Exploiting the narrow gap of rearrangement between the substituents in the vicinal disubstitution reactions of diaryliodonium salts with pyridine N-sulfonamidates

Article abstract of DOI:10.1039/c4ob01744g

The vicinal disubstitution reactions of diaryliodonium salts with pyridine N-sulfonamidates to give o-pyridinium anilines were fully examined. A reaction pathway of N-arylation occurring at the amidate group followed by a radical rearrangement is proposed. The electronic effects of various substituents in this radical rearrangement were investigated.

Full text of DOI:10.1039/c4ob01744g

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Exploiting the narrow gap of rearrangement
between the substituents in the vicinal
disubstitution reactions of diaryliodonium salts
with pyridine N-sulfonamidates†
Cite this: DOI: 10.1039/c4ob01744g
Yong Wang,a,b Ming Li,*a Lirong Wen,a Peng Jing,b Xiang Sub and Chao Chen*b
Received 14th August 2014,
Accepted 24th October 2014
The vicinal disubstitution reactions of diaryliodonium salts with pyridine N-sulfonamidates to give o-pyri-
dinium anilines were fully examined. A reaction pathway of N-arylation occurring at the amidate group
followed by a radical rearrangement is proposed. The electronic effects of various substituents in this
radical rearrangement were investigated.
DOI: 10.1039/c4ob01744g
www.rsc.org/obc
Introduction
Polysubstituted benzene derivatives are very important com-
pounds in organic chemistry, natural product chemistry,
pharmaceutical chemistry and materials science.1 Conse-
quently, there is a vast and long-term demand for the regio-
selective organic synthesis of benzene derivatives with mul-
tiple substituents. In addition to the assembly of benzene
rings using small acyclic molecules (e.g., Reepe-type reac-
tions),2 more practical and efficient approaches towards poly-
substituted benzene derivatives are traditionally based on
aromatic substitution on the C–H bond, which introduces a
substituent on the given arene with various substitution
effects. A majority of these synthetic methodologies are based
on electrophilic substitution,3 but the additional substituent is
usually introduced at the meta position [when R is an electron
withdrawing group (EWG)] or the para position [when R is an
electron donating group (EDG)] (Scheme 1). Regio-selectively
introducing a substituent on the ortho position of the benzene
ring is less common and more challenging. The use of a
directing group is the main approach to introducing a substi-
tuent at the ortho C–H bond (via ortho-metallation4 or C–H
activation catalyzed by transition metals5), but the scope of
this reaction is highly restricted in nature. The Fries rearrange-
Scheme 1 Various methods of introducing
benzene ring via electrophilic substitution.
X groups on a given
ment is also an efficient and regio-selective way of synthesizing
ortho-substituted benzene derivatives.6
As part of our ongoing interest in the efficient synthesis of
polysubstituted benzene derivatives, we have previously
reported a vicinal disubstitution reaction of diaryliodonium
salts with pyridine N-oxides (reaction 1).8 The reaction pro-
vided a selective technique to introduce two substituents at
the ortho- and ipso-positions of the benzene ring simul-
taneously (reaction 2). Interestingly, this vicinal disubstitution
reaction is also applicable to pyridine N-sulfonamidate,9 where
o-pyridinium aniline is isolated instead. In our previously pub-
lished work,7 a pathway of N-arylation at the amidate group
followed by a radical rearrangement was proposed for the reac-
tion. In this paper the effect of substituents on this radical
rearrangement is reported.
aCollege of Chemistry and Molecular Engineering, Qingdao University of Science &
Technology, Qingdao, 266042, China. E-mail: Chenchao01@mails.tsinghua.edu.cn,
liming928@qust.edu.cn
bKey Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry
of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China
†Electronic supplementary information (ESI) available: Spectra of synthesized
compounds (3, 4, 6a, 6b and 7). CCDC 1008472–1008474. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c4ob01744g
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ð1Þ
ð2Þ
Results and discussion
Arylation of pyridinium sulfonamidates with diaryliodonium
salts
The arylation products of pyridinium sulfonamidates with dia-
ryliodonium salts were prepared to investigate the proposed
rearrangement. It was not possible to isolate the arylation
product 3aa by heating the reaction mixture of 1a and 2a at
130 °C, although a rearrangement reaction producing o-pyridi-
nium aniline occurred. However, when 10 mmol% copper(II)
triflate (Cu(OTf)2) was added, a 57% yield of the arylation
product 3aa was obtained at 75 °C (see ESI† for details). In this
manner, a series of arylation products (3) of 2 with substituted
iodonium salts 1 (Scheme 2) were isolated at good to excellent
yields (Scheme 3). As shown in Scheme 3, the iodonium salts
bearing o-, m-, or p-methyl and 2,4-dimethyl groups all worked
well to give the products 3a–3e. Other iodonium salts with
functional groups including fluoro-, chloro-, bromo- and tri-
fluoro-methyloxyl-groups on a phenyl ring (1f–1n) were also
tolerated in the Cu-catalyzed N-arylation reactions. When
unsymmetrical iodonium salts (1g, 1l and 1m) were used, the
amination took place on the less hindered phenyl ring. Finally,
several substituted pyridinium sulfonamidates were chosen for
the arylation reaction and the corresponding products were
also isolated in good yield. Normal substituents on the pyri-
dine ring did not affect the arylation of the sulfonamidate
group. All the new compounds were characterized by proton
nuclear magnetic resonance (1H-NMR), carbon-13 nuclear
magnetic resonance (13C-NMR), electrospray ionisation-mass
spectrometry (ESI-MS) and high-resolution mass spectrometry
(HRMS). The structure of product 3kb was confirmed by
single-crystal X-ray diffraction (XRD) analysis (Fig. 1).10
Scheme 2 (1) Diaryliodonium salts and (2) pyridinium sulfonamidates
used in the reaction for the preparation of the products (3).
well to give the rearranged product. The structure of 4da was
further demonstrated by single-crystal XRD analysis (Fig. 2).11
The crystal structure clearly shows that the N–N bond was
cleaved and inserted by a phenylene group. In addition, the
ipso position of the iodonium salt was substituted by a tosy-
lamide group and the ortho position was substituted by a pyri-
dinium moiety. When the para substituted R2 was a fluoro- or
chloro-atom, the reaction proceeded smoothly to give the
Rearrangement of arylated pyridinium sulfonamidates
Next the formation of the rearrangement products was investi- expected product. However, when the para substituted R2 was
gated by reacting pyridinium salts with diaryliodonium salts. replaced by a bromo-, trifluoromethyloxyl or trifluoromethyl
First, N-pyridine tosylamidate (2a) was reacted with a range of group (1n–1p), the reaction could not give the rearrangement
diaryliodonium salts with various substituents on the aromatic product. These results suggest that an electro-donating substi-
ring (1a–1k) at 130 °C (reaction 3; for results, see Scheme 4). tuent on the phenyl ring of the diaryliodonium salts is
When the substituent R1 or R2 was an electron-donating group required for the rearrangement, but an electron withdrawing
such as H or a methyl or dimethyl group, the reaction worked substituent inhibits the rearrangement.
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Fig. 1 Crystal structure of compound 3kb. The counter anion of triflate
and hydrogen atoms are omitted for clarity.
with bromo-, chloro- and trifluoromethyloxyl groups to gene-
rate the rearrangement products.
The reaction of diaryliodonium triflate (1q) and pyridinium
sulfonamidate (2a) gave the arylated product, which did not
undergo the rearrangement reaction. Over-long heating of the
arylated product gave the decomposition product 7, presum-
ably via radical reduction (reaction 4):
ð4Þ
The reaction of pyridinium sulfonamidate with meta-substi-
tuted diaryliodonium triflate produced the regio-isomer. For
example, 3-chloropyridinium sulfonamidate reacted with di-
(m-tolyl) iodonium triflate to give two isomers in a ratio of 3 : 2
(reaction 5):
Scheme 3 Isolated yields of the series of products (3).
Encouraged by these results, we attempted to investigate
the influence of the substitution of pyridinium sulfonamidate
on the rearrangement. To achieve this, a series of substituted
pyridinium sulfonamidates was reacted with diaryliodonium
salts to generate the rearrangement products (Scheme 5). Inter-
estingly, the pyridinium sulfonamidates with electron-donat-
ing groups (2b–2e) could react with electron-enriched
iodonium salts to give the rearrangement products 4db–4de,
The reaction of 2c with electron-deficient iodonium salts (1h,
1k, 1n–1p) did not give any rearrangement products.
ð5Þ
Finally, the effect of a protecting group on the amide
moiety was investigated. In a similar manner to the tosylate
group, pyridinium benzenesulfonamidate amide (2g) also
worked with ditolyliodonium triflate (1d) to give the rearrange-
ment product in good yield (reaction 6):
Halogen-substituted pyridinium sulfonamidates were more
reactive and gave rearrangement products (Scheme 6). 3-Chloro-
pyridinium sulfonamidates reacted with diaryliodonium salts
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Fig. 2 Crystal structure of 4da. Counter anions and hydrogen atoms
are omitted for clarity.
Scheme 4 Diaryliodonium triflates (1) (hexafluorophosphate for 1a) and
pyridinium sulfonamidates (2a) used in the reaction for the preparation
of products (4).
Scheme 5 Diaryliodonium triflates (1) and pyridinium N-sulfonamidates
with electron-donating groups (2) used in the reaction for the prepa-
ration of products (4).
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Fig. 3 Crystal structure of 6a. The counter anion and hydrogen atoms
are omitted for clarity.
obtained instead (reaction 7). The structure of product 6a was
confirmed by single-crystal XRD analysis (Fig. 3).12
ð7Þ
Conclusions
We have reported here a regio-selective method of synthesizing
benzene derivatives with vicinal disubstitution by the reaction
of diaryliodonium salts with pyridinium N-sulfonamidates.
The reaction proceeds via the arylation of pyridinium N-sulfo-
namidates followed by the key rearrangement of the arylated
products 3 (Fig. 4). Previously reported studies and this work
have proved that the rearrangement is generally initiated by a
homo-cleavage to give a radical pair: the tosylate aniline
Scheme 6 Diaryliodonium triflates (1) (hexafluorophosphate for 1a) and
halogen-substituted pyridinium sulfonamidates (2) used in the reactions
for the preparation of products (4).
ð6Þ
Fig. 4 Likely reaction mechanism for the synthesis of benzene deriva-
tives with vicinal disubstitution by the reaction of diaryliodonium salts
When the protecting group on the amide moiety was
changed to a benzoate group, the o-arylated product was with pyridinium N-sulfonamidates.
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General procedure for the preparation of the desired
compound 3
Cu(OTf)2 (0.05 mmol) was added to a mixture of the appropri-
ate N-tosylpyridinium imides or N-pyridine tosylamidates (or
N-pyridinium benzene sulfonated amide) (2) (0.5 mmol) and
the appropriate diaryliodonium salt (1) (0.5 mmol) in a sealed
tube. The tube was then evacuated and recharged three times
with N2. After 2 mL of dichloroethane (DCE) had been added,
the tube was sealed and the mixture was stirred at 75 °C for
12 h until the reaction was complete [confirmed using thin
layer chromatography (TLC)]. Finally, the desired compound 3
was purified using silica gel column chromatography
(dichloromethane–petroleum ether–methanol = 5 : 5 : 1) and
was obtained as a yellow solid.
Scheme 7 Influence of the substituents on the pyridinium ring and the
phenyl ring on the rearrangement reactions.
radical A13 and the pyridinium radical B.14 The recombination
of the radical pair gives the final product 4 and this process is
sensitively influenced by the substituents on the pyridinium
and phenyl rings (Scheme 6). This result shows that the nature
of the radical rearrangement depends on the electrophilic sub-
stitution on the phenyl ring (Scheme 7).15
General procedure for the preparation of desired compound 4
Cu(OTf)2 (0.05 mmol) was added to a mixture of the appropri-
ate N-pyridine tosylamidates (or N-pyridinium benzene sulfo-
nated amide) (2) (0.5 mmol) and the appropriate
diaryliodonium salt (1) (0.5 mmol) in a sealed tube. The tube
was then evacuated and recharged three times with N2. After
2 mL of DCE had been added, the tube was sealed and the
mixture was stirred at 130 °C for 48 h until completion of the
reaction (confirmed using TLC). Finally, the desired com-
pound 4 was purified using a silica gel column chromato-
graphy (dichloromethane–petroleum ether–methanol = 5 : 3 : 1)
and was obtained as a yellow solid.
Experimental section
All the reactions were carried out in a pre-dried screw-capped
tube with a Teflon-lined septum under an N2 atmosphere.
Diphenyliodonium hexafluorophosphate (Ph2IPF6) was pur-
chased from Alfa Aesar. The other diaryliodonium salt used
was diaryl iodonium triflate (Ar2IOTf) because its activity is
almost the same as that of diaryliodonium hexafluoro-
phosphate (Ar2IPF6) (only a slight decrease) and Ar2IOTf is
easier to synthesize. All the solvents were freshly distilled.
Column chromatography was carried out using a silica gel
column (particle size 10–40 μm, Ocean Chemical Factory of
Qingdao, China). 1H-NMR and 13C-NMR spectra were recorded
on a Jeol AL-300 MHz or AL-400 MHz spectrometer at ambient
temperature with deuterated chloroform (CDCl3), deuterated
1-(4-Methyl-N-phenylphenylsulfonamido)pyridin-1-ium hexa-
fluorophosphate(V) (3aa). Yellow solid (134 mg, 0.28 mmol,
1
57%). H-NMR (301 MHz, CD3OD): δ 9.47 (d, J = 5.8 Hz, 2H),
8.88 (t, J = 7.8 Hz, 1H), 8.31 (t, J = 7.2 Hz, 2H), 7.81–7.70 (m,
4H), 7.60–7.49 (m, 5H), 2.52 (s, 3H). 13C-NMR (76 MHz,
CD3OD): δ 149.69, 148.07 (2 × CH), 147.92, 137.53, 131.59,
131.41, 130.73 (2 × CH), 130.40 (2 × CH), 129.97 (2 × CH),
129.03 (2 × CH), 128.57 (2 × CH), 20.54. ESI-MS: m/z calculated
− +
for C18H17N2O2S [M − PF6
] 325.1; found 325.0. ESI-HRMS:
− +
m/z calculated for C18H17N2O2S [M − PF6
] 325.1005; found
325.1005.
methanol
(CD3OD)
or
deuterated
dimethylsulfoxide
1-(4-Methyl-N-(o-tolyl)phenylsulfonamido)pyridin-1-ium tri-
fluoromethanesulfonate (3ba). Yellow solid (188 mg,
0.39 mmol, 77%). 1H-NMR (400 MHz, CD3OD): δ 9.40 (d, J =
5.9 Hz, 2H), 8.82 (t, J = 7.8 Hz, 1H), 8.25 (d, J = 7.4 Hz, 1H),
7.76 (d, J = 7.5 Hz, 1H), 7.69 (d, J = 8.3 Hz, 2H), 7.53–7.44 (m,
3H), 7.38 (t, J = 7.0 Hz, 2H), 2.50 (s, 3H), 2.41 (s, 3H). 13C-NMR
(101 MHz, CD3OD): δ 149.40, 148.04, 147.73 (2 × CH), 140.34,
135.78, 132.34, 132.01, 131.23, 130.73 (2 × CH), 129.76 (2 ×
CH), 129.24, 129.16 (2 × CH), 127.70, 120.47 (q, J = 318.5 Hz),
20.51, 17.45. ESI-MS: m/z calculated for C19H19N2O2S [M −
TfO−]+ 339.1; found 339.0. ESI-HRMS: m/z calculated for
C19H19N2O2S [M − TfO−]+ 339.1162; found 339.1166.
(DMSO-D6) as the solvent. Chemical shifts (δ) are given in
ppm, referenced to the residual proton resonance of CDCl3
(7.26), CD3OD (3.31) and DMSO-D6 (2.50) and to the carbon
resonance of CDCl3 (77.16), CD3OD (49.00) and DMSO-D6
(39.52). Coupling constants (J) are given in Hertz (Hz). The
terms m, dq, q, t, d and s refer to multiplet, doublet quartet,
quartet, triplet, doublet and singlet peaks. Mass spectra were
obtained using a Bruker Esquire ion trap mass spectrometer
in the positive mode.
Preparation of starting materials
The diaryliodonium salts were synthesized according to pre-
1-(4-Methyl-N-(m-tolyl)phenylsulfonamido)pyridin-1-ium tri-
viously published procedures.7 The N-pyridine tosylamidates fluoromethanesulfonate (3ca). Yellow solid (149 mg,
(2a–2f, 2h), the N-pyridinium benzene sulfonated amide (2g) 0.31 mmol, 61%). 1H-NMR (400 MHz, CD3OD): δ 9.40 (d, J =
and the N-pyridinium benzoated amides (5a–5b) were all also 5.7 Hz, 2H), 8.83 (t, J = 7.8 Hz, 1H), 8.25 (dd, J = 7.6, 6.9 Hz,
synthesized according to previously published procedures.16
2H), 7.72 (d, J = 8.4 Hz, 2H), 7.50 (dd, J = 13.3, 5.3 Hz, 4H),
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7.41–7.33 (m, 2H), 2.49 (s, 3H), 2.36 (s, 3H). 13C-NMR 343.0. ESI-HRMS: m/z calculated for C18H16FN2O2S [M −
(101 MHz, CD3OD): δ 149.59, 148.01 (2 × CH), 147.82, 141.12, TfO−]+ 343.0911; found 343.0912.
137.44, 132.04, 131.64, 130.67 (2 × CH), 130.02, 129.89 (2 ×
1-(N-(4-Fluorophenyl)-4-methylphenylsulfonamido)pyridin-1-
CH), 129.01 (2 × CH, 1 × C), 125.46, 120.46 (q, J = 318.7 Hz), ium trifluoromethanesulfonate (3ha). Yellow solid (209 mg,
1
20.48, 19.82. ESI-MS: m/z calculated for C19H19N2O2S [M − 0.43 mmol, 85%). H-NMR (400 MHz, DMSO-D6): δ 9.65 (d, J =
TfO−]+ 339.1; found 339.0. ESI-HRMS: m/z calculated for 6.4 Hz, 2H), 8.89 (t, J = 7.3 Hz, 1H), 8.36 (t, J = 7.1 Hz, 2H),
C19H19N2O2S [M − TfO−]+ 339.1162; found 339.1163.
7.93–7.84 (m, 2H), 7.72 (d, J = 8.1 Hz, 2H), 7.54 (d, J = 7.9 Hz,
1-(4-Methyl-N-(p-tolyl)phenylsulfonamido)pyridin-1-ium tri- 2H), 7.41 (dd, J = 12.1, 5.1 Hz, 2H), 2.46 (s, 3H). 13C-NMR
fluoromethanesulfonate (3da). Yellow solid (220 mg, (101 MHz, DMSO-D6): δ 163.86 (d, J1 = 250.3 Hz), 150.57,
0.45 mmol, 90%). 1H-NMR (301 MHz, CD3OD): δ 9.46 (d, J = 148.64 (2 × CH), 147.64, 133.55, 132.71 (d, J3 = 9.6 Hz), 131.82,
6.5 Hz, 2H), 8.88 (t, J = 7.8 Hz, 1H), 8.30 (t, J = 6.8 Hz, 2H), 131.43 (2 × CH), 130.78 (2 × CH), 129.37 (2 × CH), 121.21 (q, J =
7.76 (d, J = 7.5 Hz, 2H), 7.61 (d, J = 8.1 Hz, 2H), 7.54 (d, J = 8.0 322.4 Hz), 117.86 (d, J2 = 23.2 Hz), 21.79. ESI-MS: m/z calcu-
Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 2.53 (s, 3H), 2.41 (s, 3H). lated for C18H16FN2O2S [M − TfO−]+ 343.1; found 343.0.
13C-NMR (76 MHz, CD3OD): δ 149.54, 147.93 (2 × CH), 147.79, ESI-HRMS: m/z calculated for C18H16FN2O2S [M − TfO−]+
142.48, 134.87, 131.65, 130.84 (2 × CH), 130.66 (2 × CH), 343.0911; found 343.0912.
129.89 (2 × CH), 129.02 (2 × CH), 128.63 (2 × CH), 120.50 (q, J =
1-(N-(2-Chlorophenyl)-4-methylphenylsulfonamido)pyridin-1-
316.5 Hz), 20.49, 19.92. ESI-MS: m/z calculated for ium trifluoromethanesulfonate (3ia). Yellow solid (181 mg,
C19H19N2O2S [M − TfO−]+ 339.1; found 339.0. ESI-HRMS: m/z 0.36 mmol, 71%). 1H-NMR (301 MHz, CD3OD): δ 9.41 (d, J =
calculated for C19H19N2O2S [M − TfO−]+ 339.1162; found 6.0 Hz, 2H), 8.84 (t, J = 7.7 Hz, 1H), 8.26 (t, J = 7.0 Hz, 1H), 8.06
339.1161.
(dd, J = 6.6, 1.8 Hz, 1H), 7.75 (d, J = 8.3 Hz, 2H), 7.61–7.48 (m,
1-(N-(2,4-Dimethylphenyl)-4-methylphenylsulfonamido)-pyri- 5H), 2.49 (s, 3H). 13C-NMR (76 MHz, CD3OD): δ 149.89, 148.25,
dine-1-ium trifluoromethanesulfonate (3ea). Yellow solid 148.16 (2 × CH), 135.57, 133.79, 133.55, 131.64, 131.43, 131.20,
(138 mg, 0.28 mmol, 55%). 1H-NMR (301 MHz, CD3OD): δ 9.03 130.80 (2 × CH), 129.82 (2 × CH), 129.09 (2 × CH), 128.90,
(d, J = 5.8 Hz, 2H), 8.71 (t, J = 7.8 Hz, 1H), 8.19 (t, J = 6.9 Hz, 120.46 (q, J = 318.5 Hz), 20.55. ESI-MS: m/z calculated for
1H), 7.47–7.38 (m, 3H), 7.27 (dd, J = 14.5, 8.2 Hz, 4H), 2.42 (s, C18H16ClN2O2S [M − TfO−]+ 359.1; found 359.0. ESI-HRMS:
6H), 1.74 (s, 3H). 13C-NMR (76 MHz, CD3OD): δ 146.75 (2 × m/z calculated for C18H16ClN2O2S [M − TfO−]+ 359.0616; found
CH), 146.61, 144.46, 139.96, 139.46, 137.19, 134.52, 129.68 (2 × 359.0616.
CH), 128.64, 127.24 (2 × CH), 126.76 (2 × CH), 125.67, 125.24,
1-(N-(3-Chlorophenyl)-4-methylphenylsulfonamido)pyridin-1-
120.44 (q, J = 318.8 Hz), 20.19, 19.55, 16.31. ESI-MS: m/z calcu- ium trifluoromethanesulfonate (3ja). Yellow solid (183 mg,
1
lated for C20H21N2O2S [M − TfO−]+ 353.13; found 353.2. 0.36 mmol, 72%). H-NMR (400 MHz, CD3OD): δ 9.40 (dd, J =
ESI-HRMS: m/z calculated for C20H21N2O2S [M − TfO−]+ 4.2, 2.5 Hz, 2H), 8.85 (t, J = 7.8 Hz, 1H), 8.27 (t, J = 7.5 Hz, 1H),
353.1318; found 353.1317.
7.81 (t, J = 2.0 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.66 (ddd, J =
1-(N-(2-Fluorophenyl)-4-methylphenylsulfonamido)pyridin-1- 7.9, 2.0, 1.1 Hz, 1H), 7.59–7.55 (m, 1H), 7.52 (d, J = 7.8 Hz, 3H),
ium trifluoromethanesulfonate (3fa). Yellow solid (199 mg, 2.49 (s, 3H). 13C-NMR (101 MHz, CD3OD): δ 149.92, 148.20,
1
0.41 mmol, 81%). H-NMR (301 MHz, DMSO-D6): δ 9.43 (d, J = 148.11 (2 × CH), 138.29, 135.49, 131.51, 131.49, 131.22, 130.84
6.0 Hz, 2H), 8.87 (t, J = 7.7 Hz, 1H), 8.32 (t, J = 7.1 Hz, 2H), 8.00 (2 × CH), 130.04 (2 × CH), 129.02 (2 × CH), 128.78, 126.87,
(dd, J = 11.2, 4.3 Hz, 1H), 7.73–7.61 (m, 3H), 7.52 (d, J = 8.2 Hz, 120.46 (q, J = 318.5 Hz), 20.53. ESI-MS: m/z calculated for
2H), 7.49–7.35 (m, 2H), 2.46 (d, J = 9.8 Hz, 3H). 13C-NMR C18H16ClN2O2S [M − TfO−]+ 359.1; found 359.0. ESI-HRMS:
(76 MHz, DMSO-D6): δ 159.56 (d, J1 = 253.8 Hz), 150.81, 148.83 m/z calculated for C18H16ClN2O2S [M − TfO−]+ 359.0616; found
(2 × CH), 147.81, 135.11 (d, J3 = 8.6 Hz), 132.43, 131.93, 131.48 359.0616.
(2 × CH), 130.91 (2 × CH), 129.20 (2 × CH), 126.50 (d, J3 = 3.1
1-(N-(4-Chlorophenyl)-4-methylphenylsulfonamido)pyridin-1-
Hz), 124.36 (d, J2 = 12.8 Hz) 121.23 (q, J = 322.1 Hz), 118.01 (d, ium trifluoromethanesulfonate (3ka). Yellow solid (214 mg,
J2 = 19.7 Hz), 21.79. ESI-MS: m/z calculated for C18H16FN2O2S 0.36 mmol, 84%). H-NMR (400 MHz, CD3OD): δ 9.40 (dd, J =
1
[M − TfO−]+ 343.1; found 343.0. ESI-HRMS: m/z calculated for 4.2, 2.5 Hz, 2H), 8.85 (t, J = 7.8 Hz, 1H), 8.27 (t, J = 7.5 Hz, 1H),
C18H16FN2O2S [M − TfO−]+ 343.0911; found 343.0912.
7.81 (t, J = 2.0 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.66 (ddd, J =
1-(N-(3-Fluorophenyl)-4-methylphenylsulfonamido)pyridin-1- 7.9, 2.0, 1.1 Hz, 1H), 7.59–7.55 (m, 1H), 7.52 (d, J = 7.8 Hz, 3H),
ium trifluoromethanesulfonate (3ga). Yellow solid (185 mg, 2.49 (s, 3H). 13C-NMR (101 MHz, CD3OD): δ 149.92, 148.20,
0.38 mmol, 75%). 1H-NMR (400 MHz, CD3OD): δ 9.40 (d, J = 148.11 (2 × CH), 138.29, 135.49, 131.51, 131.49, 131.22, 130.84
5.9 Hz, 2H), 8.86 (t, J = 7.8 Hz, 1H), 8.28 (t, J = 7.2 Hz, 2H), 7.74 (2 × CH), 130.04 (2 × CH), 129.02 (2 × CH), 128.78, 126.87,
(d, J = 8.3 Hz, 2H), 7.58–7.48 (m, 5H), 7.36–7.27 (m, 1H), 2.49 120.46 (q, J = 318.5 Hz), 20.53. ESI-MS: m/z calculated for
(s, 3H). 13C-NMR (101 MHz, CD3OD): δ 162.91 (d, J1 = 249.3 C18H16ClN2O2S [M − TfO−]+ 359.1; found 359.0. ESI-HRMS:
Hz), 149.91, 148.14 (3 × CH), 138.42 (d, J2 = 9.8 Hz), 131.79 (d, m/z calculated for C18H16ClN2O2S [M − TfO−]+ 359.0616; found
J3 = 8.8 Hz), 131.25, 130.81 (2 × CH), 130.03 (2 × CH), 129.03 359.0616.
(2 × CH), 124.26 (d, J3 = 3.3 Hz), 120.48 (q, J = 318.8 Hz),
1-(N-(2-Bromophenyl)-4-methylphenylsulfonamido)pyridin-1-
118.30 (d, J2 = 21.1 Hz), 115.84 (d, J = 24.3 Hz), 20.50. ESI-MS: ium trifluoromethanesulfonate (3la). Yellow solid (199 mg,
m/z calculated for C18H16FN2O2S [M − TfO−]+ 343.1; found 0.36 mmol, 72%). 1H-NMR (400 MHz, CD3OD): δ 9.40 (d, J =
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6.1 Hz, 2H), 8.81 (t, J = 7.7 Hz, 1H), 8.23 (t, J = 7.1 Hz, 2H), 8.04 C19H16F3N2O2S [M − TfO−]+ 393.1; found 393.0. ESI-HRMS:
(d, J = 7.7 Hz, 1H), 7.71 (t, J = 8.6 Hz, 3H), 7.56 (t, J = 7.4 Hz, m/z calculated for C19H16F3N2O2S [M − TfO−]+ 393.0879; found
1H), 7.46 (t, J = 8.3 Hz, 3H), 2.45 (s, 3H). 13C-NMR (76 MHz, 393.0882.
CD3OD): δ 149.87, 148.36, 148.05 (2 × CH), 135.25, 134.80,
2-Methyl-1-(4-methyl-N-phenylphenylsulfonamido)pyridin-1-
133.67, 131.75, 130.88, 130.82 (2 × CH), 129.75 (2 × CH), ium trifluoromethanesulfonate (3ab). Yellow solid (108 mg,
129.55, 129.22 (2 × CH), 125.87, 120.45 (q, J = 318.5 Hz), 20.58. 0.23 mmol, 45%). 1H-NMR (400 MHz, CD3OD): δ 9.19 (d, J =
ESI-MS: m/z calculated for C18H16BrN2O2S [M − TfO−]+ 403.0; 6.3 Hz, 1H), 8.75 (t, J = 7.7 Hz, 1H), 8.29 (d, J = 7.8 Hz, 1H),
found 403.0. ESI-HRMS: m/z calculated for C18H16BrN2O2S 8.16 (t, J = 6.7 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.64 (dd, J = 6.6,
[M − TfO−]+ 403.0110; found 403.0115.
3.1 Hz, 2H), 7.60–7.50 (m, 5H), 3.05 (s, 3H), 2.54 (s, 3H).
1-(N-(3-Bromophenyl)-4-methylphenylsulfonamido)pyridin-1- 13C-NMR (101 MHz, CD3OD): δ 161.02, 148.96, 148.05, 147.37,
ium trifluoromethanesulfonate (3ma). Yellow solid (193 mg, 136.86, 131.87, 131.59, 130.82 (2 × CH), 130.47, 130.35 (2 ×
0.35 mmol, 70%). 1H-NMR (400 MHz, CD3OD): δ 9.43 (d, J = CH), 128.93 (2 × CH), 127.48, 126.86 (2 × CH), 120.51 (q, J =
5.6 Hz, 2H), 8.86 (t, J = 7.8 Hz, 1H), 8.27 (t, J = 7.5 Hz, 1H), 7.95 318.4 Hz), 20.53, 19.33. ESI-MS: m/z calculated for
(t, J = 2.0 Hz, 1H), 7.77–7.67 (m, 4H), 7.53 (d, J = 8.3 Hz, 2H), C19H19N2O2S [M − TfO−]+ 339.1; found 339.0. ESI-HRMS: m/z
7.46 (t, J = 8.1 Hz, 1H), 2.51 (s, 3H). 13C-NMR (101 MHz, calculated for C19H19N2O2S [M − TfO−]+ 339.1162; found
CD3OD): δ 149.88, 148.15 (2 × CH, 1 × C), 138.38, 134.47, 339.1162.
131.67 (2 × CH), 131.35, 130.80 (2 × CH), 130.00 (2 × CH),
1-(N-(4-Chlorophenyl)-4-methylphenylsulfonamido)-2-methyl-
129.02 (2 × CH), 127.28, 123.04, 120.48 (q, J = 318.4 Hz), 20.49. pyridin-1-ium trifluoromethanesulfonate (3kb). Yellow solid
ESI-MS: m/z calculated for C18H16BrN2O2S [M − TfO−]+ 403.0; (240 mg, 0.46 mmol, 92%). 1H-NMR (301 MHz, CD3OD): δ 9.16
found 403.0. ESI-HRMS: m/z calculated for C18H16BrN2O2S (dd, J = 6.6, 1.1 Hz, 1H), 8.75 (td, J = 7.9, 1.2 Hz, 1H), 8.29 (dd,
[M − TfO−]+ 403.0110; found 403.0111.
J = 8.1, 1.5 Hz, 1H), 8.14 (td, J = 7.7, 1.6 Hz, 1H), 7.75 (d, J =
1-(N-(4-Bromophenyl)-4-methylphenylsulfonamido)pyridin-1- 8.4 Hz, 2H), 7.67–7.59 (m, 2H), 7.57 (t, J = 2.4 Hz, 2H), 7.55 (d,
ium trifluoromethanesulfonate (3na). Yellow solid (177 mg, J = 2.7 Hz, 2H), 3.03 (s, 3H), 2.54 (s, 3H). 13C-NMR (76 MHz,
1
0.32 mmol, 64%). H-NMR (301 MHz, DMSO-D6): δ 9.61 (d, J = CD3OD): δ 161.15, 149.05, 148.24, 147.26, 136.44, 135.35,
5.8 Hz, 2H), 8.90 (t, J = 7.8 Hz, 1H), 8.35 (t, J = 7.3 Hz, 1H), 131.67, 131.61, 130.87 (2 × CH), 130.35 (2 × CH), 128.97 (2 ×
7.80–7.70 (m, 6H), 7.54 (d, J = 8.3 Hz, 2H), 2.47 (s, 3H). CH), 128.54 (2 × CH), 127.49, 124.86 (q, J = 346.1 Hz), 20.48,
13C-NMR (76 MHz, DMSO-D6): δ 150.68, 148.72 (2 × CH), 19.25. ESI-MS: m/z calculated for C19H18ClN2O2S [M − TfO−]+
147.78, 136.66, 133.86 (2 × CH), 131.68, 131.47 (2 × CH), 373.0; found 372.9. ESI-HRMS: m/z calculated for
131.43 (2 × CH), 130.80 (2 × CH), 129.41 (2 × CH), 125.47, C19H18ClN2O2S [M − TfO−]+ 373.0772; found 373.0770.
121.22 (q, J = 322.2 Hz), 21.81. ESI-MS: m/z calculated for
X-ray crystal structure analysis of compound 3kb. Single
C18H16BrN2O2S [M − TfO−]+ 403.0; found 413.0. ESI-HRMS: crystals suitable for X-ray analysis were obtained by slow evap-
m/z calculated for C18H16BrN2O2S [M − TfO−]+ 403.0110; found oration of the solution of compound 3kb in CH3OH. The
403.0113.
crystal structure has been deposited at the Cambridge Crystal-
1-(4-Methyl-N-(4-(trifluoromethoxy)phenyl)phenylsulfona- lographic Data Centre and allocated the deposition number
mido)pyridin-1-ium trifluoromethanesulfonate (3oa). Yellow CCDC 1008472. Formula: C20H18ClF3N2O5S2, M = 522.95, color-
1
solid (195 mg, 0.32 mmol, 70%). H-NMR (400 MHz, CD3OD): less crystals, 0.20 × 0.14 × 0.13 mm, a = 8.6089(17), b = 8.8898
δ 9.39 (d, J = 5.7 Hz, 2H), 8.85 (t, J = 7.8 Hz, 1H), 8.27 (t, J = 7.3 (18), c = 15.632(3) Å, α = 98.35(3), β = 96.13(3), γ = 104.16(3), V =
Hz, 1H), 7.84 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.51 1135.0(4) Å3, ρcalc = 1.530 g cm−3, μ = 0.412 mm−1, Z = 2, tri-
ˉ
(d, J = 8.2 Hz, 2H), 7.42 (d, J = 8.6 Hz, 2H), 2.49 (s, 3H). clinic, space group P1, λ = 0.71073 Å, T = 173(2) K. Data com-
13C-NMR (101 MHz, CD3OD): δ 150.80, 149.86, 148.16, 148.07 pleteness = 0.987, theta (max) = 27.46, R (reflections) = 0.0884,
(2 × CH), 135.76, 131.23, 130.90 (2 × CH), 130.84 (2 × CH), wR2 (reflections) = 0.2084 (5129).
130.04 (2 × CH), 129.00, 122.38, 120.42 (q, J = 318.5 Hz), 120.31
3-Methyl-1-(4-methyl-N-(p-tolyl)phenylsulfonamido)pyridin-1-
(q, = 257.4 Hz), 20.51. ESI-MS: m/z calculated for ium trifluoromethanesulfonate (3dc). Yellow solid (221 mg,
J
1
C19H16F3N2O3S [M − TfO−]+ 409.1; found 409.0. ESI-HRMS: 0.44 mmol, 88%). H-NMR (301 MHz, CD3OD): δ 9.28 (s, 1H),
m/z calculated for C19H16F3N2O3S [M − TfO−]+ 409.0828; found 9.19 (d, J = 6.1 Hz, 1H), 8.64 (d, J = 7.9 Hz, 1H), 8.11 (dd, J =
409.0829.
7.8, 6.6 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz,
1-(4-Methyl-N-(4-(trifluoromethyl)phenyl)phenylsulfona- 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 2.59 (s,
mido)pyridin-1-ium trifluoromethanesulfonate (3pa). Yellow 3H), 2.48 (s, 3H), 2.35 (s, 3H). 13C-NMR (76 MHz, CD3OD):
solid (177 mg, 0.32 mmol, 65%). 1H-NMR (301 MHz, δ 150.04, 147.67, 147.20, 144.88, 142.41, 142.32, 134.92,
DMSO-D6): δ 9.63 (d, J = 5.9 Hz, 2H), 8.93 (t, J = 7.6 Hz, 1H), 131.79, 130.78 (2 × CH), 130.61 (2 × CH), 129.03 (2 × CH),
8.38 (t, J = 7.0 Hz, 2H), 7.94 (s, 4H), 7.80 (d, J = 8.2 Hz, 2H), 128.83, 128.66 (2 × CH), 120.52 (q, J = 318.4 Hz), 20.50, 19.93,
7.55 (d, J = 8.1 Hz, 2H), 2.47 (s, 3H). 13C-NMR (76 MHz, 17.08. ESI-MS: m/z calculated for C20H21N2O2S [M − TfO−]+
DMSO-D6): δ 150.93, 149.07 (2 × CH), 147.97, 140.94, 131.66, 353.1318; found 353.1. ESI-HRMS: m/z calculated for
131.57 (2 × CH), 131.03 (q, J = 31.7 Hz), 130.92, 129.48 (2 × C20H21N2O2S [M − TfO−]+ 353.1318; found 353.1319.
CH), 128.78 (2 × CH), 127.96 (q, J = 3.2 Hz), 124.01 (q, J = 272.7
1-(N-(4-Chlorophenyl)-4-methylphenylsulfonamido)-4-methyl-
Hz), 121.22 (q, J = 322.1 Hz), 21.83. ESI-MS: m/z calculated for pyridin-1-ium trifluoromethanesulfonate (3kd). Yellow solid
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(230 mg, 0.44 mmol, 88%). 1H-NMR (301 MHz, CD3OD): δ 8.87 443.0; found 443.0. ESI-HRMS: m/z calculated for
(d, J = 6.8 Hz, 2H), 8.06 (d, J = 6.6 Hz, 2H), 7.75 (d, J = 8.2 Hz, C19H15ClF3N2O3S [M − TfO−]+ 443.0439; found 443.0438.
2H), 7.36 (d, J = 8.9 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H), 6.83 (d, J =
3-Chloro-1-(4-methyl-N-(4-(trifluoromethyl)phenyl)-phenylsul-
8.9 Hz, 2H), 2.77 (s, 3H), 2.40 (s, 3H). 13C-NMR (76 MHz, fonamido)pyridin-1-ium
trifluoromethanesulfonate (3pf).
CD3OD): δ 161.75, 145.37 (2 × CH), 143.89, 141.22, 141.04, Yellow solid (179 mg, 0.31 mmol, 62%). 1H-NMR (400 MHz,
129.96 (2 × CH), 129.59 (2 × CH), 129.12, 128.67, 125.66 (2 × DMSO-D6): δ 10.09 (s, 1H), 9.56 (d, J = 5.9 Hz, 1H), 9.03 (d, J =
CH), 120.36 (q, J = 318.4 Hz), 117.09 (2 × CH), 21.04, 20.03. 8.2 Hz, 1H), 8.35 (t, J = 7.2 Hz, 1H), 7.90 (dd, J = 20.1, 8.5 Hz,
ESI-HRMS: m/z calculated for C19H18ClN2O2S [M − TfO−]+ 4H), 7.75 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 2.41 (s,
373.0772; found 373.0772.
3H). 13C-NMR (101 MHz, DMSO-D6) δ 150.55, 148.46, 147.93,
3-Ethoxy-1-(4-methyl-N-(p-tolyl)phenylsulfonamido)pyridin-1- 147.85, 140.60, 136.98, 131.65, 131.48, 131.24 (q, J = 32.6 Hz),
ium trifluoromethanesulfonate (3de).8 Yellow solid (226 mg, 130.98, 129.53 (4 × CH), 127.78 (q, J = 3.1 Hz), 123.99 (q, J =
0.44 mmol, 85%). 1H-NMR (400 MHz, CD3OD): δ 9.07–9.05 (m, 272.7 Hz), 121.18 (q, J = 322.2 Hz), 21.79. ESI-MS: m/z calcu-
1H), 8.94–8.90 (m, 1H), 8.38–8.32 (m, 1H), 8.09 (dd, J = 8.9, lated for C19H15ClF3N2O2S [M − TfO−]+ 427.0; found 427.0.
6.3 Hz, 1H), 7.74–7.69 (m, 2H), 7.63–7.59 (m, 2H), 7.47 (d, J = ESI-HRMS: m/z calculated for C19H15ClF3N2O2S [M − TfO−]+
8.1 Hz, 2H), 7.29 (t, J = 7.5 Hz, 2H), 4.30 (dq, J = 13.9, 7.0 Hz, 427.0489; found 427.0487.
2H), 2.46 (s, 3H), 2.32 (s, 3H), 1.44 (t, J = 7.0 Hz, 3H). 13C-NMR
3-Chloro-1-(N-(4-(methoxycarbonyl)phenyl)-4-methylphenyl-
(101 MHz, CD3OD): δ 160.6, 148.9, 143.5, 140.5, 137.1, 136.1, sulfonamido)pyridin-1-ium trifluoromethanesulfonate (3qf).
135.5, 132.8, 132.0, 131.9, 130.7, 130.5, 130.3, 130.0, 129.8, Yellow solid (210 mg, 0.37 mmol, 74%). 1H-NMR (400 MHz,
129.1, 128.2, 68.4, 21.8, 21.2, 14.4.
CD3OD): δ 9.77 (s, 1H), 9.32 (d, J = 6.1 Hz, 1H), 8.89 (d, J =
3-Chloro-1-(N-(2-fluorophenyl)-4-methylphenylsulfon-amido)- 8.3 Hz, 1H), 8.23 (t, J = 7.3 Hz, 1H), 8.02 (d, J = 8.5 Hz, 2H),
pyridin-1-ium trifluoromethanesulfonate (3ff). Yellow solid 7.72 (dd, J = 8.3, 1.2 Hz, 4H), 7.46 (d, J = 8.1 Hz, 2H), 3.83 (s,
(177 mg, 0.34 mmol, 67%). 1H-NMR (400 MHz, CD3OD): δ 9.35 3H), 2.43 (s, 3H). 13C-NMR (101 MHz, CD3OD): δ 165.49,
(s, 1H), 8.93 (d, J = 6.1 Hz, 1H), 8.59 (d, J = 8.3 Hz, 1H), 7.93 (t, 149.93, 148.31, 147.92, 146.92, 140.84, 137.51, 132.06, 131.11
J = 7.3 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.41 (d, J = 6.2 Hz, 2H), (2 × CH), 130.88 (2 × CH), 130.17, 129.13 (2 × CH), 127.60 (2 ×
7.34–7.25 (m, 1H), 7.19 (d, J = 6.0 Hz, 2H), 7.09–6.94 (m, 2H), CH), 120.37 (q, J = 318.2 Hz), 51.79, 20.52. ESI-MS: m/z calcu-
2.17 (s, 3H). 13C-NMR (101 MHz, CD3OD): δ 159.27 (d, J1
=
lated for C20H18ClN2O4S [M − TfO−]+ 417.1; found 417.1.
254.0 Hz), 149.61, 147.80, 147.27, 146.75 (d, J4 = 1.1 Hz), ESI-HRMS: m/z calculated for C20H18ClN2O4S [M − TfO−]+
137.07, 134.23 (d, J3 = 8.4 Hz), 131.34, 131.20, 130.52 (2 × CH), 417.0670; found 417.0670.
129.83, 128.56 (2 × CH), 125.50 (d, J3 = 2.6 Hz), 123.71 (d, J2 =
1-(N-(p-Tolyl)phenylsulfonamido)pyridin-1-ium
trifluoro-
12.7 Hz), 120.34 (q, J = 318.3 Hz), 116.98 (d, J2 = 20.0 Hz), methanesulfonate (3dg).8 Yellow solid (209 mg, 0.44 mmol,
20.23. ESI-MS: m/z calculated for C18H15ClFN2O2S [M − TfO−]+ 88%). H-NMR (400 MHz, CD3OD): δ 9.44 (dd, J = 5.3, 1.4 Hz,
1
377.1; found 376.9. ESI-HRMS: m/z calculated for 2H), 8.84 (td, J = 7.8, 1.2 Hz, 1H), 8.27 (t, J = 7.5 Hz, 1H),
C18H15ClFN2O2S [M − TfO−]+ 377.0521; found 377.0518.
7.90–7.83 (m, 1H), 7.73–7.65 (m, 2H), 7.58 (d, J = 8.4 Hz, 2H),
1-(N-(4-Bromophenyl)-4-methylphenylsulfonamido)-3-chloro- 7.32 (d, J = 8.4 Hz, 2H), 2.36 (s, 3H). 13C-NMR (101 MHz,
pyridin-1-ium trifluoromethanesulfonate (3nf). Yellow solid CD3OD): δ 149.64, 147.96 (2 × CH), 142.59, 135.79, 134.84,
(217 mg, 0.37 mmol, 74%). 1H-NMR (400 MHz, CD3OD): δ 9.81 134.70, 130.86 (2 × CH), 130.13 (2 × CH), 129.95 (2 × CH),
(s, 1H), 9.38 (d, J = 8.2 Hz, 1H), 8.98 (d, J = 7.3 Hz, 1H), 8.27 128.95 (2 × CH), 128.77 (2 × CH), 120.48 (q, J = 318.6 Hz),
(dd, J = 8.5, 6.4 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.69–7.62 (m, 19.93. ESI-MS: m/z calculated for C18H17N2O2S [M − TfO−]+
4H), 7.52 (d, J = 8.3 Hz, 2H), 2.50 (s, 3H). 13C-NMR (101 MHz, 325.1; found 325.1. ESI-HRMS: m/z calculated for C18H17N2O2S
CD3OD): δ 149.71, 148.23, 147.68, 146.62, 137.44, 136.12, [M − TfO−]+ 325.1005; found 325.1006.
133.48 (2 × CH), 131.09, 130.86 (2 × CH), 130.67 (2 × CH),
1-(2-(4-Methylphenylsulfonamido)phenyl)pyridin-1-ium hexa-
130.12, 129.14 (2 × CH), 125.75, 120.49 (q, J = 318.6 Hz), 20.57. fluorophosphate(V) (4aa).8 Yellow solid (106 mg, 0.23 mmol,
ESI-MS: m/z calculated for C18H15BrClN2O2S [M − TfO−]+ 45%). 1H-NMR (301 MHz, DMSO-D6): δ 8.99 (dd, J = 6.6,
437.0; found 437.1; ESI-HRMS: m/z calculated for 1.2 Hz, 2H), 8.68 (tt, J = 8.0, 1.3 Hz, 1H), 8.20 (dd, J = 7.7, 6.7
C18H15BrClN2O2S [M − TfO−]+ 436.9721; found 436.9719.
3-Chloro-1-(4-methyl-N-(4-(trifluoromethoxy)phenyl)-phenyl-
Hz, 2H), 7.51 (d, J = 8.1 Hz, 2H), 7.35 (dd, J = 7.8, 1.2 Hz, 1H),
7.25–7.11 (m, 4H), 6.71 (t, J = 6.9 Hz, 1H), 2.30 (s, 3H).
sulfonamido)pyridin-1-ium trifluoromethanesulfonate (3of). 13C-NMR (76 MHz, DMSO-D6): δ 147.22 (2 × CH), 146.14,
Yellow solid (221 mg, 0.39 mmol, 78%). 1H-NMR (400 MHz, 144.18, 143.71, 139.95, 134.81, 131.43, 129.25 (2 × CH), 127.70
CD3OD): δ 9.72 (s, 1H), 9.27 (d, J = 6.0 Hz, 1H), 8.80 (d, J = (2 × CH), 126.59 (2 × CH), 125.95, 121.33, 116.73, 21.37.
− +
8.3 Hz, 1H), 8.13 (d, J = 7.2 Hz, 1H), 7.71 (d, J = 8.8 Hz, 2H), ESI-MS: m/z calculated for C18H17N2O2S [M − PF6
] 325.1;
7.63 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.5 found 325.1. ESI-HRMS: m/z calculated for C18H17N2O2S
Hz, 2H), 2.37 (s, 3H). 13C-NMR (101 MHz, DMSO-D6): δ 150.38, [M − PF6−]+ 325.1005; found 325.1004.
150.29, 148.22, 147.70, 147.58, 136.85, 135.75, 132.36 (2 × CH),
1-(3-Methyl-2-(4-methylphenylsulfonamido)phenyl)pyridin-1-
131.71, 131.39 (2 × CH), 130.88, 129.41 (2 × CH), 123.00 (2 × ium trifluoromethanesulfonate (4ba). Yellow solid (142 mg,
CH), 121.13 (d, J = 322.6 Hz), 120.30 (q, J = 257.9 Hz), 21.74. 0.29 mmol, 58%). 1H-NMR (400 MHz, CD3OD): δ 9.04 (d, J =
ESI-MS: m/z calculated for C19H15ClF3N2O3S [M − TfO−]+ 5.8 Hz, 2H), 8.70 (t, J = 7.8 Hz, 1H), 8.17 (d, J = 6.9 Hz, 1H),
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7.58 (dd, J = 6.1, 3.2 Hz, 1H), 7.53–7.44 (m, 2H), 7.42 (d, J = 8.2 calculated for C18H16FN2O2S [M − TfO−]+ 343.0911; found
Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H), 2.39 (s, 3H), 1.78 (s, 3H). 343.0907.
13C-NMR (76 MHz, CD3OD): δ 146.83 (2 × CH), 146.77, 144.67,
1-(5-Chloro-2-(4-methylphenylsulfonamido)phenyl)pyridin-1-
141.96, 139.85, 137.07, 134.14, 129.75 (2 × CH), 129.04, 128.61, ium trifluoromethanesulfonate (4ka). Yellow solid (160 mg,
127.33 (2 × CH), 126.76 (2 × CH), 124.87, 120.44 (q, J = 318.2 0.32 mmol, 63%). 1H-NMR (301 MHz, CD3OD): δ 8.92 (d, J =
Hz), 20.21, 16.35. ESI-MS: m/z calculated for C19H19N2O2S [M − 5.8 Hz, 2H), 8.75 (t, J = 7.9 Hz, 1H), 8.21 (t, J = 6.8 Hz, 1H), 7.73
TfO−]+ 339.1; found 339.0. ESI-HRMS: m/z calculated for (d, J = 2.4 Hz, 1H), 7.55 (d, J = 8.2 Hz, 2H), 7.46 (dd, J = 8.7, 2.4
C19H19N2O2S [M − TfO−]+ 339.1162; found 339.1159.
Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.8 Hz, 1H), 2.43
1-(5-Methyl-2-(4-methylphenylsulfonamido)phenyl)pyridin-1- (s, 3H). 13C-NMR (76 MHz, CD3OD): δ 146.76, 146.49 (2 × CH),
ium trifluoromethanesulfonate (4da). Yellow solid (188 mg, 143.21, 141.00, 138.11, 131.78, 129.41 (2 × CH), 129.13, 128.68
0.39 mmol, 77%). 1H-NMR (301 MHz, CD3OD): δ 9.00 (d, J = (2 × CH), 127.53 (2 × CH), 126.58, 126.44, 125.67, 120.37 (q, J =
6.3 Hz, 2H), 8.77 (t, J = 7.8 Hz, 1H), 8.24 (t, J = 6.7 Hz, 2H), 7.58 318.2 Hz), 20.16. ESI-MS: m/z calculated for C18H16ClN2O2S
(s, 1H), 7.49 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 7.7 Hz, 3H), 6.83 (d, [M − TfO−]+ 359.1; found 359.0. ESI-HRMS: m/z calculated for
J = 8.2 Hz, 1H), 3.39 (s, 3H), 2.44 (s, 3H). 13C-NMR (76 MHz, C18H16ClN2O2S [M − TfO−]+ 359.0616; found 359.0614.
CD3OD): δ 146.74, 146.57 (2 × CH), 144.31, 139.77, 139.60,
2-Methyl-1-(5-methyl-2-(4-methylphenylsulfonamido)-phenyl)-
135.85, 132.67, 129.55 (2 × CH), 128.73, 128.65, 127.48 (2 × pyridin-1-ium trifluoromethanesulfonate (4db). Yellow solid
CH), 127.34, 127.07 (2 × CH), 120.37 (q, J = 318.3 Hz), 20.23, (196 mg, 0.39 mmol, 78%). 1H-NMR (400 MHz, CD3OD): δ 8.80
19.54. ESI-MS: m/z calculated for C19H19N2O2S [M − TfO−]+ (d, J = 6.0 Hz, 1H), 8.64 (t, J = 7.8 Hz, 1H), 8.16 (d, J = 8.0 Hz,
339.1; found 339.0. ESI-HRMS: m/z calculated for C19H19N2O2S 1H), 8.03 (t, J = 6.8 Hz, 1H), 7.56 (d, J = 8.1 Hz, 3H), 7.39 (d, J =
[M − TfO−]+ 339.1162; found 339.1162.
8.1 Hz, 3H), 6.78 (d, J = 8.2 Hz, 1H), 2.62 (s, 3H), 2.44 (dd, J =
X-ray crystal structure analysis of compound 4da. Single 13.6, 2.1 Hz, 6H). 13C-NMR (101 MHz, CD3OD): δ 157.08,
crystals suitable for X-ray analysis were obtained by slow evap- 147.57, 146.84, 144.65, 140.61, 135.72, 132.89, 129.66 (2 × CH),
oration of a solution of compound 4da in CH3OH. The crystal 129.28, 128.98, 128.43, 127.85, 127.23 (2 × CH), 126.42, 124.68,
structure has been deposited at the Cambridge Crystallo- 120.48 (q, J = 318.6 Hz), 20.25, 20.11, 19.58. ESI-MS: m/z calcu-
graphic Data Centre and allocated the deposition number: lated for C20H21N2O2S [M − TfO−]+ 353.1; found 353.1.
CCDC 1008474. Formula: C19H19F6N2O2PS, M = 484.40, color- ESI-HRMS: m/z calculated for C20H21N2O2S [M − TfO−]+
less crystals, 0.48 × 0.43 × 0.26 mm, a = 15.338(3), b = 10.040(2), 353.1318; found 353.1315.
c = 14.189(3) Å, α = 90, β = 94.34(3), γ = 90, V = 2178.7(8) Å3,
3-Methyl-1-(5-methyl-2-(4-methylphenylsulfonamido)-phenyl)-
ρcalc = 1.477 g cm−3, μ = 0.291 mm−1, Z = 4, monoclinic, space pyridin-1-ium trifluoromethanesulfonate (4dc). Yellow solid
group P2(1)c, λ = 0.71073 Å, T = 173(2) K. Data completeness = (191 mg, 0.38 mmol, 76%). 1H-NMR (301 MHz, CD3OD): δ 8.82
0.997, theta (max) = 27.48, R (reflections) = 0.0811, wR2 (reflec- (s, 1H), 8.74 (d, J = 3.5 Hz, 1H), 8.53 (d, J = 7.9 Hz, 1H), 8.04
tions) = 0.2007 (4971).
(dd, J = 7.1, 4.3 Hz, 1H), 7.52 (s, 1H), 7.44 (d, J = 7.6 Hz, 2H),
1-(3,5-Dimethyl-2-(4-methylphenylsulfonamido)-phenyl)- 7.29 (d, J = 7.1 Hz, 3H), 6.78 (s, 1H), 2.61 (s, 3H), 2.41 (s, 6H).
pyridin-1-ium trifluoromethanesulfonate (4ea). Yellow solid 13C-NMR (76 MHz, CD3OD): δ 147.03 (2 × CH), 146.19, 144.01,
(121 mg, 0.24 mmol, 48%). 1H-NMR (400 MHz, CD3OD): δ 9.06 143.78, 139.57, 139.19, 138.86, 136.65, 132.40, 129.41 (2 × CH),
(d, J = 5.9 Hz, 2H), 8.75 (t, J = 7.8 Hz, 1H), 8.22 (t, J = 7.2 Hz, 128.45, 127.02 (2 × CH), 126.66 (2 × CH), 120.49 (q, J = 318.7
2H), 7.53–7.41 (m, 3H), 7.34 (d, J = 8.3 Hz, 3H), 2.45 (s, 6H), Hz), 20.16, 19.39, 17.18. ESI-MS: m/z calculated for
1.75 (s, 3H). 13C-NMR (101 MHz, CD3OD): δ 146.76 (2 × CH), C20H21N2O2S [M − TfO−]+ 353.13; found 353.1. ESI-HRMS: m/z
146.64, 144.55, 141.69, 140.06, 139.41, 137.11, 134.58, 129.72 calculated for C20H21N2O2S [M − TfO−]+ 353.1318; found
(2 × CH), 127.26 (2 × CH), 126.78 (2 × CH), 125.80, 125.30, 353.1319.
120.48 (q, J = 318.7 Hz), 20.20, 19.58, 16.28. ESI-MS: m/z calcu-
4-Methyl-1-(5-methyl-2-(4-methylphenylsulfonamido)-phenyl)-
lated for C20H21N2O2S [M − TfO−]+ 353.1; found 353.1. pyridin-1-ium trifluoromethanesulfonate (4dd). Yellow solid
ESI-HRMS: m/z calculated for C20H21N2O2S [M − TfO−]+ (201 mg, 0.4 mmol, 80%). H-NMR (400 MHz, CD3OD): δ 8.81
1
353.1312; found 353.1312.
(d, J = 6.8 Hz, 2H), 8.04 (d, J = 6.4 Hz, 2H), 7.55 (d, J = 1.2 Hz,
1-(5-Fluoro-2-(4-methylphenylsulfonamido)phenyl)pyridin-1- 1H), 7.49 (d, J = 8.3 Hz, 2H), 7.33 (dd, J = 6.0, 5.4 Hz, 3H), 6.78
ium trifluoromethanesulfonate (4ha). Yellow solid (182 mg, (d, J = 8.2 Hz, 1H), 2.79 (s, 3H), 2.44 (s, 6H). 13C-NMR
0.37 mmol, 74%). 1H-NMR (301 MHz, CD3OD): δ 9.03 (d, J = (101 MHz, CD3OD): δ 145.40 (2 × CH), 144.40, 140.00, 139.72,
5.7 Hz, 2H), 8.75 (t, J = 7.9 Hz, 1H), 8.21 (dd, J = 7.5, 6.8 Hz, 135.78, 132.48, 129.51 (3 × CH), 128.84, 128.40, 128.36, 127.87,
2H), 7.67 (dd, J = 8.1, 2.9 Hz, 1H), 7.44 (d, J = 8.3 Hz, 2H), 127.43, 127.14 (2 × CH), 120.49 (q, J = 318.5 Hz), 20.21, 20.06,
7.34–7.23 (m, 3H), 6.86 (dd, J = 8.9, 5.2 Hz, 1H), 2.35 (d, J = 19.53. ESI-MS: m/z calculated for C20H21N2O2S [M − TfO−]+
17.5 Hz, 3H). 13C-NMR (76 MHz, CD3OD): δ 162.50 (d, J1
251.1 Hz), 148.67, 147.98 (2 × CH), 145.95, 142.16 (d, J3 = 10.6 [M − TfO−]+ 353.1318; found 353.1319.
=
353.1; found 353.1. ESI-HRMS: m/z calculated for C20H21N2O2S
Hz), 136.53, 132.33, 132.21, 130.91 (2 × CH), 128.85 (2 × CH),
3-Ethoxy-1-(5-methyl-2-(4-methylphenylsulfonamido)-phenyl)-
128.45 (2 × CH), 121.69 (q, J = 318.3 Hz), 120.39 (d, J2 = 22.3 pyridin-1-ium hexafluorophosphate(V) (4de).8 Yellow solid
Hz), 116.37 (d, J2 = 27.6 Hz), 21.47. ESI-MS: m/z calculated for (193 mg, 0.37 mmol, 73%). 1H-NMR (301 MHz, CD3OD): δ 8.68
C18H16FN2O2S [M − TfO−]+ 343.1; found 343.1. ESI-HRMS: m/z (s, 1H), 8.50 (d, J = 5.8 Hz, 1H), 8.27 (dt, J = 16.8, 8.4 Hz, 1H),
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8.07 (dd, J = 8.8, 5.8 Hz, 1H), 7.59–7.44 (m, 3H), 7.33 (d, J = 8.0 Hz), 147.04, 146.36, 145.60, 144.62, 136.03, 135.21, 130.10 (d,
Hz, 3H), 6.89 (d, J = 8.1 Hz, 1H), 4.36 (q, J = 7.0 Hz, 2H), 2.41 J3 = 9.2 Hz), 129.54, 129.40 (2 × CH, 1 × C), 128.07, 126.97 (2 ×
(d, J = 16.8 Hz, 6H), 1.54 (t, J = 7.0 Hz, 3H). 13C-NMR (76 MHz, CH), 122.84 (d, J4 = 2.3 Hz), 120.43 (q, J = 318.2 Hz), 119.62 (d,
CD3OD): δ 157.79, 143.89, 139.53, 138.71, 138.59, 136.84, J2
=
21.0 Hz), 20.19. ESI-MS: m/z calculated for
134.40, 132.49, 131.88, 129.75, 129.46 (2 × CH), 128.24, 127.66, C18H15ClFN2O2S [M − TfO−]+ 377.1; found 377.0. ESI-HRMS:
127.13, 126.93 (2 × CH), 66.37, 20.19, 19.45, 13.32. ESI-MS: m/z m/z calculated for C18H15ClFN2O2S [M − TfO−]+ 377.0521;
− +
calculated for C21H23N2O3S [M − PF6
] 383.1; found 383.1. found 377.0523.
− +
ESI-HRMS: m/z calculated for C21H23N2O3S [M − PF6
]
3-Chloro-1-(5-fluoro-2-(4-methylphenylsulfonamido)-phenyl)-
383.1424; found 383.1420.
pyridin-1-ium trifluoromethanesulfonate (4hf). Yellow solid
3-Fluoro-1-(2-(4-methylphenylsulfonamido)phenyl)pyridin-1- (197 mg, 0.38 mmol, 75%). 1H-NMR (301 MHz, CD3OD): δ 9.53
ium trifluoromethanesulfonate (4ah). Yellow solid (194 mg, (s, 1H), 9.15 (d, J = 5.3 Hz, 1H), 8.92 (d, J = 8.4 Hz, 1H), 8.31
0.4 mmol, 79%). 1H-NMR (301 MHz, CD3OD): δ 9.04 (d, J = (dd, J = 7.9, 5.7 Hz, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.52 (d, J = 8.0
6.1 Hz, 1H), 8.76 (dd, J = 16.7, 8.5 Hz, 1H), 8.35 (dt, J = 8.9, 5.7 Hz, 2H), 7.40 (t, J = 12.1 Hz, 3H), 6.93 (dd, J = 8.0, 4.9 Hz, 1H),
Hz, 1H), 7.81 (dd, J = 8.8, 3.8 Hz, 1H), 7.67–7.42 (m, 5H), 7.37 2.47 (s, 3H). 13C-NMR (76 MHz, CD3OD): δ 161.35 (d, J1 = 251.6
(t, J = 8.6 Hz, 2H), 7.04–6.94 (m, 1H), 2.46 (s, 3H). 13C-NMR Hz), 147.18, 146.35, 145.57, 144.89, 140.35 (d, J3 = 13.7 Hz),
(76 MHz, CD3OD): δ 160.34 (d, J1 = 255.4 Hz), 144.62, 144.06 135.26, 135.14, 134.85, 131.17 (d, J3 = 8.8 Hz), 129.67 (2 × CH),
(d, J4 = 3.4 Hz), 139.40, 135.37, 134.35 (d, J2 = 18.6 Hz), 132.58, 128.16, 127.25 (2 × CH), 120.44 (q, J = 318.6 Hz), 119.48 (d, J2 =
131.11, 129.81, 129.58 (2 × CH), 128.93 (d, J2 = 8.1 Hz), 128.77 22.4 Hz), 115.16 (d, J2 = 27.7 Hz), 20.25. ESI-MS: m/z calculated
(d, J3 = 7.4 Hz), 127.77, 127.16 (2 × CH), 127.08, 120.44 (q, J = for C18H15ClFN2O2S [M
−
TfO−]+ 377.1; found 377.0.
318.5 Hz), 20.20. ESI-MS: m/z calculated for C18H16FN2O2S ESI-HRMS: m/z calculated for C18H15ClFN2O2S [M − TfO−]+
[M − TfO−]+ 343.1; found 343.0. ESI-HRMS: m/z calculated for 377.0521; found 377.0514.
C18H16FN2O2S [M − TfO−]+ 343.0911; found 343.0911.
3-Fluoro-1-(5-fluoro-2-(4-methylphenylsulfonamido)-phenyl)-
3-Fluoro-1-(5-fluoro-2-(4-methylphenylsulfonamido)-phenyl)- pyridin-1-ium trifluoromethanesulfonate (4kf). Yellow solid
pyridin-1-ium trifluoromethanesulfonate (4hh). Yellow solid (147 mg, 0.38 mmol, 75%). 1H-NMR (301 MHz, CD3OD): δ 9.23
1
(217 mg, 0.4 mmol, 85%). H-NMR (600 MHz, CD3OD): δ 9.54 (s, 1H), 8.91 (d, J = 5.8 Hz, 1H), 8.77 (d, J = 8.4 Hz, 1H), 8.16
(s, 1H), 9.13 (d, J = 5.6 Hz, 1H), 8.82 (t, J = 7.9 Hz, 1H), 8.42 (dt, (dd, J = 8.2, 6.2 Hz, 1H), 7.69 (d, J = 1.9 Hz, 1H), 7.51 (d, J = 8.0
J = 8.9, 5.4 Hz, 1H), 7.84 (dd, J = 7.6, 2.0 Hz, 1H), 7.56 (d, J = Hz, 2H), 7.41 (dd, J = 8.6, 1.9 Hz, 1H), 7.26 (d, J = 7.9 Hz, 2H),
8.0 Hz, 2H), 7.43 (t, J = 8.2 Hz, 3H), 6.97 (dd, J = 8.6, 5.0 Hz, 7.12 (d, J = 8.6 Hz, 1H), 2.35 (s, 3H). 13C-NMR (76 MHz,
1H), 2.50 (s, 3H). 13C-NMR (151 MHz, CD3OD): δ 162.66 (d, J1 = CD3OD): δ 147.63, 147.37, 146.71, 144.24, 139.89, 138.69,
251.8 Hz), 161.64 (d, J1 = 256.2 Hz), 146.21, 145.43 (d, J4 = 2.3 137.44, 136.34, 133.30, 130.62 (2 × CH), 129.55, 129.28, 128.21,
Hz), 141.68 (d, J3 = 9.0 Hz), 138.47 (d, J2 = 38.6 Hz), 136.24, 127.79 (2 × CH), 127.51, 121.75 (q, J = 319.2 Hz), 21.43. ESI-MS:
136.14 (d, J3 = 3.0 Hz), 132.57 (d, J2 = 8.4 Hz), 130.96 (2 × CH), m/z calculated for C18H15Cl2N2O2S [M − TfO−]+ 393.0; found
130.35 (d, J3 = 7.4 Hz), 128.53 (2 × CH), 128.25 (d, J4 = 2.0 Hz), 393.1. ESI-HRMS: m/z calculated for C18H15Cl2N2O2S [M −
121.70 (q, J = 318.2 Hz), 120.81 (d, J2 = 22.2 Hz), 116.45 (d, J2 = TfO−]+ 393.0226; found 393.0224.
28.0 Hz), 21.47. ESI-MS: m/z calculated for C18H15F2N2O2S
[M − TfO−]+ 361.1; found 361.0. ESI-HRMS: m/z calculated for pyridin-1-ium trifluoromethanesulfonate (4nf). Yellow solid
C18H15F2N2O2S [M − TfO−]+ 361.0817; found 361.0807. (199 mg, 0.34 mmol, 68%). 1H-NMR (400 MHz, DMSO-D6):
1-(5-Bromo-2-(4-methylphenylsulfonamido)phenyl)-3-chloro-
3-Chloro-1-(2-(4-methylphenylsulfonamido)phenyl)pyridin-1- δ 9.49 (s, 1H), 9.06 (d, J = 5.1 Hz, 1H), 8.91 (d, J = 8.2 Hz, 1H),
ium trifluoromethanesulfonate (4af).8 Yellow solid (193 mg, 8.27 (t, J = 6.3 Hz, 1H), 7.89 (s, 1H), 7.52 (t, J = 8.7 Hz, 3H),
1
0.38 mmol, 76%). H-NMR (301 MHz, CD3OD): δ 9.41 (s, 1H), 7.26 (d, J = 7.1 Hz, 2H), 7.12 (d, J = 8.7 Hz, 1H), 2.33 (s, 3H).
9.07 (d, J = 6.0 Hz, 1H), 8.86 (d, J = 8.3 Hz, 1H), 8.27 (d, J = 7.1 13C-NMR (101 MHz, DMSO-D6): δ 146.67, 146.32, 146.02,
Hz, 1H), 7.9–7.7 (m, 1H), 7.53 (d, J = 7.4 Hz, 4H), 7.36 (d, J = 145.98, 142.29, 139.90, 136.33, 134.97, 134.29, 134.16, 129.84
6.9 Hz, 2H), 7.05 (d, J = 25.2 Hz, 1H), 2.40 (s, 3H). 13C-NMR (2 × CH), 129.48, 128.54, 126.77 (2 × CH), 125.57, 120.99 (q, J =
(76 MHz, CD3OD): δ 147.97, 147.53, 146.81, 145.98, 140.73, 321.7 Hz), 21.39. ESI-MS: m/z calculated for C18H15BrClN2O2S
136.46, 136.34, 133.82, 132.08, 130.84 (2 × CH), 130.26, 129.81, [M − TfO−]+ 437.0; found 437.2. ESI-HRMS: m/z calculated for
129.38, 128.44 (2 × CH), 126.90, 121.72 (q, J = 318.5 Hz), 21.49. C18H15BrClN2O2S [M − TfO−]+ 436.9721; found 436.9722.
ESI-MS: m/z calculated for C18H16ClN2O2S [M − TfO−]+ 359.1;
found 359.1. ESI-HRMS: m/z calculated for C18H16ClN2O2S methoxy)phenyl)pyridin-1-ium
[M − TfO−]+ 359.0616; found 359.0613. (4of). Yellow solid (193 mg, 0.33 mmol, 65%). 1H-NMR
3-Chloro-1-(2-(4-methylphenylsulfonamido)-5-(trifluoro-
trifluoromethanesulfonate
3-Chloro-1-(3-fluoro-2-(4-methylphenylsulfonamido)-phenyl)- (400 MHz, CD3OD): δ 9.46 (s, 1H), 9.08 (d, J = 5.3 Hz, 1H), 8.86
pyridin-1-ium trifluoromethanesulfonate (4ff). Yellow solid (d, J = 8.2 Hz, 1H), 8.24 (t, J = 6.2 Hz, 1H), 7.88 (s, 1H),
(110 mg, 0.21 mmol, 42%). 1H-NMR (400 MHz, CD3OD): δ 9.58 7.58–7.46 (s, 3H), 7.34 (d, J = 6.8 Hz, 2H), 7.06 (d, J = 7.0 Hz,
(s, 1H), 9.18 (d, J = 6.0 Hz, 1H), 8.92–8.86 (m, 1H), 8.28 (dd, J = 1H), 2.43 (s, 3H). 13C-NMR (101 MHz, DMSO-D6): δ 147.37,
8.5, 6.1 Hz, 1H), 7.66 (ddd, J = 13.2, 9.6, 6.3 Hz, 2H), 7.51 (d, 146.96, 146.26, 145.09, 144.06, 137.45, 136.85, 134.43, 130.23
J = 8.3 Hz, 2H), 7.47–7.40 (m, 1H), 7.30 (d, J = 8.2 Hz, 2H), 2.42 (2 × CH), 128.84, 127.87, 127.27 (2 × CH), 126.31 (q, J =
(s, 3H). 13C-NMR (151 MHz, CD3OD): δ 158.63 (d, J1 = 254.9 63.0 Hz), 125.39, 122.76, 121.15 (q, J = 322.2 Hz), 120.40
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(q,
J
=
258.0 Hz), 21.51. ESI-MS: m/z calculated for
(Z)-1-((Phenoxy(phenyl)methylene)amino)pyridin-1-ium
C19H15ClF3N2O3S [M − TfO−]+ 443.0; found 443.1. ESI-HRMS: hexafluorophosphate(V) (6a). Cu(OTf)2 (18.1 mg, 0.05 mmol)
m/z calculated for C19H15ClF3N2O3S [M − TfO−]+ 443.0439; was added to a mixture of diphenyliodonium hexafluoro-
found 443.0436.
phosphate(V) (1a) (213 mg, 0.5 mmol) and benzoyl(pyridin-
Synthesis of methyl 4-(4-methylphenylsulfonamido)benzoate 1-ium-1-yl)amide (5a) (99.1 mg, 0.5 mmol) in a sealed tube.
(7). Cu(OTf)2 (18.1 mg, 0.05 mmol) was added to a mixture of The tube was then evacuated and recharged three times with
mesityl(4-(methoxycarbonyl)phenyl)iodonium trifluorometha- N2. After 2 mL of DCE had been added, the tube was sealed
nesulfonate 1q (265.2 mg, 0.5 mmol) and (3-chloropyridin-1- and the mixture was stirred at 130 °C for 48 h until the reac-
ium-1-yl)(tosyl)amide 2f (141.4 mg, 0.5 mmol) in a sealed tion was complete (confirmed using TLC). Finally, the desired
tube. The tube was evacuated, recharged three times with N2 compound 6a was purified using silica gel column chromato-
and then 2 mL of DCE were added. The tube was then sealed graphy (dichloromethane–petroleum ether–methanol = 5 : 3 : 1)
and the mixture was stirred at 130 °C for 48 h until the reac- and was obtained as a yellow solid (137 mg, 0.33 mmol, 65%).
tion was complete (confirmed using TLC). Finally, the desired 1H-NMR (301 MHz, DMSO-D6): δ 9.24 (d, J = 5.9 Hz, 2H), 8.52
compound 7 was purified using silica gel column chromato- (t, J = 8.3 Hz, 1H), 8.19 (t, J = 7.1 Hz, 2H), 7.77–7.69 (m, 2H),
graphy with petroleum ether–ethyl acetate (10 : 1) and was 7.54 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.5 Hz, 2H), 7.26–7.17 (m,
obtained as a yellow solid (93 mg, 0.3 mmol, 61%). 1H-NMR 2H), 7.09 (dd, J = 17.5, 7.4 Hz, 3H). 13C-NMR (76 MHz,
(400 MHz, CDCl3): δ 7.84 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.3 Hz, DMSO-D6): δ 166.95, 153.26, 144.50, 141.60, 141.31, 133.32,
2H), 7.26 (s, 1H), 7.17 (d, J = 8.2 Hz, 2H), 7.07 (d, J = 8.7 Hz, 130.11 (4 × CH), 128.88 (2 × CH), 128.67 (2 × CH), 126.76,
2H), 3.80 (s, 3H), 2.31 (s, 3H). 13C-NMR (101 MHz, CDCl3): δ 126.16, 119.86 (2 × CH). ESI-MS: m/z calculated for C18H15N2O
166.50, 144.52, 141.07, 135.79, 131.18 (2 × CH), 129.96 (2 × [M − PF6−]+ 275.1; found 275.2. ESI-HRMS: m/z calculated for
CH), 127.35 (2 × CH), 126.22, 119.06 (2 × CH), 52.22, 21.67. C18H15N2O [M − PF6−]+ 275.1179; found 275.1178.
ESI-MS: m/z calculated for C15H16NO4S [M + H]+ 306.1; found
306.6. ESI-HRMS: m/z calculated for C15H16NO4S [M + H]+ tals suitable for X-ray analysis were obtained by slow evapor-
306.0800; found 306.0801. ation of a solution of compound 6a in CH3OH. The crystal
X-ray crystal structure analysis of compound 6a. Single crys-
3-Chloro-1-(4-methyl-2-(4-methylphenylsulfonamido)-phenyl)- structure was deposited at the Cambridge Crystallographic
pyridin-1-ium trifluoromethanesulfonate (4cf-1), 3-chloro-1- Data Centre and allocated the deposition number: CCDC
(2-methyl-6-(4-methylphenylsul-fonamido)phenyl)pyridin-1-ium 1008473. Formula: C18H15F6N2OP,
M = 420.29, colorless
trifluoromethanesulfonate (4cf-2). Yellow solid [178 mg, crystal, 0.28 × 0.25 × 0.19 mm, a = 13.927(3), b = 10.771(2), c =
1
0.34 mmol, 68% (3 : 2)]. H-NMR (400 MHz, CD3OD): δ 9.38 (s, 24.361(5) Å, α = 90, β = 93.49(3), γ = 90, V = 3647.6(13) Å3, ρcalc
2H), 9.02 (d, J = 6.0 Hz, 1H), 8.97 (d, J = 6.1 Hz, 1H), 8.89 (dd, = 1.531 g cm−3, μ = 0.221 mm−1, Z = 8, monoclinic, space
J = 8.7, 0.9 Hz, 1H), 8.81 (dd, J = 8.7, 0.8 Hz, 1H), 8.27 (dd, J = group C2/c, λ = 0.71073 Å, T = 173(2) K. Data completeness =
8.5, 6.1 Hz, 1H), 8.22 (dd, J = 8.5, 6.2 Hz, 1H), 7.63 (d, J = 0.997, theta (max) = 27.47, R (reflections) = 0.0567, wR2 (reflec-
8.2 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.46 (t, J = 6.9 Hz, 2H), tions) = 0.1107 (4173).
7.44–7.37 (m, 2H), 7.37–7.31 (m, 4H), 6.75 (dd, J = 7.5, 1.3 Hz,
Synthesis of (Z)-3-methyl-1-((phenoxy(phenyl)methylene)-
1H), 6.69 (s, 1H), 2.42 (s, 5H), 2.26 (s, 3H), 2.18 (s, 2H). amino)-pyridin-1-ium hexafluorophosphate(V) (6b). Cu(OTf)2
13C-NMR (101 MHz, CD3OD): δ 147.19, 146.91, 146.40, 146.23 (18.1 mg, 0.05 mmol) was added to a mixture of diphenyliodo-
(1 × CH, 1 × C), 145.59, 144.52, 144.48, 143.73, 139.00, 136.94, nium hexafluorophosphate(V) (1a) (213 mg, 0.5 mmol) and
135.75, 135.50, 135.44, 135.10, 134.83, 132.10, 131.89, 130.92, (2-methylpyridin-1-ium-1-yl)(tosyl)amide (5b) (131.2 mg,
130.42, 129.58 (2 × CH), 129.50 (2 × CH), 129.07, 129.00, 0.5 mmol) in a sealed tube. The tube was evacuated and
128.39, 128.05, 127.21 (2 × CH), 127.15 (2 × CH), 126.66, recharged three times with N2. After 2 mL of DCE had been
126.28, 125.20, 122.03, 118.86, 115.69, 20.24, 20.23, 19.77, added, the tube was sealed and the mixture was stirred at
16.28. ESI-MS: m/z calculated for C19H18ClN2O2S [M − TfO−]+ 130 °C for 48 h until the reaction was complete (confirmed
373.1; found 373.1. ESI-HRMS: m/z calculated for using TLC). Finally, the desired compound 6b was purified by
C19H18ClN2O2S [M − TfO−]+ 373.0772; found 373.0774.
silica gel column chromatography (dichloromethane–pet-
1-(5-Methyl-2-(phenylsulfonamido)phenyl)pyridin-1-ium tri- roleum ether–methanol = 5 : 3 : 1) and was obtained as a yellow
fluoromethanesulfonate (4dg).8 Yellow solid (178 mg, solid (145 mg, 0.34 mmol, 67%). 1H-NMR (301 MHz,
0.38 mmol, 75%). 1H-NMR (400 MHz, CD3OD): δ 9.06 (d, J = DMSO-D6): δ 9.23 (s, 1H), 9.17 (d, J = 6.1 Hz, 1H), 8.44 (d, J =
5.5 Hz, 2H), 8.77 (t, J = 7.9 Hz, 1H), 8.24 (t, J = 6.8 Hz, 1H), 7.65 8.0 Hz, 1H), 8.17 (t, J = 7.1 Hz, 1H), 7.85–7.75 (m, 2H), 7.62
(t, J = 7.3 Hz, 1H), 7.63–7.56 (m, 3H), 7.52 (t, J = 7.7 Hz, 2H), (dd, J = 10.5, 4.3 Hz, 1H), 7.52 (dd, J = 8.2, 7.0 Hz, 2H), 7.30
7.32 (d, J = 8.2 Hz, 1H), 6.70 (d, J = 8.2 Hz, 1H), 2.43 (s, 3H). (dd, J = 11.2, 4.5 Hz, 2H), 7.24–7.10 (m, 3H), 2.53 (s, 3H).
13C-NMR (101 MHz, CD3OD): δ: 146.92, 146.70 (2 × CH), 13C-NMR (76 MHz, DMSO-D6): δ 167.34, 153.75, 145.31,
140.60, 140.15, 138.14, 133.34, 132.72, 129.06 (2 × CH), 128.90, 141.19, 140.23, 139.12, 133.84, 130.62 (2 × CH), 130.52 (2 ×
127.63, 127.57, 127.51 (2 × CH), 127.17 (2 × CH), 120.45 (q, J = CH), 129.44 (2 × CH), 128.33, 127.35, 126.66, 120.40 (2 × CH),
318.5 Hz), 19.56. ESI-MS: m/z calculated for C18H17N2O2S [M − 18.47. ESI-MS: m/z calculated for C19H17N2O [M − PF6−]+ 289.1;
TfO−]+ 325.1; found 325.2. ESI-HRMS: m/z calculated for found 289.1. ESI-HRMS: m/z calculated for C19H17N2O [M −
C18H17N2O2S [M − TfO−]+ 325.1005; found 325.1004.
PF6−]+ 289.1334; found 289.1333.
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Acknowledgements
This work was supported by National Natural Science Foun-
dation of China (21102080, 21372138) and Tsinghua University
Initiative Scientific Research Program (2011Z02150).
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