Synthesis and stability of strongly acidic benzamide derivatives

Article abstract of DOI:10.3762/bjoc.14.38

Reactivity studies of strong organic acids based on the replacement of one or both of the oxygens in benzoic acids with the trifluoromethanesulfonamide group are reported. Novel derivatives of these types of acids were synthesized in good yields. The gene

Full text of DOI:10.3762/bjoc.14.38

Synthesis and stability of strongly acidic
benzamide derivatives
Frederik Diness*1,2, Niels J. Bjerrum3 and Mikael Begtrup1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2018, 14, 523–530.
1Department of Drug Design and Pharmacology, University of
Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark,
2Present address: Department of Chemistry, University of
Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark
and 3Department of Energy Conversion and Storage, Technical
University of Denmark, Kemitorvet, Building 207, room 042, DK-2800
Kgs. Lyngby, Denmark
doi:10.3762/bjoc.14.38
Received: 17 December 2017
Accepted: 13 February 2018
Published: 27 February 2018
This article is part of the Thematic Series "Organo-fluorine chemistry IV".
Guest Editor: D. O'Hagan
Email:
Frederik Diness* - fdi@chem.ku.dk
© 2018 Diness et al.; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
benzoic acid; cross-coupling; hydrolysis; SNAr;
trifluoromethanesulfonamide
Abstract
Reactivity studies of strong organic acids based on the replacement of one or both of the oxygens in benzoic acids with the trifluo-
romethanesulfonamide group are reported. Novel derivatives of these types of acids were synthesized in good yields. The gener-
ated N-triflylbenzamides were further functionalized through cross-coupling and nucleophilic aromatic substitution reactions. All
compounds were stable in dilute aqueous solutions. Studies of stability under acidic and basic conditions are also reported.
Introduction
Very strong organic acids are interesting as catalysts for chemi- (Figure 1). In contrast, halogenated benzoic acid derivatives are
cal reactions [1,2] and for facilitation of proton conduction [3]. easily functionalized through cross-coupling [4,5] or nucleo-
In order to enable their incorporation into functional materials philic aromatic substitution reactions (SNAr) [6,7]. Benzoic
(e.g., polymers), these acids need additional functionality in the acids (e.g., 2) are relatively weak acids, even with highly elec-
form of a reactive group, and the chemistry applied for functio- tron-withdrawing substituents on the aromatic core [8]. Very
nalization must be compatible with their strong acidic nature. strong benzoic acid derivatives (e.g., 4 and 6) have been synthe-
Many types of strong organic acids such as triflic acid (7) or tri- sized by replacing one or both of the oxygens of the carboxyl-
fluoroacetic acid (3) are not readily modified, and changing ate group with the trifluoromethanesulfonamide (1) group
substituents on these acids will heavily impact their pKa value [9-11].
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Beilstein J. Org. Chem. 2018, 14, 523–530.
Figure 1: Acid strength (pKa) of various organic acids in acetonitrile or water (nr = not reported) [12-14].
Interestingly, these types of compounds have attracted little [26-33]. Finally, two examples of syntheses via palladium-cata-
attention and have not thoroughly been explored with regards to lyzed carbonylation of trifluoromethanesulfonamide (1) have
their applications. Few publications report the application of been reported [34,35]. The N-triflylbenzamides have only been
N-triflylbenzamides as benzoic acid bioisosteres in receptor explored as substrates in a few reactions. A recent report de-
antagonists and enzyme inhibitors (Figure 2) [15-18]. scribes using N-triflylbenzamide as a directing group in a ruthe-
The reported derivatives all displayed activity, but only with nium-catalyzed C–H activation reaction [36]. Most other re-
similar or reduced potency compared to the corresponding ported transformations pass via the imidoyl chloride intermedi-
benzoic acid derivatives. Application of deprotonated ates (equivalent to 10) to the amidine derivatives, which have
N-triflylbenzamide derivatives as counter anions in been used in rearrangement reaction studies [9,37-39]. By these
supramolecular crown ether compounds for metal ion extrac- means also N,N’-bis(triflyl)benzimidamides (also termed benz-
tion has also been reported by one group (Figure 2) amidines) have been generated, but only one report describes
[19-25]. All the N-triflylbenzamide constructs generated their syntheses [10]. The N-triflylbenzamides are stronger acids
for this purpose have proved superior to the corresponding than any of the carboxylic acids, including trifluoroacetic acid
benzoate derivatives with regards to metal ion extraction capa- (3). The N,N’-bis(triflyl)benzimidamides are very strong
bility.
organic acids, much stronger than p-toluenesulfonic acid (5)
which is commonly used as a soluble organic acid catalyst in
chemical reactions. Remarkably, neither the N-triflylbenz-
amides nor the N,N’-bis(triflyl)benzimidamides have been
studied as Brønsted acid catalysts. Their chemical stability in-
cluding compatibility with conditions applied to common chem-
ical transformations has not been described. With the prospect
of using these strong benzoic acid derivatives for enhancing
proton conductivity in proton-exchange membrane (PEM) fuel
cells [3,40] we have examined their compatibility with chemi-
cal transformations as well as their stability towards hydrolytic
conditions.
The N-triflylbenzamides are simple to generate by the reaction
between trifluoromethanesulfonamide (1) and an activated
benzoyl derivative such as benzoyl chlorides (e.g., 8a,
Scheme 1) [9,15]. The reactions are generally high yielding and
the products are simple to isolate in their protonated form by
recrystallization. The generation of N-triflylbenzamides by
direct reaction of various triflyl derivatives with benzamides or
benzoic acids has been less systematically explored. Most com-
pounds synthesized by these approaches are N-alkylated or
N-arylated and have been formed unintentionally as byproducts
Figure 2: Examples of functional molecules containing an N-triflylbenzamide.
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Scheme 1: Synthesis of the strongly acidic benzamide derivatives.
Results and Discussion
only compound 14. This is in line with previous observations of
In these studies, four substituted N-triflylbenzamides 9a–d were SNAr reactions on pentafluorobenzene derivatives [42]. Due to
synthesized by the reaction of the corresponding benzoyl chlo- the zwitterionic nature of the products, reversed-phase chroma-
ride with trifluoromethanesulfonamide (1, Scheme 1). The tography was chosen to simplify the purifications.
known 4-fluoro-N-triflylbenzamide (9a) was synthesized ac-
cording to the previously reported method [9] and with few
adjustments this methodology was also applied for the genera-
tion of three new derivatives 9b–d, which were obtained in
good yields. The 4-bromo derivative 9d was further converted
into the N,N’-bis(triflyl)benzimidamide 12 by formation of the
corresponding imidoyl chlorides 10 with PCl5 in POCl3, fol-
lowed by the additional reaction with trifluoromethanesulfon-
amide (1) and protonation by sulfuric acid (Scheme 1) [10].
In recent years, we have reported high yielding catalyst-free
N-arylation by SNAr reaction of mono- or perfluorobenzene de-
rivatives [41-43]. Hence, it was proposed that the 4-fluoro and
the pentafluorobenzamide derivatives 9a and 9c could be func-
tionalized through SNAr reactions. Thus, compounds 9a and 9c
were reacted with benzimidazole under previously developed
conditions (Scheme 2) [41,42]. The benzimidazole was chosen
Scheme 2: SNAr reactions of fluoro-substituted benzamide derivatives.
as model nucleophile for polybenzimidazole, a polymer com-
monly applied as a membrane in PEM fuel cells [40]. These
reactions provided the 4-benzimidazolyl derivatives 13 and 14 The N-triflylbenzamide group also proved stable to cross-
in good yields and the N-triflylbenzamide group proved to be coupling reaction conditions, as exemplified by a
stable under these reaction conditions. Gratifyingly it was palladium-catalyzed Suzuki–Miyaura reaction of the 4-bromo-
possible to perform selective mono-substitution of the penta- substituted derivative 9d (Scheme 3). The corresponding N,N’-
fluoro derivative regioselectively in the 4-position, affording bis(triflyl)benzimidamide derivative 12 was also tested under
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Beilstein J. Org. Chem. 2018, 14, 523–530.
Scheme 3: Cross-coupling reactions of N-triflylbenzoic acid derivatives.
identical conditions. The reaction proceeded with high conver- pounds also remained fully intact in 0.5 M aqueous NaOH. In
sion, but surprisingly the major product of this reaction was also solutions of 0.5 M aqueous HCl the compounds very slowly
the N-triflylbenzamide 15. Additional experiments revealed that degraded over weeks. The N,N’-bis(triflyl)benzimidamide 12
the N,N’-bis(triflyl)benzimidamide group was unstable in was also stable in dilute aqueous solutions and was even more
aqueous basic conditions.
stable in 0.5 M aqueous HCl than the corresponding N-triflyl-
benzamide 9d. Hence, in the acid-catalyzed hydrolysis reaction
This led to concerns about the stability of the products in of 12 the 4-bromo-N-triflylbenzamide (9d) was only detected as
general. In addition, during characterization by NMR it was a trace as 9d converted faster to 4-bromobenzoic acid than com-
also noted that some samples of the N-triflylbenzamide prod- pound 12 converted to 9d. In contrast, 0.5 M aqueous NaOH
ucts contained small amounts of the parent benzoic acid, despite rapidly hydrolyzed the N,N’-bis(triflyl)benzimidamide 12 to
prior purification by recrystallization. Further studies revealed yield the base-stable N-triflylbenzamide 9d.
that the content of benzoic acid increased over time in the solu-
tions and the conversion rate was concentration dependent, the Neither the mono-substituted N-triflylbenzamides 9a and 9b nor
reason being simple hydrolysis auto-catalyzed by the acids the 4-bromo-N,N’-bis(triflyl)benzimidamide (12) were stable in
themselves. This phenomenon was also observed for N,N’- heated methanolic phosphoric acid, which is commonly used
bis(triflyl)benzimidamide 12 but at slower rate. Hence, an elab- for operating PEM fuel cells (Figure 3) [44]. However, most
orated study of the products’ stability towards acid or base surprisingly, the pentafluoro N-triflylbenzamide (9c) was found
promoted hydrolysis was undertaken (Scheme 4). Dilute to be much more stable under these conditions, which is
aqueous solutions (0.5 mg/mL) of the N-triflylbenzamides promising for future applications in proton conducting materi-
displayed no sign of degeneration even after 24 h. The com- als.
Scheme 4: Hydrolysis rates of the 4-bromobenzoic acid derivatives.
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Beilstein J. Org. Chem. 2018, 14, 523–530.
Figure 3: Content (percent) of super acids (0.5 mg/mL) over time (hours) in H3PO4/H2O/MeOH 17:3:20 at 50 °C.
Conclusion
filtered and the solvent was removed from the filtrate. The
In summary, it has been demonstrated that novel mono- or bis- crude product was mixed with 50% H2SO4 (aq, 50 mL) and the
trifluoromethanesulfonamide derivatives of benzoic acids bear- mixture stirred for 30 min. The precipitate was isolated and
ing a reactive group (bromine or fluorine) may be generated in dried overnight. The product was purified by recrystallization
good yields and further functionalized through nucleophilic aro- from toluene.
matic substitution or cross-coupling reactions. It was found that
the products were stable in dilute aqueous solutions, but they
slowly hydrolyzed in concentrated solutions or in the presence
of other strong acids. The N-triflylbenzamides 9a–d were
stable in basic aqueous solutions whereas the tested bromo-
N,N’-bis(triflyl)benzimidamide 12 rapidly hydrolyzed to the
corresponding bromo-N-triflylbenzamide 9d. Under conditions
simulating ambient PEM fuel cells operation the 4-substituted
benzamide derivatives 9a,b,d and 12 were about 50%
degraded within 24 h, whereas the pentafluoro N-triflylbenz-
amide (9c) under the same conditions was less than 5%
degraded.
4-Fluoro-N-((trifluoromethyl)sulfonyl)benzamide (9a) [9]:
Synthesized by general procedure. The product was obtained as
small clear crystalline flakes (1.88 g, 69%). mp 152–154 °C;
1H NMR (500 MHz, methanol-d4) δ 7.99 (dd, J = 9.0, 5.2 Hz,
2H), 7.29 (t, J = 8.8 Hz, 2H); 13C NMR (126 MHz, methanol-
d4) δ 167.6 (d, J = 254.3 Hz), 166.0, 132.8 (d, J = 9.6 Hz),
129.1 (d, J = 3.1 Hz), 121.0 (q, J = 321.5 Hz), 117.1 (d, J = 22.7
Hz); 19F NMR (470 MHz, methanol-d4) δ −76.93 (s, 3F),
−105.75 (s, 1F); HRMS (TOF) m/z: [M − H]− calcd for
C8H4F4NO3S−, 269.9854; found, 269.9888.
4-Trifluoromethyl-N-((trifluoromethyl)sulfonyl)benzamide
(9b): Synthesized by general procedure. The product was ob-
tained as white powder (2.83 g, 88%). mp 174–179 °C;
Experimental
General aspects
All purchased chemicals were used without further purification. 1H NMR (500 MHz, methanol-d4) δ 8.09 (d, J = 8.0 Hz, 1H),
All solvents were HPLC grade. NMR data were recorded on a 7.86 (d, J = 8.1 Hz, 1H); 13C NMR (126 MHz, methanol-d4)
Bruker 500 MHz spectrometer at 298 K with methanol-d4, δ 166.3, 136.5, 136.0 (q, J = 32.6 Hz), 130.6, 127.0 (q, J = 4.0
DMSO-d6 or hexafluorobenzene as internal standard. High- Hz), 125.0 (q, J = 271.9 Hz), 121.0 (q, J = 321.5 Hz); 19F NMR
resolution mass spectrometry (HRMS) was performed on a (470 MHz, methanol-d4) δ −64.31 (s, 3F), −77.06 (s, 3F);
Bruker MALDI–TOF spectrometer.
HRMS (TOF) m/z: [M − H]− calcd for C9H4F6NO3S−,
319.9822; found, 319.9869.
General procedure
Benzoyl chloride (10.0 mmol) in Et2O (10 mL) was added Pentafluoro-N-((trifluoromethyl)sulfonyl)benzamide (9c):
dropwise to a solution of trifluoromethanesulfonamide (1.5 g, Synthesized by general procedure. The product was obtained as
10.0 mmol) and triethylamine (3.5 mL, 25 mmol) in Et2O clear needle-shaped crystal (2.40 g, 70%). mp 129–131°C;
(30 mL) at 0 °C over 10 min. The mixture was stirred for 13C NMR (126 MHz, methanol-d4) δ 158.6, 145.4 (dm,
30 min and then heated to reflux for 2 h. The reaction was J = 257.0 Hz), 144.5 (dm, J = 256.8 Hz), 139.1 (dm, J = 250.0
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Beilstein J. Org. Chem. 2018, 14, 523–530.
Hz), 121.0 (q, J = 321.4 Hz), 111.9 (t, J = 17.6 Hz); 19F NMR δ 170.1, 137.6, 132.23, 131.9, 127.6, 121.02 (q, J = 319.3 Hz);
(470 MHz, methanol-d4) δ −78.15 (s, 3F), −142.78 (d, J = 17.9 19F NMR (470 MHz, MeOD) δ −80.60 (s); HRMS (TOF) m/z:
Hz, 2F), −152.25 (t, J = 19.2 Hz, 1F), −162.65 (t, J = 18.3 Hz, [M − H]− calcd for C9H479BrF6N2O4S2−, 460.8706; found.
2F); HRMS (TOF) m/z: [M − H]− calcd for C8F8NO3S−, 460.8766.
341.9477; found, 341.9520.
4-(1H-Benzo[d]imidazol-1-yl)-N-((trifluoromethyl)sul-
4-Bromo-N-((trifluoromethyl)sulfonyl)benzamide (9d): Syn- fonyl)benzamide (13): Cesium carbonate (163 mg, 5 equiv)
thesized by general procedure. The product was obtained as was added to a glass vial containing benzimidazole (17.7 mg,
white powder (2.98 g, 90%). mp 156–158 °C; 1H NMR 1.5 equiv) and 4-fluoro-N-((trifluoromethyl)sulfonyl)benz-
(500 MHz, methanol-d4) δ 7.83 (d, J = 8.8 Hz, 2H), 7.73 (d, amide (9a, 27.1 mg, 0.1 mmol) in dry dimethylacetamide
J = 8.7 Hz, 2H); 13C NMR (126 MHz, methanol-d4) δ 166.5, (1.0 mL). The reaction was heated to 120 °C for 12 h. The reac-
133.3, 131.9, 131. 6, 129.9, 121.0 (q, J = 321.5 Hz); 19F NMR tion was quenched with 1.0 M HCl (aq, 100 μL) and the sol-
(470 MHz, MeOD) δ −77.00 (s); HRMS (TOF) m/z: vent removed in vacuo. The crude product was dissolved in
[M − H]− calcd for C8H479BrF3NO3S−, 329.9053; found, acetonitrile/water 1:1 and filtered through a Teflon syringe
329.9095.
filter. The solution was transferred to a C18 gel column and
purified by vacuum liquid chromatography (VLC, 0 to 90%
Triethylamine salt of 4-bromo-N,N'-bis((trifluoromethyl)- CH3CN in 0.01 M HCl). After lyophilization the product was
sulfonyl)benzimidamide (11): 4-Bromo-N-((trifluoromethyl)- obtained as a white powder (17 mg, 46%). 1H NMR (500 MHz,
sulfonyl)benzamide (9d, 1.68 g, 5.0 mmol) was mixed with DMSO-d6) δ 9.64 (s, 1H), 8.20 (d, J = 8.5 Hz, 2H), 7.99–7.90
POCl3 (3 mL) and PCl5 (1.11 g). The reaction mixture was (m, 1H), 7.81 (d, J = 8.5 Hz, 3H), 7.64–7.53 (m, 2H), 4.53 (s,
stirred at rt for 2 h and then at 50 °C for 30 min. The solvent 2H); 13C NMR (126 MHz, DMSO-d6) δ 168.5, 142.3, 138.4,
was removed and the imidoyl chloride was recrystallized from 136.0, 134.8, 131.4, 130.3, 126.0, 125.6, 124.0, 120.3 (q,
heptane (1.71 g, 98%). The imidoyl chloride (1.06 g) was dis- J = 324.8 Hz), 116.6, 112.6; 19F NMR (470 MHz, DMSO-d6)
solved in dry acetonitrile (4 mL) and the solution was added δ −79.75 (s); HRMS (TOF) m/z: [M − H]− calcd for
dropwise to a mixture of trifluoromethanesulfonamide (450 mg) C15H9F3N3O3S−, 368.0322; found, 368.0367.
and triethylamine (0.85 mL) in dry acetonitrile (8 mL) at 0 °C.
The mixture was stirred at 0 °C for 30 min and then at rt for 5 h. 4-(1H-Benzo[d]imidazol-1-yl)-2,3,5,6-tetrafluoro-N-((trifluo-
The solvent was removed in vacuo and the residue was mixed romethyl)sulfonyl)benzamide (14): Sodium tert-butoxide
with CH2Cl2 (30 mL) and 10% HCl (aq, 50 mL). The organic (21 mg, 2.2 equiv) was added to a glass vial containing benz-
phase was separated and the water phase was extracted with imidazole (11.8 mg, 0.1 mmol) in dry dimethylacetamide
CH2Cl2 (30 mL). The combined organic phase was washed (1.0 mL). The mixture was stirred at rt for 1 min. The mixture
with saturated NaHCO3 (aq) and dried with MgSO4. The sol- was cooled to 0 °C and added to a solution of 9c (37.7 mg,
vent was removed in vacuo and the product was isolated as 0.11 mmol) in dry dimethylacetamide (1.0 mL) under stirring at
white powder (1.58 g, 93%). 1H NMR (500 MHz, methanol-d4) 0 °C. The reaction was allowed to reach rt and stirred for 1 h.
δ 7.73 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.6 Hz, 2H), 3.20 (q, The reaction was quenched with 1.0 M HCl (aq, 20 μL) and the
J = 7.3 Hz, 6H), 1.30 (t, J = 7.3 Hz, 9H); 13C NMR (126 MHz, solvent removed in vacuo. The crude product was dissolved in
methanol-d4) δ 170.0, 137.8, 132.3, 132.0, 127.6, 121.1 (q, acetonitrile/water 1:1 and filtered through a Teflon syringe
J = 319.2 Hz), 48.0, 9.3; 19F NMR (470 MHz, MeOD) δ −80.67 filter. The solution was transferred to a C18 gel column and
( s ) ; H R M S ( T O F ) m / z : [ M
− H ] − c a l c d f o r purified by vacuum liquid chromatography (VLC, 0 to 90%
C9H479BrF6N2O4S2−, 460.8706; found, 460.8769. CH3CN in 0.01 M HCl). After lyophilization the product was
obtained as a white powder (30 mg, 81%). 1H NMR (500 MHz,
4-Bromo-N,N'-bis((trifluoromethyl)sulfonyl)benzimidamide DMSO-d6) δ 8.70 (s, 1H), 7.83 (dt, J = 7.3, 3.6 Hz, 1H),
(12): The trimethylamine salt of 4-bromo-N,N'-bis((trifluoro- 7.66–7.57 (m, 1H), 7.47–7.34 (m, 2H); 13C NMR (126 MHz,
methyl)sulfonyl)benzimidamide (11, 0.50 g, 0.89 mmol) was DMSO) δ 161.34, 143.9, 143.6 (dddd, J = 246.1, 13.0, 8.4, 4.1
mixed with H2SO4 (96%, 1.0 mL). The mixture was shaken for Hz), 142.2 (ddm, J = 252.7, 16.4 Hz), 141.3, 137.6 (dm,
30 min and extracted with CH2Cl2 (5 × 6 mL). The extract was J = 254.1 Hz), 133.1, 124.5, 123.6, 121.4 (t, J = 21.9 Hz), 120.0
dried with MgSO4 and the solvent removed in vacuo. The crude (q, J = 323.7 Hz), 119. 5, 114.1 (t, J = 14.6 Hz), 111.3;
product was recrystallized from toluene and heptane to yield 12 19F NMR (470 MHz, DMSO-d6) δ −80.53 (s), −145.56 (dd,
as a white crystalline powder (367 mg, 0.79 mmol, 89%). J = 25.2, 12.3 Hz), −148.81 (dd, J = 24.1, 11.3 Hz); HRMS
1H NMR (500 MHz, methanol-d4) δ 7.72 (d, J = 8.7 Hz, 2H), (TOF) m/z: [M − H]− calcd for C15H5F7N3O3S−, 439.9945;
7.59 (d, J = 8.6 Hz, 2H); 13C NMR (126 MHz, methanol-d4) found, 434.0006.
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Beilstein J. Org. Chem. 2018, 14, 523–530.
6. Dehe, D.; Munstein, I.; Reis, A.; Thiel, W. R. J. Org. Chem. 2011, 76,
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4'-Methoxy-N-((trifluoromethyl)sulfonyl)-[1,1'-biphenyl]-4-
carboxamide (15): Palladium(II) acetate (6 mg, 27 μmol), tri-
phenylphosphine (20 mg, 76 μmol) and H2O (0.5 μL, 28 μmol)
were mixed in degassed dimethylacetamide (1.0 mL). The cata-
lyst was preformed by heating the mixture in a closed screw cap
vial to 100 °C for 1 min (color changed from yellow to deep
red). A part of the catalyst mixture (0.2 mL) was added to a
microwave glass vial containing a degassed mixture of 9d
(33.1 mg, 0.1 mmol), 4-methoxyphenylboronic acid (22.8 mg,
0.15 mmol, 1.5 equiv) and cesium carbonate (100 mg, 3 equiv)
in dimethylacetamide (0.8 mL). The vial was closed with a
teflon cap and heated to 80 °C for 12 h under stirring. The reac-
tion was quenched with 1.0 M HCl (aq, 100 μL) and the sol-
vent removed in vacuo. The crude product was dissolved in
acetonitrile/water 1:1 and filtered through a Teflon syringe
filter. The solution was transferred to a C18 gel column and
purified by vacuum liquid chromatography (VLC, 0 to 90%
CH3CN in 0.01 M HCl). After lyophilization the product was
obtained as a white powder (11 mg, 31%). 1H NMR (500 MHz,
DMSO-d6) δ 7.96 (d, J = 8.3 Hz, 2H), 7.69–7.59 (m, 4H), 7.03
(d, J = 8.8 Hz, 2H), 3.80 (s, 3H); 13C NMR (126 MHz, DMSO-
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Supporting Information
doi:10.1016/j.bmcl.2008.01.058
17.Cervi, G.; Magnaghi, P.; Asa, D.; Avanzi, N.; Badari, A.; Borghi, D.;
Supporting Information File 1
Caruso, M.; Cirla, A.; Cozzi, L.; Felder, E.; Galvani, A.; Gasparri, F.;
NMR spectra of synthesized compounds.
Lomolino, A.; Magnuson, S.; Malgesini, B.; Motto, I.; Pasi, M.; Rizzi, S.;
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-38-S1.pdf]
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18.Althaus, J.; Hake, T.; Hanekamp, W.; Lehr, M.
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Acknowledgements
doi:10.1080/14756366.2016.1178246
The Danish Strategic Research Foundation of Energy and Envi-
ronment is acknowledged for supporting this research (Grant
2104-05-0026). Lundbeck A/S is acknowledged for supporting
research within nucleophilic aromatic substitution reactions.
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