GC/MSn analysis of the crude reaction mixtures from Friedel–Crafts acylation: Unambiguous identification and differentiation of 3-aroylbenzofurans from their 4- and 6-regioisomers

Article abstract of DOI:10.1002/rcm.9082

Rationale: 3-Aroylbenzofurans and their 2-nitrophenyl derivatives constitute fundamental intermediates for the synthesis of target compounds with pharmaceutical properties. However, their preparation via the Friedel–Crafts acylation of 2-phenylbenzofurans

Full text of DOI:10.1002/rcm.9082

Received: 12 January 2021
DOI: 10.1002/rcm.9082
Revised: 12 March 2021
Accepted: 13 March 2021
R E S E A R C H A R T I C L E
n
GC/MS analysis of the crude reaction mixtures from
Friedel–Crafts acylation: Unambiguous identification and
differentiation of 3-aroylbenzofurans from their 4- and
6
-regioisomers
1
2
3
Michela Begala
| Michele Mancinelli
| Elias Quezada
|
1
Giovanna Lucia Delogu
1
Department of Life and Environmental
Sciences, University of Cagliari, Cittadella
Universitaria, s.p.8, 09042 Monserrato,
Cagliari, Italy
Rationale: 3-Aroylbenzofurans and their 2-nitrophenyl derivatives constitute
fundamental intermediates for the synthesis of target compounds with
pharmaceutical properties. However, their preparation via the Friedel–Crafts
acylation of 2-phenylbenzofurans, using Lewis acid as catalyst, often leads to
mixtures of regioisomeric aroylbenzofurans that can be challenging to distinguish,
thus preventing the reaction characterization.
2
Department of Industrial Chemistry “Toso
Montanari”, University of Bologna, Viale del
Risorgimento 4, Bologna, 40136, Italy
3
Department of Organic Chemistry, University
of Santiago de Compostela, Santiago de
Compostela, 15782, Spain
Method: We report a method for the unambiguous identification and differentiation
of the desired 3-benzoyl isomers from their 4- and 6-regioisomers in a crude reaction
mixture using gas chromatography coupled to multiple-stage mass spectrometric
Correspondence
M. Begala, Department of Life and
Environmental Sciences, University of Cagliari,
Cittadella Universitaria, s.p.8, 09042
Monserrato, Cagliari, Italy.
n
(GC/MS ) analysis performed in collision-induced dissociation (CID) mode.
Results: Upon electron ionization, each set of isomers displayed nearly identical mass
Email: michelabegala@unica.it
n
spectra. MS revealed fragmentation patterns that varied in the location of
Funding information
the benzoyl group on the benzofuran scaffold: CID experiments performed on the
Fondo Integrativo per la Ricerca, Università di
Cagliari
molecular ion allowed the distinction of the 3-acyl isomers from the 4- and
+
6
-regioisomers; CID experiments on the [M − Ar] ion allowed the distinction of
the 4-benzoyl from the 6-benzoyl regioisomer, when the nitro group is located on
•
the 2-phenyl ring. Moreover, the unusual loss of OH radical allowed ascertaining the
position of the nitro group in 3-acyl regioisomers bearing the NO
2
group. The origin
18
•
n
of the diagnostic OH loss was investigated through MS experiments using O-
labelled 3-benzoyl derivatives.
Conclusions: The method allows the rapid characterization of crude reaction
n
mixtures of benzoylbenzofurans using solely GC/MS analysis, simplifying the
workflow of extensive isolation and purification for structure elucidation.
Michela Begala, supervisor and principal investigator.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
©
2021 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.
Rapid Commun Mass Spectrom. 2021;35:e9082.
wileyonlinelibrary.com/journal/rcm
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https://doi.org/10.1002/rcm.9082

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BEGALA ET AL.
1
|
INTRODUCTION
electron-withdrawing groups attenuate the reactivity and influence
8
position selectivity.
3
-Aroylbenzofurans represent an important class of heterocyclic
Monitoring the reaction progress is of great interest in modern
organic synthesis and drug research. However, thin-layer
chromatography is often ineffective for the analysis of complex
reaction mixture, such as that of various benzoylbenzofuran
regioisomers. Moreover, the purification and isolation of each benzoyl
isomer from their mixtures is often a very laborious process that
requires many manual steps to generate sufficiently pure compounds
for identification and reaction characterization. In a worst case, the
1–4
compounds in current pharmaceuticals use or development.
As a
result, various methods for the synthesis of 3-aroylbenzofurans have
been reported in the literature. The Friedel–Crafts acylation of
aromatic compounds is one of the most widely used chemical
reactions for the preparation of aromatic ketones at both academic
5
and industrial levels. However, during the Friedel–Crafts aroylation
of 2-substituted benzofurans, various positions of the benzofuran ring
6
9
are also acylated. More specifically, although aroylation occurs
minor component cannot be separated. Hence, the need for
predominantly at the 3-position, for most aroyl chlorides aroylation
sensitive methods that can rapidly identify benzoylbenzofuran
regioisomers becomes crucial from this standpoint, especially for
3-benzoyl-2-phenylbenzofurans containing nitro groups, as they could
provide convenient intermediates in the preparation of more
also occurs at the 6-position and to a lesser extent at the 4-position
7
(
Scheme 1; Figures 1A and 1B). A different regioisomer distribution
is observed in the acylation of benzofurans deactivated by a nitro
group on the 2-phenyl ring (Figure 1C). In this case, Friedel–Crafts
acylation leads to a mixture of regioisomers where the expected
10–12
complicated compounds.
In this paper, we report the gas chromatography coupled to
n
3
-acyl isomer is formed as a minor product, reasonably because
multiple-stage mass spectrometric (GC/MS ) analyses of three
SCHEME 1 Mixtures of regioisomers obtained by Friedel–Crafts acylation of 2-phenylbenzofurans
FIGURE 1 GC separation of the 3-benzoylbenzofurans 1a–c from their 4- and 6-benzoyl regioisomers 2a–c and 3a–c

BEGALA ET AL.
3 of 8
ꢀ ꢀ ꢀ
programmed from 80 C (held for 5 min) to 280 C at 20 C/min
series of isomeric mixtures of benzoylbenzofurans obtained via
Friedel–Crafts acylation of 2-phenylbenzofurans with benzoyl
chlorides (Figure 1 and Scheme 1), aiming to distinguish and to
identify, in the crude reaction mixtures, the 3-benzoyl isomers
ꢀ
ꢀ
(held for 5 min); this was increased to 300 C at 20 C/min (held
ꢀ
ꢀ
for 5 min). The temperature was then ramped to 350 C at 20 C/
ꢀ
min. The transfer line was maintained at 180 C and the injector
ꢀ
n
1
a–c from their 4- and 6-regioisomers 2a–c and 3a–c, respectively.
port (30:1 split) at 290 C. MS analyses were replicated five times.
The relative standard deviations of the relative peak intensities
were below 15% (Tables S1–S18); in the measurements, very
small peak are usually excluded and we used an intensity cutoff
of 2%.
n
For this aim, MS experiments, performed in collision-induced
dissociation (CID) mode, were carried out using a quadrupole ion
13
trap analyzer.
2
2
|
EXPERIMENTAL
| MS analysis
2
.2
|
Materials and reagents
.1
All reagents and solvents were purchased from Sigma-Aldrich
S.r.l. (Milan, Italy) and Carlo Erba Reagents S.r.l. (Milan, Italy) and used
without further purification.
All experiments were performed with a Varian Saturn 2000 ion trap
mass spectrometer, operating under electron ionization (EI) conditions
(
electron energy, 70 eV; emission current, 20 mA; ion trap
The crude reaction mixtures of regioisomers 1a–3a, 1b–3b and
1c–3c were prepared via direct Friedel–Crafts acylation of the
ꢀ
ꢀ
temperature, 220 C; manifold temperature, 80 C; automatic gain
control target, 21 000) with the ion trap operating in scan mode (scan
range m/z 40–500 at a scan rate of 1 scan/s), coupled with a Varian
3
respective 2-phenylbenzofuran with benzoyl chloride using AlCl as
8
Lewis acid in anhydrous dichloromethane (Scheme 1).
3
800 gas chromatograph (Varian, Walnut Creek, CA).
5 5 5
3-Benzoyl-2-phenyl-d -benzofurans 1ad –3ad were synthesized
CID experiments were carried out using helium as the collision
5
in the same way starting from 2-phenylbenzofuran-d and benzoyl
n
gas (gas purity was 99.9999%). For MS experiments the
supplementary rf voltage (45–55 V) was varied in such a way that the
relative abundance of the surviving precursor ions was 5%–15%. An
isolation time of 10 ms, an excitation time of 40 ms and an isolation
width of 1 m/z for the precursor ion were used. Each MS/MS
chloride.
Reference compounds 1a, 1b and 1c were prepared as reported
14,15
in our previous works.
2-Phenylbenzofuran,
2-phenylbenzofuran-d
5
and
from
2-(4-nitrophenyl)benzofuran
were
prepared
bromide
starting
and
spectrum was an average of five scans.
2-hydroxybenzyltriphenylphosphomium
5
chloride, benzoyl chloride-d or 4-nitrobenzoyl chloride, respectively,
benzoyl
Compounds under investigation (1 μL aliquots of 1.0 × 10−
5
M
solutions in dichloromethane) were introduced into the GC inlet.
To perform the GC separation, an Agilent J&W VF-5ms low-bleed/
MS GC capillary column (30 m, 0.25 mm i.d., 0.25 μm film
thickness; Agilent Technologies Inc., Wilmington, DE, USA) was
used with a flow of 1.0 mL/min. The oven temperature was
in toluene and Et
3
N using the procedure described in previous
14,16,17
works.
18
18
3-[ O]-Benzoyl-2-(4-nitrophenyl)benzofuran
(1c[ O])
was
prepared analogously to 1c starting from 2-(4-nitrophenyl)benzofuran
18
and [ O]-benzoyl chloride.
2
3
2
FIGURE 2 EI mass spectrum (A), MS of m/z 298 (B) and MS of m/z 221 (C) of the 3-acyl isomer 1a; EI mass spectrum (D), MS of m/z
2
3
2
3
98 (E) and MS of m/z 221 (F) of the 4-acyl isomer 2a; EI mass spectrum (G), MS of m/z 298 (H) and MS of m/z 221 (I) of the 6-acyl isomer 3a

4
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BEGALA ET AL.
2
2
2
FIGURE 3 EI mass spectrum (A), MS of m/z 343 (B) and MS of m/z 221 (C) of the 3-acyl isomer 1b; EI mass spectrum (D), MS of m/z
3
3
2
3
43 (E) and MS of m/z 221 (F) of the 4-acyl isomer 2b; EI mass spectrum (G), MS of m/z 343 (H) and MS of m/z 221 (I) of the 6-acyl isomer 3b
2
3
2
FIGURE 4 EI mass spectrum (A), MS of m/z 343 (B), MS of m/z 266 (C) and MS of m/z 326 (D) of the 3-acyl isomer 1c; EI mass spectrum
(
2
3
2
3
E), MS of m/z 343 (F) and MS of m/z 266 (G) of the 4-acyl isomer 2c; EI mass spectrum (H), MS of m/z 343 (I) and MS of m/z 266 (J) of the
-acyl isomer 3c
6
1
8
[
O]-Benzoyl chloride was prepared by acid-catalyzed hydrolysis
3
|
RESULTS AND DISCUSSION
18
18
(
HCl/H
2
O) of benzonitrile and treatment of [ O]-benzoic acid with
18
thionyl chloride as described by Wnuk and co-workers.
3.1
|
Separation and differentiation of isomers 1a–
Compounds 1d and 1e were obtained by the reaction of
3a
2
4
-(4-methoxybenzyloxy)benzyltriphenylphosphomium bromide and
15
-nitrobenzoyl chlorides in the presence of Et
3
N in toluene.
The total ion current chromatogram of the reaction products from the
Friedel–Crafts acylation of 2-phenylbenzofuran with benzoyl chloride
is reported in Figure 1A. The three isomers so obtained are well
separated, and the ion intensities of the isomers are different from
each other. After purification, we found that acylation leads
predominantly to the 3-acyl isomer 1a together with traces of the
All benzoylbenzofuran isomers and the labeled derivatives were
13
1
isolated and characterized using C NMR and H NMR as described
14–16
in the supporting information and in previous reports.
a, 2ad , 2b and 2c were further purified using high-performance
liquid chromatography.
Isomers
2
5

BEGALA ET AL.
5 of 8
(
Figure 2B) and it is absent in the MS/MS spectra of 2a and 3a
Figures 2E and 2H). Instead, 2a and 3a display the ion at m/z 221 as
(
the base peak, which is particularly weak for the 3-benzoyl isomer 1a.
•
This ion corresponds for all isomers to the loss of radical C
H
6 5
from
the benzoyl group, as supported by the mass shift to m/z 226 in the
spectra of the deuterium analogues 1ad –3ad (Figures S1 and S2).
5
5
Therefore, in the structure of the fragment ion at m/z 221, the
positional information of the carbonyl group on the benzofuran
scaffold is still preserved. Accordingly, further differences in ion
3
abundances were evidenced in the MS spectra of the m/z 221 ions
(
Figures 2C, 2F and 2I): although all isomers exhibit the loss of CO
n
18
SCHEME 2 MS fragmentation pathways for compound 1c
O
molecules (m/z 193) followed by the typical abstraction of further CO
19
from the 2-phenylbenzofuran nucleus (m/z 165), only for isomer 1a
does the ion at m/z 165 constitute the base peak (Figure 2C), whereas
the ion at m/z 193 is the major peak for isomers 2a (Figure 2F) and 3a
(
Figure 2I).
3
.2
|
Separation and differentiation of isomers 1b–
3
b
The total ion current chromatogram of the Friedel–Crafts acylation of
-phenylbenzofuran with 4-nitrobenzoyl chloride is shown in
Figure 1B. The most abundant peak corresponds to the 3-acyl isomer
b, whereas the lower intensity peaks at t of 24.45 and 26.54 min
2
1
R
correspond to the 4- and 6-acyl isomers 2b and 3b, respectively. The
mass spectra of isomeric compounds 1b–3b, despite some minor
differences in relative abundances of fragment ions, are nearly
identical (Figures 3A, 3D and 3G). Each isomer decomposes by the
typical alpha cleavage to the carbonyl group, to afford the loss of the
4
1
-nitrophenyl group (m/z 221) and the 4-nitrobenzoyl cation (m/z
50). Conversely, the MS/MS experiments performed on the
n
18
SCHEME 3 MS fragmentation pathways for compound 1c
O
molecular ions at m/z 343 are effective for differentiating the
-benzoyl isomer 1b from the other two, 2b and 3b (Figures 3B, 3E
3
and 3H). Under this condition the 3-benzoyl isomer 1b leads to the
+
4
-benzoyl isomer 2a and a larger amount of the 6-benzoyl isomer 3a.
All isomers exhibit very similar EI mass spectra (Figures 2A, 2D and
G). The main fragmentation pathways lead to ions at m/z 221, 105
ions at m/z 342 and 296 attributed to the [M − H] and the [M − H
+
•
− NO
2
]
ions, respectively. Both ions are particularly intense in the
2
mass spectrum of 1b, whereas they are weak in the mass spectra of
isomers 2b and 3b, reasonably because the carbonyl group is too far
from the 2-phenyl ring to promote the initial H• loss (discussed
above). Unlike 1b, both isomers 2b and 3b exhibit the ion at m/z
and 77. Only the mass spectrum of isomer 1a shows a unique
diagnostic ion at m/z 297 owing to the loss of radical hydrogen
(
Figure 2A). The hydrogen loss is a typical behavior of 3-acyl isomers
3
as it is the result of the interaction between the 3-carbonyl group
221 as base peak. MS experiments on the m/z 221 ion allow for
16
with the neighboring phenyl ring in the 2-position. In the case of
additional differentiation of 1b from 2b and 3b (Figures 3C, 3F and 3I).
+
isomers 2a and 3a, the [M − H] ion is not observed reasonably
because the distances between the carbonyl group and the 2-phenyl
ring are much greater than in the 3-benzoyl isomer 1a, thus avoiding
3.3
3c
|
Separation and differentiation of isomers 1c–
2
their interaction. MS experiments performed on the molecular ion at
m/z 298 and on the m/z 221 ion of 1a–3a evidenced further
distinctive fragmentation patterns making the 3-acyl isomer (1a) well
recognizable from the other two (Figure 2). On the contrary, the
The Friedel–Crafts acylation of 2-(4-nitrophenyl)benzofuran with
benzoyl chloride leads to a mixture of regioisomers where the desired
3-acyl derivative is formed as a minor product (Figure 1C). The EI mass
spectra of the nitrobenzoyl isomers 1c–3c (Figures 4A, 4E and 4H)
show a rather similar mass fragmentation behavior, i.e. the formation of
4
-benzoyl isomer (2a) and the 6-benzoyl isomer (3a) remained
indistinguishable. In the MS/MS spectrum of the m/z 298 ion, the
+
diagnostic [M − H] ion (m/z 297) is even more favored for isomer 1a

6
of 8
BEGALA ET AL.
the benzoyl cation at m/z 105, and the characteristic loss of the phenyl
ring (m/z 266). Under MS/MS experiments the molecular ions (m/z
m/z 266 ion, favored for 2c and 3c, is practically suppressed. Instead,
the m/z 343 ion exhibits the ion at m/z 342 as the main peak and the ion
•
3
43) of regioisomers 2c and 3c behave quite differently from that of
at m/z 326 due to the elimination of OH radical (see below).
•
+
the 3-acyl isomer 1c as they exhibit the loss of radical C
H
6 5
from the
The lack of the [M − OH] ion in the MS/MS spectrum of the
benzoyl group as the main peak (m/z 266). Interestingly, only in this
2
nitro isomer 1b (Figure 3B) clearly suggests that, when the NO group
series of isomers can the 4-acyl isomer be differentiated from the
is on the 2-phenyl ring, it may play an essential role in the hydroxyl
3
•
6
-acyl isomer through MS experiments on the m/z 266 ion: both
radical loss. A previous study showed that the loss of OH occurred in
2
isomers exhibit the loss of nitrogen dioxide (NO ) to form the m/z
the mass spectrum of 3-benzoyl-2-phenylbenzofuran bearing nitro
16
2
20 ion as the base peak, whereas only for the 4-acyl isomer 2c are the
groups on both phenyl rings. However, it was not possible to verify
•
ions at m/z 238 (83%) and 210 (16%) particularly intense allowing
differentiation from the 6-acyl isomer 3c (m/z 238, 16%; m/z 210, 3%)
if the source of the OH loss was the nitro group, through a chalcone-
20
like mechanism, the oxygen of the carbonyl or both groups. Since
the pathways that lead to the loss of OH remained an opened
question in the previous study, further experiments were undertaken
in the present work.
(
Figures 4G and 4J; Scheme 2). The statistical significance of
differences between the relative intensities of ions at m/z 210 and
2
38 between 2c and 3c was confirmed by Welch's t-test (p < 0.0001).
The 3-acyl isomer 1c can be easily identified and differentiated
3
+
MS experiments performed on the [M − OH] ion from isomer
•
from 2c and 3c on the bases of MS/MS experiments on the molecular
1c (m/z 326) activate, together with the loss of NO (m/z 296), the
•
ion (Figures 4B, 4F and 4I). Under these conditions, the formation of the
loss of NO
2
(m/z 280), which demonstrates that the oxygen involved
2
FIGURE 5 EI mass spectrum (A), MS of m/z
3
3
3
45 (B), MS of m/z 326 (C) and MS of m/z
18
3
28 (D) of the labelled 3-acyl isomer 1c
O

BEGALA ET AL.
7 of 8
2
3
2
FIGURE 6 EI mass spectrum (A), MS of m/z 373 (B) and MS of m/z 356 (C) of the isomer 1d; EI mass spectrum (D) and MS of m/z
3
73 (E) of the isomer 1e
•
in the OH loss arises, at least in part, from the carbonyl group
MS/MS conditions only the 3-(4-methoxybenzoyl)-2-(4-nitrophenyl)
•
(
Figure 4D; Scheme 3). This behavior is of particular interest as there
benzofuran 1d (m/z 373) displays the loss of OH radical generating
•
3
are only few reports of the involvement of a carbonyl oxygen atom in
the ion at m/z 356 (Figure 6B) that further loses NO
2
under MS
2
1–24
the formation of dehydroxylated ions.
experiments to form ion at m/z 310 (Figure 6C). Conversely, the
2-(4-methoxyphenyl)-3-(4-nitrobenzoyl)benzofuran 1e does not show
Some experiments were also performed on the analogous
18
18
•
3
-benzoyl-2-(4-nitrophenyl)benzofuran 1c[ O] labeled with O at
the OH loss (Figures 6D and 6E), unequivocally proving the lack of
2
the carbonyl group (Figure 5; Scheme 3). The MS experiments
the 3-benzoyl-2-(4-nitrophenyl)benzofuran nucleus in its structure.
performed on the molecular ion at m/z 345 showed the formation of
1
8
+
+
[
M − OH] ion at m/z 326 and of [M − OH] ion at m/z
•
3
28 (Figure 5B). These data prove that the OH loss arises from the
4
|
CONCLUSIONS
oxygen of both groups. This conclusion is corroborated by the losses
•
•
18
+
of NO and NO
2
from the [M − OH] ion (m/z 326), and by the
Regioisomeric mixtures of 3-, 4- and 6-benzoyl-2-phenylbenzofurans
are obtained by Friedel–Crafts acylation of 2-phenylbenzofurans.
GC/MS can be used for the rapid separation and identification of
3-benzoyl-2-phenylbenzofurans from their 4- and 6-benzoyl
regioisomers directly in the crude reaction mixtures without the need
•
+
3
loss of NO from the [M − OH] ion (m/z 328) under MS
experiments (Figures 5C and 5D; Scheme 3). Interestingly, the
intensity of the m/z 326 ion is significantly higher than that of the m/z
3
28 ion (relative intensity 47% versus 15%), thus demonstrating that
n
the oxygen of the carbonyl group contributes more significantly to
of reference standards. EI-MS experiments on the molecular ions yield
•
•
the OH loss. However, when the source of OH loss is exclusively
the carbonyl group, such as in the case of the unsubstituted
specific fragments which arise from the interaction of the 3-benzoyl
+
+
group with the neighbor 2-phenyl ring, i.e. [M − H] and [M − OH]
+
compound 1a, the intensity of the [M − OH] ion is very low (m/z
ions, nearly absent in the mass spectra of the other regioisomers. These
diagnostic ions indicate that the benzoyl group is located in the
3-position of the 2-phenylbenzofuran skeleton. 3-Acyl isomers
2
81, relative intensity 3%; Figure 2B). These data suggest that the
•
OH loss is significantly increased by the presence of the nitro group
+
on the 2-phenyl ring, not only because the NO
2
group can itself
containing nitro group in their skeleton display abundant [M − OH]
•
eliminate radical OH , but also because it has an essential influence
ions (relative intensity > 40) only when the nitro group is located on the
2-phenyl ring. We hypothesize that this behavior could be expanded to
derivatives that possess the 4-nitrochalcone (Ar&bond;[C&dbond;O]
•
on the OH elimination from the carbonyl group.
+
To show that the [M − OH] ion functions as a structurally
diagnostic product ion for the identification of the 3-benzoyl-
6 4 2
&bond;C&dbond;C&bond;C H NO ) structural fragment.
2
-(4-nitrophenyl)benzofuran nucleus, we examined the mass spectra
The 4- and 6-benzoyl regioisomers, unsubstituted on the
2-phenyl ring, show an identical mass spectrometric behavior, even
1
5
of two isomeric nitro derivatives 1d and 1e (Figure 6). Under

8
of 8
BEGALA ET AL.
n
under MS experiments. 4-Benzoyl-2-nitrophenyl regioisomer 2c
13. March RM, Todd JFJ (Eds). Practical Aspects of Ion Trap Mass
Spectrometry. Vol. 1. CRC Press; 1995.
+
displays a specific mass spectrometric behavior of the [M − Ar]
1
4. Begala M, Caboni PL, Matos MJ, Delogu GL. Unexpected one-step
synthesis of 3-benzoyl-2-phenylbenzofurans under Wittig conditions.
Tetrahedron Lett. 2018;59(18):1711-1714. https://doi.org/10.1016/j.
tetlet.2018.03.048
fragment ion which allows the distinction from its 6-benzoyl-
2
-nitrophenyl regioisomer 3c.
1
5. Begala M, Mancinelli M, Delogu GL. Unexpected migration of a
benzoyl group in the intramolecular Wittig reaction of o-
acyloxybenzylidenephosphoranes with benzoyl chlorides: One-pot
synthesis of isomeric 3-benzoyl-2-phenylbenzofurans. Tetrahedron
Lett. 2020;61:151634. https://doi.org/10.1016/j.tetlet.2020.151634
6. Begala M, Delogu GL. Unexpected detection of 3-aroylbenzofuran
side products in the preparation of 2-arylbenzofurans: Identification,
ACKNOWLEDGMENTS
The present work was partially supported by FIR (Fondo Integrativo
per la Ricerca – annualità 2018 and 2019), University of Cagliari.
1
PEER REVIEW
The peer review history for this article is available at https://publons.
com/publon/10.1002/rcm.9082.
characterization, and comparison with chalcone's fragmentation
n
patterns using EI/MS .
J Mass Spectrom. 2019;54(9):750-760.
https://doi.org/10.1002/jms.4425
7. Hercouet A, Le Corre
ORCID
1
1
M.
Etude
des
ω
Michela Begala
Michele Mancinelli
Elias Quezada
https://orcid.org/0000-0002-8213-2335
https://orcid.org/0000-0002-8499-5265
https://orcid.org/0000-0002-8750-170X
acyloxybenzylidènetriphénylphosphoranes. Nouvelle voie d'accès aux
benzofurannes. Tetrahedron. 1981;37(16):2867-2873. https://doi.
org/10.1016/S0040-4020(01)92357-9
8. Wnuk SF, Chowdhury SM, Garcia PI Jr, Robins MJ. Stereodefined
Giovanna Lucia Delogu
https://orcid.org/0000-0003-0307-1544
0
0
17
0
0
synthesis of O3 -labeled uracil nucleosides. 3 -[ O]-2 -Azido-2 -
0
deoxyuridine 5 -diphosphate as
a probe for the mechanism of
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