obtained in When a stoichiometric amount of (C3 H7 )4 NOH was used as base and catalyst in toluene, a good
DMSO (Table 2, entry 6). Similar results have been obtained by using substituted chalcones 5b and selectivity towards the desired meta-terphenyl was observed (Table 1, entry 9). On the other hand,
5c (Table 1, entries 7 and 8). a reversed selectivity was obtained by working under liquid-liquid PTC conditions using 50% aq.
Since the results suggested a possible positive influence of solvent polarity on the selectivity to NaOH/toluene biphasic system (Table 1, entry 10).
6a, more practical alternatives to DMSO were sought. The well-known metal cation coordination ability of polyethyleneglycols (PEG) [29], and the
When a stoichiometric amount of (C3H7)4NOH was used as base and catalyst in toluene, a good appropriate physical and solvent properties of low molecular weight liquid/low melting solid
selectivity towards the desired meta‐terphenyl was observed (Table 1, entry 9). On the other hand, a PEG, suggested us to use PEG 1000 as a Phase Transfer Catalyst. In fact, it is a low melting solid
reversed selectivity was obtained by working under liquid‐liquid PTC conditions using 50% aq. (mp 37–40 ◦ C) easier to manipulate than viscous PEG 400. We were indeed delighted to find that the
NaOH/toluene biphasic system (Table 1, entry 10). best result as regards to the selectivity was achieved when the reaction was carried out in the presence
The well‐known metal cation coordination ability of polyethyleneglycols (PEG) [29], and the of PEG 1000 as catalyst, without any other solvent (Table 1, entry 11). Indeed the desired terphenyl 6a
appropriate physical and solvent properties of low molecular weight liquid/low melting solid PEG, was isolated as a single compound, although in modest yield.
suggested us to use PEG 1000 as a Phase Transfer Catalyst. In fact, it is a low melting solid (mp 37–
Higher yields of the desired terphenyl 6a can be obtained by working under unselective conditions
40 °C) easier to manipulate than viscous PEG 400. We were indeed delighted to find that the best in CH3 CN as solvent (Table 1, entry 5) affording good yields of the combined terphenyls mixture
Catalysts 2016, 6, 142 4 of 9 result as regards to the selectivity was achieved when the reaction was carried out in the presence of PEG 1000 as catalyst, without any other solvent (Table 1, entry 11). Indeed the desired terphenyl 6a was isolated as a single compound, although in modest yield. Catalysts 2016, 6, 142
4 of 9
Higher yields of the desired terphenyl 6a can be obtained by working under unselective conditions in CH3CN as solvent (Table 1, entry 5) affording good yields of the combined terphenyls mixture + 8a), followed by desulfonylation in convert
order to 8a to the 6a. mixture
Thus, the (6a + 8a),(6a followed
by desulfonylation
in order to
8aconvert to the desired
6a.desired Thus, the
of
mixture of 6a and 8a was dissolved in THF, cooled to −80 °C, and dropwise added to a stirred THF 6a and 8a was dissolved in THF, cooled to −80 ◦ C, and dropwise added to a stirred THF solution of
solution of freshly sodium
prepared sodium naphthalenide solution −80 °C. The meta‐terphenyl 6a was freshly prepared
naphthalenide
solution at −80 ◦ C.at The
meta-terphenyl
6a was isolated
isolated in a 72% overall yield by quenching with water after 40 min, followed by usual work‐up and in a 72% overall yield by quenching with water after 40 min, followed by usual work-up and
chromatographic purification. chromatographic purification.
In determine the sulfone on the outcome
outcome of
of the
the reaction,
reaction, the In order order to to determine
the influence influence of of the the sulfone
on the
the
(cinnamylsulfonyl)benzene (4c) was reacted chalcone 5a under the previously optimized (cinnamylsulfonyl)benzene (4c)
was
reacted
withwith chalcone
5a under
the previously
optimized
reaction
reaction conditions (Table 2). conditions (Table 2).
Table 2. Synthesis of quaterphenyls 7 under PTC conditions Table 2. Synthesis of quaterphenyls 7 under PTC conditions aa. .
Entry
Entry Base (equiv)
Base (equiv) 1
1 2b
32 b 4
3 5
64 7
NaOH (4)
NaOH (4)
NaOH (4) NaOH
(1.1)
NaOH (4)
NaOH (1.1) NaOH (4)
NaOH (4) NaOH (4)
NaOH (4)
5 NaOH (4) NaOH (4) a
Catalyst
(equiv)
Chalcone
(h)
Catalyst (equiv)
Chalcone Solvent
Solvent t t (h)
Aliquat (0.1)
5a
DMSO
1
Aliquat (0.1) 5a DMSO
1 Aliquat (0.1)
5a
DMSO
1
Aliquat (0.1) DMSO
Aliquat
(0.1)
5a 5a DMSO
3 1 –
5a
DMSO
1
Aliquat (0.1) 5a DMSO
3 PEG 1000 (0.4)
5a
–
1
– (1.2)
DMSO
PEG 1000
5a 5a –
1 1 PEG 1000 (0.1)
5a
–
1
7a (%)
7a (%) 9a (%)
9a (%) 65
60
60 48
42
48 66
42 58
41
–
5
5 9
24
9 –
24 –
–
65 PEG 1000 (0.4) 5a – 1 66 Reaction conditions: 4c (0.4 mmol), 5 (0.4 mmol), 70 ◦ C; b at 100 ◦ C.
– – 6 NaOH (4) PEG 1000 (1.2) 5a – 1 58 – 7 NaOH (4) PEG 1000 (0.1) 5a – 1 41 – When the reaction was carried out in the presence of Aliquat as catalyst in DMSO, only the desired
a Reaction conditions: 4c (0.4 mmol), 5 (0.4 mmol), 70 °C; b at 100 °C. 1,2,4-triphenylbenzene
7a was recovered in 65% yield (Table 2, entry 1). When the temperature was
◦
increased
100reaction C a slight
of the
of presence 7a was observed
along
with thein formation
of 5%the of
When tothe was drop
carried out yield
in the of Aliquat as catalyst DMSO, only the
sulfonyl
derivative
9a
(Table
2,
entry
2).
Lower
yield
of
7a
was
obtained
by
using
1.1
equiv
of
desired 1,2,4‐triphenylbenzene 7a was recovered in 65% yield (Table 2, entry 1). When the NaOH, whereas a sharp decrease in selectivity was observed without Aliquat (Table 2, entries 3 and 4).
temperature was increased to 100 °C a slight drop of the yield of 7a was observed along with the A completely chemoselective reaction was obtained in the presence of PEG 1000 (0.4 equiv) without
formation of 5% of the sulfonyl derivative 9a (Table 2, entry 2). Lower yield of 7a was obtained by organic1.1 solvent
2, entry
5). Lower
yields
were obtained
when lower
or higher without amountsAliquat of PEG
using equiv (Table
of NaOH, whereas a sharp decrease in selectivity was observed were used (Table 2, entries 6 and 7).
(Table 2, entries 3 and 4). A completely chemoselective reaction was obtained in the presence of PEG Although the two chemoselective methods gave similar results (Table 2, entries 1 and 5) the
1000 (0.4 equiv) without organic solvent (Table 2, entry 5). Lower yields were obtained when lower reaction scope was investigated using the method employing PEG 1000 since it is more practical and
or higher amounts of PEG were used (Table 2, entries 6 and 7). economic.
In fact,
1000 is a cheap,methods easy to handle
solid that
successfully
Aliquat,
Although the PEG
two chemoselective gave similar results (Table 2, replace
entries both
1 and 5) the a
viscous
liquid,
and
DMSO,
a
dipolar
aprotic
solvent
that
is
difficult
to
remove
completely
from
the
reaction scope was investigated using the method employing PEG 1000 since it is more practical and reaction mixture. Moreover, 160 mg of PEG 1000 only are used to promote the reaction instead of
economic. In fact, PEG 1000 is a cheap, easy to handle solid that successfully replace both Aliquat, a 16 mg of Aliquat along with 1.1 g of DMSO.
viscous liquid, and DMSO, a dipolar aprotic solvent that is difficult to remove completely from the A variety of substituted chalcones 5b–h afforded the corresponding 1,2,4-triphenylbenzenes 7b–h
reaction mixture. Moreover, 160 mg of PEG 1000 only are used to promote the reaction instead of 16 in 51%–71% yield (Table 3).
mg of Aliquat along with 1.1 g of DMSO. A variety of substituted chalcones 5b–h afforded the corresponding 1,2,4‐triphenylbenzenes 7b–
h in 51%–71% yield (Table 3). Catalysts 2016, 6, 142
5 of 9
Catalysts 2016, 6, 142 Catalysts 2016, 6, 142 Catalysts 2016, 6, 142 Catalysts 2016, 6, 142 Catalysts 2016, 6, 142 5 of 9 5 of 9 5 of 9 5 of 9 5 of 9 Table 3. Synthesis of quaterphenyls under solventless PTC conditions a .
aaa. aaa
Table 3. Synthesis of quaterphenyls under solventless PTC conditions a. Table 3. Synthesis of quaterphenyls under solventless PTC conditions Table 3. Synthesis of quaterphenyls under solventless PTC conditions Table 3. Synthesis of quaterphenyls under solventless PTC conditions . . a. Table 3. Synthesis of quaterphenyls under solventless PTC conditions Entry
Calchone
5
Quaterphenyl
7
Yield (%)
Entry Calchone 5 Quaterphenyl 7
Yield (%) Entry Calchone 5 Quaterphenyl 7
Yield (%) Entry Calchone 5 Quaterphenyl 7
Yield (%) Entry Calchone 5 Quaterphenyl 7
Yield (%) Entry Calchone 5 Quaterphenyl 7
Yield (%) 71 71 71 71 71 71
1 111 11 2 2 2 2 2 2 69 69 69 69 69 69
3 3 3 3 3 3 3 70 70 70 70 70 70 70
b 4 b4 4 4 b b b 4 4 b b b b 19 19 19 19 19 19
c5 c c c 5 5 5 5 5 5 c c c c c 5e 5e
5e 5e 5e 5e 7e
7e
7e7e
7e
7e
15 15 15 15 15 15
63 63 63 63 63 63
6 6 6 6 6 6 51 51 51 51 51 51
7 7 7 7 7 7 63 63 63 63 63 63
8 8 8 8 8 8 bbb 4c (0.4 mmol), ◦ C;
bbbb 4c (0.4 mmol), Reaction conditions: 4c (0.4 mmol), 5 (0.4 mmol), PEG 1000 (0.16 mmol), 1 h, 70 °C; b 4c (0.4 mmol), b4c
Reaction conditions: 4c (0.4 mmol), 5 (0.4 mmol), PEG 1000 (0.16 mmol), 1 h, 70 °C; Reaction conditions: 4c (0.4 mmol), 5 (0.4 mmol), PEG 1000 (0.16 mmol), 1 h, 70 °C; Reaction conditions: 4c (0.4 mmol), 5 (0.4 mmol), PEG 1000 (0.16 mmol), 1 h, 70 °C; 4c (0.4 mmol), conditions:
4c
(0.4
mmol),
5
(0.4
mmol),
PEG
1000
(0.16
mmol),
1
h,
70
(0.4 mmol),
Reaction conditions: 4c (0.4 mmol), 5 (0.4 mmol), PEG 1000 (0.16 mmol), 1 h, 70 °C; 4c (0.4 mmol), c
c
ccc 4c (0.4 mmol), 5e (0.4 mmol). 5e
(0.2
mmol);
4c
(0.4
mmol),
5e
(0.4
mmol).
c
c
4c (0.4 mmol), 5e (0.4 mmol). 5e (0.2 mmol); c
c
5e (0.2 mmol); 4c (0.4 mmol), 5e (0.4 mmol). 5e (0.2 mmol); 4c (0.4 mmol), 5e (0.4 mmol). 5e (0.2 mmol); 4c (0.4 mmol), 5e (0.4 mmol). 5e (0.2 mmol); aaa a aaa
a
a
Reaction
Good yields were obtained with electronwithdrawing or electrondonating groups on the Good yields were obtained with electronwithdrawing or electrondonating groups on the Good yields were obtained with electronwithdrawing or electrondonating groups on the Good yields were obtained with electronwithdrawing or electrondonating groups on the Good yields were obtained with electronwithdrawing or electrondonating groups on the Good yields were obtained with electronwithdrawing or electrondonating groups on the benzene
benzene ring of chalcones 5b, 5c and 5h (Table 3, entries 1, 2 and 8). Heteroaromatic chalcones 5f and benzene ring of chalcones 5b, 5c and 5h (Table 3, entries 1, 2 and 8). Heteroaromatic chalcones 5f and benzene ring of chalcones 5b, 5c and 5h (Table 3, entries 1, 2 and 8). Heteroaromatic chalcones 5f and benzene ring of chalcones 5b, 5c and 5h (Table 3, entries 1, 2 and 8). Heteroaromatic chalcones 5f and benzene ring of chalcones 5b, 5c and 5h (Table 3, entries 1, 2 and 8). Heteroaromatic chalcones 5f and ring
of chalcones 5b, 5c and 5h (Table 3, entries 1, 2 and 8). Heteroaromatic chalcones 5f and
5g were also shown to be good substrates for the reaction (Table 3, entries 6 and 7), whereas (E)‐4‐
5g were also shown to be good substrates for the reaction (Table 3, entries 6 and 7), whereas (E)‐4‐
5g were also shown to be good substrates for the reaction (Table 3, entries 6 and 7), whereas (E)‐4‐
5g were also shown to be good substrates for the reaction (Table 3, entries 6 and 7), whereas (E)‐4‐
5g were also shown to be good substrates for the reaction (Table 3, entries 6 and 7), whereas (E)‐4‐
5g
were also shown to
bebearing good
substrates
for
the
reaction
3, ring entries
6provided and
7), whereas
phenylbut‐3‐en‐2‐one (5d), a group instead of a benzene also good phenylbut‐3‐en‐2‐one (5d), bearing a methyl group instead of a benzene ring also provided good phenylbut‐3‐en‐2‐one (5d), bearing a methyl group instead of a benzene ring also provided good phenylbut‐3‐en‐2‐one (5d), bearing a methyl methyl group instead of of a (Table
benzene ring also provided good phenylbut‐3‐en‐2‐one (5d), bearing a group instead a ring also provided good phenylbut‐3‐en‐2‐one (5d), bearing a methyl methyl group instead of a benzene benzene ring also provided good (E)-4-phenylbut-3-en-2-one
(5d),
bearing
a
methyl
group
instead
of
a
benzene
ring
also
provided
yield of the terphenyl 7d (Table 3, entry 3). yield of the terphenyl 7d (Table 3, entry 3). yield of the terphenyl 7d (Table 3, entry 3). yield of the terphenyl 7d (Table 3, entry 3). yield of the terphenyl 7d (Table 3, entry 3). good The yield
of
the terphenyl
7d hydrocarbon (Table
3, entry7e, 3).
polycyclic aromatic bearing seven benzenic rings could be isolated, The polycyclic aromatic hydrocarbon 7e, bearing seven benzenic rings could be isolated, The polycyclic aromatic hydrocarbon 7e, bearing seven benzenic rings could be isolated, The polycyclic aromatic hydrocarbon 7e, bearing seven benzenic rings could be isolated, The polycyclic aromatic hydrocarbon 7e, bearing seven benzenic rings could be isolated, The
polycyclic
aromatic
hydrocarbon
7e,
bearing
seven
benzenic
rings
could
be
isolated,
although
although in low yield, when the bifunctional enone 5e was used as starting material. Similar results although in low yield, when the bifunctional enone 5e was used as starting material. Similar results although in low yield, when the bifunctional enone 5e was used as starting material. Similar results although in low yield, when the bifunctional enone 5e was used as starting material. Similar results although in low yield, when the bifunctional enone 5e was used as starting material. Similar results in
low
yield, when the bifunctional enone 5e was used as starting material. Similar results have been
have been obtained by using a stoichiometric or 0.5 equiv of the sulfone 4c (Table 3, entries 4 and 5). have been obtained by using a stoichiometric or 0.5 equiv of the sulfone 4c (Table 3, entries 4 and 5). have been obtained by using a stoichiometric or 0.5 equiv of the sulfone 4c (Table 3, entries 4 and 5). have been obtained by using a stoichiometric or 0.5 equiv of the sulfone 4c (Table 3, entries 4 and 5). have been obtained by using a stoichiometric or 0.5 equiv of the sulfone 4c (Table 3, entries 4 and 5). In summary, in this paper have described a new, practical and chemoselective obtained
by
using a stoichiometric
orwe 0.5
equiv
of
the sulfone
4cnew, (Table
3, entries
4 and
5).
summary, this paper we have described practical and chemoselective In summary, in this paper we have described a new, practical and chemoselective In In summary, in in this paper we have described a a a new, practical and chemoselective In summary, in this paper we have described new, practical and chemoselective environmentally friendly method for the assembly of meta‐terphenyl and 1,2,4‐tetraphenyl skeleton environmentally friendly method for the assembly of meta‐terphenyl and 1,2,4‐tetraphenyl skeleton In
summary,
in
this
paper
we
have
described
a
new,
practical
and
chemoselective
environmentally
environmentally friendly method for the assembly of meta‐terphenyl and 1,2,4‐tetraphenyl skeleton environmentally friendly method for the assembly of meta‐terphenyl and 1,2,4‐tetraphenyl skeleton environmentally friendly method for the assembly of meta‐terphenyl and 1,2,4‐tetraphenyl skeleton under PTC conditions. The method uses allyl sulfones 4 and chalcones 5 as easily available starting under PTC conditions. The method uses allyl sulfones 4 and chalcones 5 as easily available starting friendly
method for the assembly of meta-terphenyl and 1,2,4-tetraphenyl skeleton under PTC
under PTC conditions. The method uses allyl sulfones 4 and chalcones 5 as easily available starting under PTC conditions. The method uses allyl sulfones 4 and chalcones 5 as easily available starting under PTC conditions. The method uses allyl sulfones 4 and chalcones 5 as easily available starting materials along with cheap, solid NaOH and PEG 1000. Moreover, no organometallic species or inert materials along with cheap, solid NaOH and PEG 1000. Moreover, no organometallic species or inert materials along with cheap, solid NaOH and PEG 1000. Moreover, no organometallic species or inert conditions.
The method uses allyl sulfones 4 and chalcones 5 as easily available starting materials
materials along with cheap, solid NaOH and PEG 1000. Moreover, no organometallic species or inert materials along with cheap, solid NaOH and PEG 1000. Moreover, no organometallic species or inert atmosphere are required. In particular, the use of PEG 1000 as a PTC catalyst enables to avoid the use atmosphere are required. In particular, the use of PEG 1000 as a PTC catalyst enables to avoid the use atmosphere are required. In particular, the use of PEG 1000 as a PTC catalyst enables to avoid the use atmosphere are required. In particular, the use of PEG 1000 as a PTC catalyst enables to avoid the use along
with cheap, solid NaOH and PEG 1000. Moreover, no organometallic species or inert atmosphere
atmosphere are required. In particular, the use of PEG 1000 as a PTC catalyst enables to avoid the use of any organic solvent thus adding value to the procedure. The choice of PEG 1000 was found to be of any organic solvent thus adding value to the procedure. The choice of PEG 1000 was found to be of any organic solvent thus adding value to the procedure. The choice of PEG 1000 was found to be of any organic solvent thus adding value to the procedure. The choice of PEG 1000 was found to be of any organic solvent thus adding value to the procedure. The choice of PEG 1000 was found to be Catalysts 2016, 6, 142
6 of 9
are required. In particular, the use of PEG 1000 as a PTC catalyst enables to avoid the use of any
organic solvent thus adding value to the procedure. The choice of PEG 1000 was found to be crucial
in order to develop a completely chemoselective method generating the desired compounds 6 and 7
without formation of the corresponding sulfonylated byproducts 8 and 9.
Further work is in progress in order to increase the yield of meta-terphenyls 6 involving the use of
allylsulfone 4a and ascertain the role of PTC in the chemoselective reaction.
3. Experimental Section
3.1. Materials and Methods
Reagents and solvents were purchased from commercial suppliers and used as received, without
further purification. Melting points were determined with a BÜCHI 535 melting point apparatus
(BÜCHI, Flawil, Switzerland) and are corrected. NMR spectra were recorded with a Bruker Fourier 300
spectrometer (Bruker Billerica, Massachusetts, MA, USA). Chemical shifts are reported by using CHCl3
as an external standard (δ = 7.24 ppm for 1 H NMR and 77.0 for 13 C NMR). APT experiments were
used in the assignment of carbon spectra. Mass spectra (electrospray ionization (ESI) and atmospheric
pressure chemical ionization (APCI)) were measured with a LCQ Advantage Thermo-Finnigan LLC
spectrometer (Thermo-Finnigan LLC San Jose, California, CA, USA). Column chromatography on
silica gel (230–400 mesh) was performed by the flash technique. Petroleum ether (PE) refers to the
fraction boiling in the range of 40–60 ◦ C.
3.2. Synthesis of Sulfones 4 and Chalcones 5
Allyl sulfones 4a and 4c were prepared by alkylation of the proper commercially available sodium
arylsulfinate under PTC conditions. The following detailed procedure for 4a is typical.
1-(Allylsulfonyl)-4-methylbenzene (4a): in a two-neck flask provided with a reflux condenser and
calcium chloride drying tube sodium 4-methylbenzenesulfinate (8.91 g, 50 mmol) and TEBA (1.14 g,
5 mmol) were dissolved in CH3 CN (50 mL). Allyl bromide (4.23 g, 35 mmol) was added and the
mixture was heated and magnetically stirred at 70 ◦ C for 21 h. Some solid material formed during
reaction was dissolved by adding H2 O (5 mL) and the reaction mixture was then extracted with AcOEt
(3 × 20 mL). The organic layer was dried (MgSO4 ) and evaporated at reduced pressure. The crude
product was purified through a small silica plug (AcOEt/PE = 1:1) to give 5.36 g of the title compound
(78% yield). The analytical data match those reported in the literature [30].
3-Benzenesulfonylpropenylbenzene (4c). The title compound was generated in a 75% yield (6.78 g,
white solid, mp 110.6–112.0 ◦ C) with the same protocol described above for 4a and using cinnamyl
chloride (4.08 g, 35 mmol) instead of allyl bromide. The analytical data of 4c are consistent with those
reported in the literature [31].
Chalcones 5a and 5c are commercially available. Other chalcones have been prepared by the
Claisen-Schmidt condensation of methylketones with aldehydes [32] and their spectroscopic and
physical properties matched those reported in literature:
(E)-3-(4-bromophenyl)-1-phenylprop-2-en-1-one (5b) [33], (E)-4-phenylbut-3-en-2-one (5d) [34],
(2E,20 E)-3,30 -(1,4-phenylene)bis(1-phenylprop-2-en-1-one) (5e) [35], (E)-3-(3-methylthio phen-2-yl)
-1-phenylprop-2-en-1-one (5f) [36], (E)-3-(5-methylfuran-2-yl)-1-phenylprop-2-en-1-one (5g) [37],
(E)-1-(4-Chlorophenyl)-3-phenylprop-2-en-1-one (5h) [38].
3.3. General Procedure for the Synthesis of meta-Terphenyls 6a–c under PTC Conditions
In a screw cap vial allylsulfone 4a (79 mg, 0.40 mmol) and chalcone 5 (0.40 mmol) were dissolved
in DMSO (1 mL). Solid NaOH (1.6 mmol, 64 mg) and TEBA (0.04 mmol, 9 mg) were added and
the resulting mixture was stirred at 70 ◦ C until completion. The reaction mixture was quenched
with sat NH4 Cl solution and extracted with AcOEt (3 × 5 mL). The combined organic solution was
dried and evaporated to dryness. The pure compounds were obtained by column chromatography
(AcOEt/hexane from 1:20 to 1:3).
Catalysts 2016, 6, 142
7 of 9
1,10 :30 ,100 -terphenyl (6a): yield 22%; mp 86.5–87 ◦ C, lit. [16] mp 86–88 ◦ C. 1 H NMR (300 MHz,
CDCl3 ): δ 7.82 (m, 1H), 7.67–7.26 (m, 13 H). 13 C NMR (300 MHz, CDCl3 ): δ 141.7 (C), 141.1 (C), 129.0
(CH), 128.6 (CH), 127.2 (CH), 127.1 (CH), 126.0 (CH).
40 -sulfonyl-1,10 :20 ,100 -terphenyl (8a): 1 H NMR (300 MHz, CDCl3 ): δ 8.46 (m, 1H), 7.78–6.99
(m, 16H), 2.34 (s, 3H).
4-bromo-1,10 :30 ,100 -terphenyl (6b): yield 23%; mp 91–92 ◦ C, lit. [39] mp 91.5–92 ◦ C. 1 H NMR
(300 MHz, CDCl3 ): δ 7.78 (s, 1H), 7.61 (m,5H), 7.51 (m, 6H), 7.39(m, 1H). 13 C NMR (300 MHz, CDCl3 ):
δ 142.0 (C), 141.0 (C), 140.6 (C), 140.1 (C), 131.9 (CH), 129.3 (CH), 128.8 (CH), 127.5 (CH), 127.2 (CH),
126.5 (CH), 125.9 (CH), 125.9 (CH), 121.7 (C). 4-methoxy-1,10 :30 ,100 -terphenyl (6c): yield 39%, mp
122–123 ◦ C, lit. [40] mp 123–124 ◦ C. 1 H NMR (300 MHz, CDCl3 ): δ 7.76 (m, 1H), 7.66–7.374 (m, 10H),
7.00 (d, 2H, J = 9 Hz), 3.86(s, 3H). 13 C NMR (300 MHz, CDCl3 ): δ 159.2 (C), 141.6 (C), 141.3 (C), 141.2
(C), 133.6 (C), 129.0 (CH), 128.6 (CH), 18.1 (CH), 127.2 (CH), 127.1 (CH), 125.6 (CH), 125.4 (CH), 114.2
(CH), 55.2 (CH3 ).
3.4. General Procedure for the Solventless Synthesis of Quaterphenyls 8 under PTC Conditions
A screw cap vial was charged with allylsulfone 4c (0.40 mmol, 103 mg), chalcone 5 (0.40 mmol),
solid NaOH (1.6 mmol, 64 mg) and PEG 1000 (0.16 mmol, 162 mg). After stirring at 70 ◦ C until
completion, the reaction mixture was quenched with sat NH4 Cl solution and extracted with AcOEt
(3 × 5 mL). The combined organic solution was dried and evaporated to dryness. The pure compounds
were obtained by column chromatography (AcOEt/hexane from 1:20 to 1:3).
40 -phenyl-1,10 :20 ,100 -terphenyl (7a): yield 66%, mp 120.5–121 ◦ C, lit. [41] mp 121–122 ◦ C. 1 H NMR
(300 MHz, CDCl3 ): δ 7.75–7.69 (m, 4H), 7.59–7.48 (m, 3H), 7.44–7.40 (m, 1H), 7.28–7.24 (m, 10H).
4-bromo-50 -phenyl-1,10 :20 ,100 -terphenyl (7b): yield 71%, mp 210.5–211.2 ◦ C. 1 H NMR (300 MHz,
CDCl3 ): δ 7.63–7.50 (m, 7H), 7.26–7.16 (m, 10H). 13 C NMR (300 MHz, CDCl3 ): δ 141.3 (C), 141.2 (C),
141.0 (C), 140.0 (C), 139.5 (C), 139.1 (C), 131.9 (CH), 131.2 (CH), 129.8 (CH), 129.2 (CH), 128.7 (CH),
127.9 (CH), 126.7 (CH), 126.6 (CH), 125.9 (CH), 121.7 (C).
4-methoxy-50 -phenyl-1,10 :20 ,100 -terphenyl (7c): yield 69%, mp 165.4–166.0 ◦ C. 1 H NMR (300 MHz,
CDCl3 ): δ 7.66 (m, 4H), 7.53 (m, 1H), 7.25 (m, 10H), 7.04 (m, 2H), 3.90 (s, 3H). 13 C NMR (300 MHz,
CDCl3 ): δ 159.4 (C), 141.6 (C), 141.2 (C), 141.0 (C), 140.0 (C), 139.0 (C), 133.1 (C), 131.1 (CH), 129.9 (CH),
129.9 (CH), 129.0 (CH), 128.2 (CH), 127.9 (CH), 127.9 (CH), 126.6 (CH), 126.5 (CH), 125.7 (CH), 114.3
(CH), 55.4 (CH3 ).
20 -methyl-1,10 :40 ,100 -terphenyl (7d): yield 70%, mp 84.5–86.8 ◦ C. 1 H NMR (300 MHz, CDCl3 ):
δ 7.64 (m, 2H), 7.51–7.26 (m, 11H), 2.36 (s, 3H). 13 C NMR (300 MHz, CDCl3 ): δ 141.6 (C), 141.0 (2C),
140.2 (C), 135.8 (C), 130.3 (CH), 129.2 (CH), 129.1 (CH), 128.8 (C), 128.1 (CH), 127.2 (CH), 127.1 (CH),
126.9 (CH), 124.6 (CH), 20.7 (CH3 ).
40 ,5000 -diphenyl-1,10 :20 ,100 :400 ,1000 :2000 ,10000 -quinquephenyl (7e): yield 15%, mp 255.6–258.1 ◦ C.
1 H NMR (300 MHz, CDCl ): δ 7.79–7.06 (m, 30H). 13 C NMR (300 MHz, CDCl ): δ 141.5, 141.1,
3
3
139.7, 131.2, 131.1, 130.4, 129.9, 129.3, 128.8, 127.9, 127.5, 127.2, 126.6, 126.2, 126.0, 125.9. APCI–MS:
m/z = 535.3 [M + H]+ .
2-(20 -1,10 :40 ,100 -terphenyl)-3-methyl-thiophene (7f): yield 63%, mp 111.8–114.3 ◦ C. 1 H NMR
(300 MHz, CDCl3 ): δ 7.46–7.37 (m, 4H), 7.17–7.07 (m, 10H), 6.64 (d, 1H), 2.33 (s, 3H). 13 C NMR
(300 MHz, CDCl3 ): δ 141.2 (C), 141.1 (C), 140.7 (C), 139.4 (C), 137.3 (C), 134.0 (C), 133.4 (C), 131.1 (CH),
130.8 (CH), 129.90 (CH), 129.8 (CH), 127.9 (CH), 126.6 (CH), 126.6 (CH), 123.6 (CH), 15.1 (CH3 ).
2-(20 -1,10 :40 ,100 -terphenyl)-3-methyl-furan (7g): yield 51%, oil. 1 H NMR (300 MHz, CDCl3 ):
δ 7.7–7.2 (m, 13H), 6.61 (d, 1H, J = 3.2), 6.08 (d, 1H, J = 3.2), 2.39 (s, 3H). 13 C NMR (300 MHz,
CDCl3 ): δ 152.2 (C), 151.9 (C), 141.5 (C), 141.2 (C), 140.9 (C), 138.9 (C), 137.9 (C), 131–125 (13CH), 107.8
(CH2 ), 106.2 (CH2 ), 13.7 (CH3 ).
4-chloro-30 -phenyl-1,10 :40 ,100 -terphenyl (7h): yield 63%, mp 206.4–208.6 ◦ C. 1 H NMR (300 MHz,
CDCl3 ): δ 7.60–7.63 (m, 4H), 7.50–7.53 (m, 1H), 7.42–7.45 (m, 2H), 7.15–7.26 (m, 10H). 13 C NMR (300 MHz,
Catalysts 2016, 6, 142
8 of 9
CDCl3 ): δ 141.3 (C), 141.2 (C), 140.9 (C), 139.9 (C), 139.1 (C), 139.0 (C), 133.6 (C), 131.2 (CH), 129.8 (CH),
129.2 (CH), 129.0 (CH), 128.4 (CH), 128.0 (CH), 128.0 (CH), 126.7 (CH), 126.6 (CH), 125.9 (CH).
3.5. Desulfonation of the meta-Terphenyl (6a) and Sulphonyl-meta-terphenyl (8a) Mixture
The mixture of compounds 6a (0.152 mmol, 35 mg) and 8a (0.144 mmol, 55.4 mg), as recovered
after usual work-up of reaction carried out under condition reported in Table 1 (entry 5), was dissolved
in anhydrous THF (1 mL), cooled to −80 ◦ C and subsequently added to a stirred THF solution of
freshly prepared sodium naphthalenide (0.86 mmol) at −80 ◦ C. After 40 min at the same temperature
the reaction was quenched by water addition. The reaction mixture was allowed to come to room
temperature and was extracted with CH2 Cl2 (3 × 5 mL). The organic phase was dried over Na2 SO4 ,
evaporated under reduced pressure and purified by column chromatography (AcOEt/PE) to give
66 mg of meta-terphenyl (3a), overall yield 72%.
Author Contributions: Domenico C. M. Albanese conceived and designed the experiments; Selene Brunialti and
Dario Destro performed the experiments; Domenico C. M. Albanese analyzed the data; Domenico C. M. Albanese
and Selene Brunialti wrote the paper.
Conflicts of Interest: The authors declare no conflict of interest.
References and Note
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Cho, C.H.; Kim, I.S.; Park, K. Preparation of unsymmetrical terphenyls via the nickel-catalyzed cross-coupling
of alkyl biphenylsulfonates with aryl Grignard reagents. Tetrahedron 2004, 60, 4589–4599. [CrossRef]
Miguez, J.M.A.; Adrio, L.A.; Sousa-Pedrares, A.; Vila, J.M.; Hii, K.K. A practical and general synthesis of
unsymmetrical terphenyls. J. Org. Chem. 2007, 72, 7771–7774. [CrossRef] [PubMed]
Todd, M.H.; Balasubramanian, S.; Abell, C. Studies on the synthesis, characterisation and reactivity of
aromatic diboronic acids. Tetrahedron Lett. 1997, 38, 6781–6784. [CrossRef]
Shimizu, H.; Manabe, K. Negishi coupling strategy of a repetitive two-step method for oligoarene synthesis.
Tetrahedron Lett. 2006, 47, 5927–5931. [CrossRef]
Taylor, R.H.; Felpin, F.X. Suzuki–Miyaura reactions of arenediazonium salts catalyzed by Pd(0)/C. One-pot
chemoselective double cross-coupling reactions. Org. Lett. 2007, 9, 2911–2914. [CrossRef] [PubMed]
Saito, S.; Yamamoto, Y. Recent advances in the transition-metal-catalyzed regioselective approaches to
polysubstituted benzene derivatives. Chem. Rev. 2000, 100, 2901–2916. [CrossRef] [PubMed]
Zhang, L.; Liang, F.; Cheng, X.; Liu, Q. A new route to multifunctionalized p-terphenyls and heteroaryl
analogues via [5C + 1C(N)] annulation strategy. J. Org. Chem. 2009, 74, 899–902. [CrossRef] [PubMed]
Ballini, R.; Palmieri, A.; Bartoni, L. Nitroalkanes as new, ideal precursors for the synthesis of benzene
derivatives. Chem. Commun. 2008. [CrossRef] [PubMed]
Liu, J.K. Natural terphenyls: Developments since 1877. Chem. Rev. 2006, 106, 2209–2223. [CrossRef] [PubMed]
Kays, D.L. Recent developments in transition metal diaryl chemistry. Dalton Trans. 2011, 40, 769–778.
[CrossRef] [PubMed]
Fan, Q.; Wang, C.; Han, Y.; Zhu, J.; Kuttner, J.; Hilt, G.; Gottfried, J.M. Surface-assisted formation, assembly,
and dynamics of planar organometallic macrocycles and zigzag shaped polymer chains with C–Cu–C bonds.
ACS Nano 2014, 8, 709–718. [CrossRef] [PubMed]
Wu, C.A.; Chou, H.H.; Shih, C.H.; Wu, F.I.; Cheng, C.H.; Huang, H.L.; Chao, T.C.; Tseng, M.R. Synthesis and
physical properties of meta-terphenyloxadiazole derivatives and their application as electron transporting
materials for blue phosphorescent and fluorescent devices. J. Mater. Chem. 2012, 22, 17792–17799. [CrossRef]
Taylor, P.C.; Wall, M.D.; Woodward, P.R. Synthesis of dendritic oligo(aryl sulfone)s as supports for synthesis.
Tetrahedron 2005, 61, 12314–12322. [CrossRef]
Sasabe, H.; Seino, Y.; Kimura, M.; Kido, J. A m-terphenyl-modifed sulfone derivative as a host material for
high-efficiency blue and green phosphorescent OLEDs. Chem. Mater. 2012, 24, 1404–1406. [CrossRef]
Gopi, E.; Namboothiri, I.N. One-pot regioselective synthesis of meta-terphenyls via [3 + 3] annulation of
nitroallylic acetates with alkylidenemalononitriles. J. Org. Chem. 2014, 79, 7468–7476. [CrossRef] [PubMed]
Chang, M.Y.; Chan, C.K.; Lin, S.Y.; Wu, M.H. One-pot synthesis of multifunctionalized m-terphenyls.
Tetrahedron 2013, 69, 9616–9624. [CrossRef]
Catalysts 2016, 6, 142
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
9 of 9
Chang, M.Y.; Chan, C.K.; Lin, S.Y.; Wu, M.H. One-pot synthesis of multisubstituted quaterphenyls and
cyclopropanes. Tetrahedron 2013, 69, 10036–10044. [CrossRef]
El-Awa, A.; Noshi, M.N.; Mollat du Jourdin, X.; Fuchs, P.L. Evolving organic synthesis fostered by the
pluripotent phenylsulfone moiety. Chem. Rev. 2009, 109, 2315–2349. [CrossRef] [PubMed]
Trost, B.M. Chemical chameleons. organosulfones as synthetic building blocks. Bull. Chem. Soc. Jpn. 1988, 61,
107–124. [CrossRef]
Simpkins, N.S. Sulphones in Organic Synthesis; Pergamon: Oxford, UK, 1993.
Sulphones and Sulphoxides; Patai, S.; Rappoport, Z.Z.; Stirling, C. (Eds.) Wiley: Chichester, UK, 1988.
Dehmlow, E.V.; Dehmlow, S.S. Phase Transfer Catalysis, 3rd ed.; Wiley-VCH: Weinheim, Germany, 1993.
Starks, C.M.; Liotta, C.L.; Halpern, M. Phase-Transfer Catalysis; Chapman & Hall: New York, NY, USA, 1994.
Handbook of Phase-Transfer Catalysis; Sasson, Y.; Neumann, R. (Eds.) Blackie Academic & Professional: London,
UK, 1997.
Phase-Transfer Catalysis; Halpern, M.E. (Ed.) ACS Symposium Series 659; American Chemical Society:
Washington, DC, USA, 1997.
Albanese, D. Phase-Transfer Catalysis. In Kirk-Othmer Encyclopedia of Chemical Technology; John Wiley & Sons:
New York, NY, USA, 2008; pp. 1–22. [CrossRef]
Albanese, D.; Foschi, F.; Penso, M. Sustainable oxidations under phase-transfer catalysis conditions. Org. Proc.
Res. Dev. 2016, 20, 129–139. [CrossRef]
Albanese, D.; Landini, D.; Penso, M. Synthesis of 2-amino acids via selective mono-N-alkylation of
trichloroacetamide by 2-bromo carboxylic esters under solid-liquid phase-transfer catalysis conditions.
J. Org. Chem. 1992, 57, 1603–1605. [CrossRef]
Dramatically reduced cost of PEG related to crown ether discouraged us to test crown ethers as alternative
phase transfer catalysts.
Fukuda, N.; Ikemoto, T. Imide-catalyzed oxidation system: Sulfides to sulfoxides and sulfones. J. Org. Chem.
2010, 75, 4629–4631. [CrossRef] [PubMed]
Caldwell, J.J.; Craig, D.; East, S.P. Application of 5-endo-trig cyclisation in the total synthesis of (+)-preussin.
Arkivoc 2007, xii, 67–90.
Kohler, E.P.; Chadwell, H.M. Benzalacetophenone. Org. Synth. 1922, 2, 1.
Stroba, A.; Schaeffer, F.; Hindie, V.; Lopez-Garcia, L.; Adrian, I.; Fröhner, W.; Hartmann, R.W.; Biondi, R.M.;
Engel, M. 3,5-Diphenylpent-2-enoic acids as allosteric activators of the protein kinase PDK1: structure-activity
relationship and thermodynamic characterization of binding as paradigms for PIF-binding pocket-targeting
compounds PDB code of 2Z with PDK1:3HRF. J. Med. Chem. 2009, 52, 4683–4693. [CrossRef] [PubMed]
Gottumukkala, A.L.; Teichert, J.F.; Heijnen, D.; Eisink, N.; van Dijk, S.; Ferrer, C.; van den Hoogenband, A.;
Minnaard, A.J. Pd-Diimine: A highly selective catalyst system for the base-free oxidative Heck reaction.
J. Org. Chem. 2011, 76, 3498–3501. [CrossRef] [PubMed]
Bhat, A.R.; Athar, F.; Azam, A. Bis-pyrazolines: Synthesis, characterization and antiamoebic activity as
inhibitors of growth of Entamoeba hystolytica. Eur. J. Med. Chem. 2009, 44, 426–431. [CrossRef] [PubMed]
Li, W.; Wu, X.F. Ruthenium-catalyzed conjugate hydrogenation of α,β-enones by in situ generated
dihydrogen from paraformaldehyde and water. Eur. J. Org. Chem. 2015, 331–335. [CrossRef]
Jin, H.; Geng, Y.; Yu, Z.; Tao, K.; Hou, T. Lead optimization and anti-plant pathogenic fungi activities of
daphneolone analogues from Stellera chamaejasme L. Pestic. Biochem. Physiol. 2009, 93, 133–137. [CrossRef]
Schmink, J.R.; Holcomb, J.L.; Leadbeater, N.E. Testing the validity of microwave-interfaced, in situ Raman
spectroscopy as a tool for kinetic studies. Org. Lett. 2009, 11, 365–368. [CrossRef] [PubMed]
Bradsher, C.K.; Swerlick, I. Reactions in the m-terphenyl series. J. Am. Chem. Soc. 1950, 72, 4189–4192.
[CrossRef]
Beaumard, F.; Dauban, P.; Dodd, R.H. One-pot double Suzuki–Miyaura couplings: Rapid access to
nonsymmetrical tri(hetero)aryl derivatives. Org. Lett. 2009, 11, 1801–1804. [CrossRef] [PubMed]
Yoshida, K.; Morimoto, I.; Mitsudo, K.; Tanaka, H. RhCl3 /amine-catalyzed [2 + 2 + 2] cyclization of alkynes.
Tetrahedron 2008, 64, 5800–5807. [CrossRef]
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