N,O-ditosylethanolamine as effective reagent for the synthesis of heterocyclic tertiary amine salts

Article abstract of DOI:10.1080/10426507.2015.1067207

During the synthesis of N-tosylaziridine, two unexpected products were isolated: 1-(2-(p-tolylsulfonamido)ethyl)pyridinium p-tolylsulfonate (3) and N,N,O-tri-(p-tolylsulfonyl)ethanolamine (3a). The structures of 3 and 3a were investigated in solid state b

Full text of DOI:10.1080/10426507.2015.1067207

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
N,O-Ditosylethanolamine as Effective Reagent for
the Synthesis of Heterocyclic Tertiary Amine Salts
Valeriy S. Cherepakhin, Kirill V. Zaitsev, Andrei V. Churakov, Yuri F.
Oprunenko, Galina S. Zaitseva & Sergey S. Karlov
To cite this article: Valeriy S. Cherepakhin, Kirill V. Zaitsev, Andrei V. Churakov, Yuri F.
Oprunenko, Galina S. Zaitseva & Sergey S. Karlov (2015): N,O-Ditosylethanolamine as Effective
Reagent for the Synthesis of Heterocyclic Tertiary Amine Salts, Phosphorus, Sulfur, and Silicon
and the Related Elements, DOI: 10.1080/10426507.2015.1067207
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1067207
Accepted online: 06 Oct 2015.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=gpss20
Download by: [Monash University Library]
Date: 09 October 2015, At: 22:34

ACCEPTED MANUSCRIPT
N,O-Ditosylethanolamine as Effective Reagent for the Synthesis of Heterocyclic Tertiary
Amine Salts
1
1, *
2
1
Valeriy S. Cherepakhin, Kirill V. Zaitsev, Andrei V. Churakov, Yuri F. Oprunenko, Galina
1
1
S. Zaitseva and Sergey S. Karlov
1
Department of Chemistry, Moscow State University, Leninskye Gory 1, Moscow 119991,
Russia
2
Russian Acad. Sci., N.S. Kurnakov General and Inorganic Chem. Inst., Leninskii pr., 31,
Moscow, Russia

Correspondence to: Kirill V. Zaitsev; e-mail: zaitsev@org.chem.msu.ru; phone: +8 495 939
887; fax: +8 495 932 8846.
3
Short name: N,O-Ditosylethanolamines
Absract
During the synthesis of N-tosylaziridine, two unexpected products were isolated: 1-(2-(p-
tolylsulfonamido)ethyl)pyridinium
p-tolylsulfonate
(3)
and
N,N,O-tri-(p-
tolylsulfonyl)ethanolamine (3a). The structures of 3 and 3a were investigated in solid state by X-
ray analysis. A new family of related salts was obtained using an efficient and facile one-pot
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
synthesis consisting in the interaction between various nitrogen heterocycles and N,O-
ditosylethanolamine.
Keywords
Sulfonamide; ethanolamines; synthesis; X-ray diffraction
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
INTRODUCTION
N-Tosylaziridine (2) is the most frequently used compound with the aziridine fragment;
1
futhermore this compound find wide application in organic synthesis, e.g. for obtaining 2-
2
3
aminoalkylphosphinic and phosphonic acids, and macrocyclic ionophores. Opening the
aziridine ring by nucleophiles is used in organic synthesis for the formation of –CH –CH –NR
The usual laboratory way to the formation of 2 includes two step
2
2
2
1
b,1c,1d
fragment in molecules.
4
synthesis (Scheme 1). The first stage is the tosylation of monoethanolamine using an excess of
tosylchloride in the presence of
a
base (usually, pyridine), resulting in 2-
(
tosylamino)ethyltosylate, 1. The treatment of 1 with strong base (for example, with KOH) leads
to N-tosylaziridine 2 in a good yield due to intramolecular nucleophilic substitution.
It should be noted that the prolongation of the reaction time in both steps (Scheme 1) leads
to decreasing the yields for both 1 and 2. Moreover, other products are detected in the reaction
mixture. In this article we describe the preparation of two unusual products, 3 and 3a, during the
synthesis of N-tosylaziridine (Scheme 2). The structures of these compounds were established
using X-ray diffraction analysis. The synthesis of a series of related sulfonamide salts 4-7 based
on various heterocycles (2,6-dimethylpyridine, quinoline, acridine, and imidazole) is also
described. We believe that this approach would find broad application because of the
sulfonamide product’s value. Sulfonamide derivatives find wide application in organic synthesis
5
6
7
as catalysts, in organometallic chemistry as ligands, anion recognition systems and may be
7
d, 8
regarded as components of many biologically active compounds,
such as silaxsentan
9
(
diastolic heart failure (DHF) ), naratriptan (treatment of migraine headaches), sulphapyridine
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
0
11
(
(
treatment of ocular cicatricial pemphigoid), amprenavir (HIV protease inhibitor), sulfameter
antibiotic). At the same time the sulfur containing heterocyclic salts which are acting as ionic
1
2
liquids may be used as catalysts in organic synthesis. Therefore, the synthesis of the target
compounds is the actual subject of organic chemistry and related scientific fields.
RESULTS AND DISCUSSION
In the course of this work it was established that the prolonged storage (up to 1 week at
room temperature) of the reaction mixture from the synthesis of 1 results in 3 as a main product;
so pyridine may act as a nucleophile for tosylates (Scheme 2). Furthermore, the storage of the
reaction mixture for N-tosylaziridine synthesis results in isolation of tritosylethanolamine 3a as a
byproduct.
Apparently, 3a was formed under transtosylation reaction of 1 by 2 with liberation of free
aziridine. Of interest, the attempt to prepare 3a from the reaction of equimolar quantities of 1 and
TsCl with aqueous KOH in benzene was unsuccessful. Only N-tosylaziridine (2) was obtained
under these conditions.
The conditions for the preparation of 3 as well as for the related salts were optimized.
Thus, compounds 3-7 may be obtained by direct substitution of tosyl group by corresponding N-
containing heterocycles. All the compounds were obtained at reflux of N,O-ditosylethanolamine
1
and corresponding heterocyclic compound (Schemes 3, 4). Compound 3 was obtained in
pyridine and 4-7 in toluene. The method developed in this work for the synthesis of pyridinium
salts includes only one stage; therefore, this way is very simple.
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
As it would be expected, the more nucleophilic (but no more basic, compare yields for 3
and 4) heterocycles give target compounds with higher yields than those with electron-
withdrawing groups. Furthermore, 2,6-dibromopyridine does not react with 1 even under
prolonged (more than 20 h) reflux in toluene.
In the case of imidazole a smooth formation of twice alkylated imidazolium salt 7 takes
place (Scheme 4). It may be separated from byproducts after double recrystallization from
13
ethanol. This compound was obtained both at 1:1 or 2:3 molar ratio of the reagents.
It should be noted that the course of these reactions is explained by presence of OTs group
(
effective leaving group). Furthermore, there is no reaction between pyridine and N-
tozylaziridine.
The compounds 3 and 3a were isolated in pure state; their structures were established on
1
13
the basis of Н, С NMR spectroscopy and X-ray analysis (Figs. 1, 2; Tables 1, 2).
In a crystal of 3 there is a strong hydrogen bond between the sulfonamide NH group in the
+
-
-
cation, [TsNHCH
2
CH
2
Py] , and sulfonato group SO
3
in the anion, [TsO] , that results in
interionic interaction. The formation of such hydrogen bonds may help related compounds to
bind with proteins in a solution. Furthermore such cationic analogs may be regarded as an
1
4
artificial receptors for recognition of biologically important anions which may form strong
-
-
- 15
hydrogen bonds (F , AcO , H
2
PO
4
). It should be noted that N(2) has an almost planar geometry
o
16
(
sum of angles is 359.55 ) similar to related neutral sulfonamides. The cation has a gauche-
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
o
conformation along the C-C bond (torsion angle N(1)-C-C-N(2) is 55.46 ) and staggered
o
conformation along the N—S bond (torsion angle C(11)-S-N-C(1) is -75 ) again similar to
1
7
neutral sulfonamides.
The main feature of 3a crystal structure is almost planar geometry of N atom (the average
o
angle sum is 359.88 for two independent molecules) possibly due to partial electron
delocalization between N, S and O atoms. The substituents along the C-C bond are situated in an
o
anti-conformation (torsion angles N-C-C-O are -177.85 and -172.08 ) and staggered
o
conformation along the N—S bond (torsion angles C-S-N-C are -77.69/-99.76 and 82.25/98.95 ).
The compound 3a is a colorless solid soluble in common organic solvents. All the salts
synthesized in this work are precipitated from toluene and insoluble in ether, THF, benzene,
partially soluble in CHCl
3
, CH
2
Cl , soluble in hot EtOH, water (except 5, 6), MeCN, DMSO.
2
Compound 5 is yellow, 6 is green and the others are colorless solids.
1
13
The structures of the compounds synthesized were confirmed by IR, H and C NMR
spectra and the compositions were established by elemental analysis data. For salts 3-7 the
MALDI-TOF mass spectra in positive ions mode contain the signals corresponding to the
1
pyridinium cations. The main feature of the H NMR spectra of 3-7 is the presence of two triplets
1
3
1
(
at 3.15-3.54 and 4.20-5.52 ppm) for two CH groups. In C NMR spectra (decoupled from H)
2
1
3
these groups appear in the fields 39.9-42.2 and 48.8-60.4 ppm, respectively. In C NMR spectra
of 3-7 the three sets of signals may be found. The first group includes the signals of the anionic
-
(
OTs ) part common for all compounds (approximately 125.5, 128.1, 137.8 and 145.5 ppm); the
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
second one is typical for the tosylamide part (approximately 126.5, 129.7, 137.0, 143.0 ppm) and
the last includes the signals of the corresponding heterocyclic cationic part.
In IR spectrum of 3a the bands of symmetric stretching vibration of sulfonamide and
-1
sulfonate groups may be distinguished and observed at 1168 (ν
the asymmetric stretching vibration are coalescent into broad band at 1371 cm (νas SO
SO ). Assignments of the SO -stretching bands are based on comparison with those of related
species .
The IR spectra for 3-7 contain strong absorptions for corresponding cation (typical for
s
SO
2
N), 1180 (ν
s
SO
3
) cm , but
-1
2
N and
3
3
1
8
-1
-1
SO
2
N group νas 1324-1332 cm and ν 1159-1161 cm ; the last bands were overlapped with
s
-1
-1
signals from anion) and tosylate anion (νas 1188-1207 cm and ν
s
1159-1161 cm which close to
1
9
-1
AgOTs in nujol, 1194 and 1152 cm ).
CONCLUSIONS
In summary, two unexpected products, 3 and 3a, during the synthesis of N-tosylaziridine
were isolated and characterized. The series of sulfonamide functionalized salts 3-7 was obtained
using very simple approach including the interaction of N,O-ditosylethanolamine with a number
of heterocyclic tertiary amines.
EXPERIMENTAL
General details
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Monoethanolamine (Aldrich) was distilled prior to use. Pyridine (Aldrich) was distilled
under KOH. Solvents were dried using standard procedures.
1
13
H NMR (400.130 MHz) and C NMR (100.613 MHz) spectra were recorded on Bruker
00 or Agilent 400 MR spectrometers at 298 K. Chemical shifts are given in ppm relative to
internal reference Me Si. MALDI mass spectra were recorded on Autoflex II Bruker (FWHM
4
4
resolution 18000) equipped with a nitrogen laser with a wavelength of 337 nm and a TOF mass
analyzer operating in reflectron mode. The accelerating voltage is 20 kV. Samples were applied
to a substrate made of polished steel. The spectra were recorded in the positive ion mode. The
resulting spectrum was the sum of 300 spectra obtained at different points of the sample. 2,5-
Dihydroxybenzoic acid (DHB) (Acros, 99%) and α-cyano-4-hydroxycinnamic acid (HCCA)
(
Acros, 99%) were used as the matrices. Elemental analyses were carried out by the
Microanalytical Laboratory of the Chemistry Department of the Moscow State University using
Heraeus Vario Elementar instrument. Melting points were measured on a WRS-2A melting point
1
13
apparatus and are uncorrected. The Supplewnmwntal Materials contains selected H and
C
NMR spectra of products 1-7 (Figures S 1 – S 16)
Synthesis of compounds 1, 2, 3 and 3a
N-[2-[(p-Tolylsulfonyl)oxy]ethyl]-p-tolylsulfonamide (1)
Monoethanolamine (12.00 g, 0.197 mol) was dissolved in anhydrous pyridine (15 mL) and
o
cooled to 0 C in a bath of ice and salt. Tosyl chloride (80.00 g, 0.419 mol), finely powdered,
o
was suspended in pyridine (50 mL) and cooled to -50 C. The ethanolamine solution was added
o
while the temperature was maintained below 10 C for 30 min. The mixture was kept at room
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
o
temperature for 6 h and then at 4 C overnight. The mixture was poured, with stirring, on crushed
ice (500 g) and acidified with glacial acetic acid (20 mL), whereupon the oily material solidified.
The solid was crushed to a slurry in water, collected, and washed with water. The product was
dried in desiccator over P
2
O
5
in vacuum. Recrystallization of the crude product (69 g) from hot
(200 mL) gave 1 as a white powder (55.00 g, 76
), mp 87-88 C, mp 86-87 C. H NMR (400.130 MHz, CDCl ): δ 2.41 (s, 3Н, Me), 2.44 (s,
Н, Me), 3.18-3.22 (m, 2Н, CH ), 4.03 (t, J= 5.3 Hz, 2Н, CH ), 5.00 (br s, 1H, NH), 7.27 (d, J=
.3 Hz, 2H, p-C ), 7.33 (d, J= 8.3 Hz, 2H, p-C ), 7.68 (d, J= 8.3 Hz, 2H, p-C ), 7.73 (d,
) ppm; C NMR (100.613 MHz, CDCl ): δ 21.4, 21.6 (2Me), 42.0, 68.7
), 127.0, 127.9, 129.8, 130.0, 132.2, 136.6, 143.7, 145.2 (2C ) ppm.
It should be noted that prolonged storage of the reaction mixture for 3-4 days results in
chloroform (50 mL) and addition of cold CCl
4
o
o
20 1
%
3
3
2
2
8
6
H
4
H
6 4
6
H
4
1
3
J= 8.3 Hz, 2H, p-C
6
H
4
3
(
2CH
2
6
H
4
appearance of crystals of 3 (up to 8 %; see below) which may be isolated by filtration.
N-Tosylaziridine (2)
The compound was obtained from 1 (13.00 g, 0.035 mol) in benzene (200 mL) at treatment
2
1
with 20 % aq. KOH (50 mL) using literature procedure. Evaporation of the volatile materials
о
should be performed at temperatures below 50 С. The crude material was recrystallized from
о
о
21 1
ethylacetate, giving 2 (6.20 g, 90 %), mp 65-66 С, mp 63-64 С. H NMR (400.130 MHz,
CDCl ): δ 2.35 (br s, 4Н, СН СН ), 2.43 (s, 3Н, СН ), 7.33 (d, J= 8.3 Hz, 2Н, C ), 7.81 (d, J=
). C NMR (100.613 MHz, CDCl ): δ 21.5 (СН ), 27.3 (СН ), 127.9, 129.6,
).
3
2
2
3
6
H
4
13
8
1
.3 Hz, 2Н, C
6
H
4
3
2
3
34.8, 144.6 (C
6
H
4
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
It should be noted that 3a (0.36 g, 2%) was isolated as a colorless crystals from mother
о
1
liquir, mp 146-147 С. H NMR (400.130 MHz, CDCl
3
): δ 2.44 (s, 9H, 3Me), 3.91 (t, J = 6.1 Hz,
2
8
Н, CH
2
), 4.15 (t, J= 6.1 Hz, 2Н, CH
), 7.86 (d, J= 8.3 Hz, 4H, p-C
), 127.9, 129.9, 132.3, 145.1 (OTs), 128.5, 129.7, 136.0, 145.3 (NTs
2
), 7.32 (d, J= 7.8 Hz, 6H, aromatic hydrogens), 7.67 (d, J=
1
3
.1 Hz, 2H, p-C
6
H
4
H
6 4
). C NMR (100.613 MHz, CDCl
3
): δ 21.6
). IR
(
(
Me), 46.4, 67.6 (2CH
2
2
-1
nujol): 1595, 1371, 1180, 1168, 1083, 1051, 991, 862, 659, 551 cm . MS (MALDI-TOF):
+
C
23
H25NO
7
S
3
[M] calcd.: 523.6, observed: 523.8. Anal. Calcd for C23
H
25NO
7
3
S : C, 52.75; H,
4
.81; N, 2.67; S, 18.37. Found: C, 52.82; H, 4.72; N, 2.57; S, 18.43.
-(2-(p-Tolylsulfonamido)ethyl)pyridinium p-tolylsulfonate (3)
A mixture of 1 (7.38 g, 0.020 mol) and pyridine (40 mL) was refluxed for 8 h. The reaction
mixture was cooled to room temperature and pyridine was evaporated to half the volume. Then
1
CHCl
3
(20 mL) was added, and the residue was filtered off, washed by CHCl and dried.
3
o
o
12b
Compound 3 was obtained as a crystalline solid (8.70 g, 97 %), mp 182 C, mp 180 C. IR
-1
(
nujol): 3070, 1625, 1492, 1326, 1205, 1186, 1160, 1122, 1090, 1033, 1011, 813, 682, 565 cm .
1
H NMR (400.130 MHz, DMSO-d
H, CH ), 4.65 (t, J=5.3 Hz, 2H, CH
p-C
6
): δ 2.27 (s, 3H, Me), 2.36 (s, 3H, Me), 3.32 (t, J= 5.3 Hz,
), 7.10 (d, J= 7.8 Hz, 2H, p-C ), 7.35 (d, J= 8.2 Hz, 2H,
), 7.58 (d, J= 8.2 Hz, 2H, p-C ), 7.94 (br s, 1H, NH),
2
2
2
6
H
4
6
H
4
), 7.49 (d, J= 7.8 Hz, 2H, p-C
6
H
4
6
H
4
+
+
+
13
8
.14 (t, J= 7.0 Hz, 2H, Py ), 8.60 (t, J= 7.6 Hz, 1H, Py ), 8.99 (d, J= 5.9 Hz, 2H, Py ) ppm; C
NMR (100.613 MHz, DMSO-d
6
): δ 20.8, 20.9 (2Me), 42.8, 60.4 (2CH
2
), 125.5, 128.1, 137.7,
-
+
1
45.5 (MeC
6
H
4
SO
3
), 126.4, 129.7, 137.0, 143.0 (MeC
6
H
4
SO
2
NH), 127.8, 145.2, 145.8 (Py )
+
ppm. MS (MALDI-TOF): C14
H
17
N
2
O
2
S [(M)-OTs] calcd.: 277.4, observed: 277.2. Anal. Calcd
1
0
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
for C21
H
24
N
2
O
5
S : C, 56.23; H, 5.39; N, 6.25; S, 14.30. Found: C, 56.07; H, 5.21; N, 6.19; S,
2
1
3.89.
General procedure for salts 4-7 synthesis
A mixture of 1 (7.38 g, 0.020 mol) and heterocyclic amine (0.030 mol) in toluene (50 mL)
was refluxed for required period. The reaction mixture was cooled to room temperature. The
residue was filtered off, washed by toluene and dried. Recrystallization from ethanol gave a pure
product.
2
,6-Dimethyl-1-(2-(p-Tolylsulfonamido)ethyl)pyridinium p-tolylsulfonate (4)
o
Yield 33 %, colorless crystals, mp 198 C; IR (nujol): 3075 br, 2854, 1627, 1495, 1324,
-
1 1
1
d
6
8
1
2
1
205, 1188, 1161, 1122, 1093, 1033, 1010, 815, 680, 567 cm . H NMR (400.130 MHz, DMSO-
): δ 2.27 (s, 3H, Me), 2.36 (s, 3H, Me), 2.83 (s, 6H, 2Me), 3.24-3.32 (m, 2H, CH ), 4.59 (t, J=
.6 Hz, 2H, CH ), 7.09 (d, J= 7.8 Hz, 2H, p-C ), 7.37 (d, J= 8.1 Hz, 2H, p-C ), 7.46 (d, J=
.1 Hz, 2H, p-C ), 7.65 (d, J= 8.1 Hz, 2H, p-C ), 7.85 (d, J= 7.9 Hz, 2H, Py ), 8.08 (br s,
6
2
2
6
H
4
6
H
4
+
6
H
4
6
H
4
+
13
H, NH), 8.30 (t, J= 7.9 Hz, 1H, Py ) ppm; C NMR (100.613 MHz, DMSO-d ): δ 20.7, 20.9,
6
-
1.0 (3Me), 39.9, 52.2 (2CH
2
), 125.4, 128.0, 137.6, 143.0 (CH
3
C
6
H
4
SO
3
), 126.4, 129.7, 137.2,
+
45.6 (CH SO
3
C
6
H
4
2
NH), 127.7, 144.6, 156.0 (Py ) ppm. MS (MALDI-TOF): C16
H
21
N
2
2
O S
+
[
(M)-OTs] calcd.: 305.4, observed: 305.1. Anal. Calcd for C23
H
28
N
2
O
5
2
S : C, 57.96; H, 5.92; N,
5
.88; S, 13.46. Found: C, 57.84; H, 5.81; N, 5.87; S, 13.26.
1
-(2-(p-Tolylsulfonamido)ethyl)quinolinium p-tolylsulfonate (5)
o
Yield 72 %, pale yellow crystals, mp 149 C; IR (nujol): 3560 br, 3090 br, 1640, 1597,
-1 1
1
527, 1324, 1201, 1195, 1160, 1122, 1095, 1033, 1010, 820, 728, 682, 567, 553 cm . H NMR
1
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
(
400.130 MHz, DMSO-d
6
): δ 2.26 (s, 3H, Me), 2.31 (s, 3H, Me), 3.39 (t, J= 5.3 Hz, 2H, CH
2
4
),
),
5
7
8
8
C
.12 (t, J= 5.3 Hz, 2H, CH ), 7.09 (d, J= 8.2 Hz, 2H, p-C ), 7.22 (d, J= 7.8 Hz, 2H, p-C H
2
6
H
4
6
.42 (d, J= 8.2 Hz, 2H, p-C
6
H
4
), 7.50 (d, J= 7.8 Hz, 2H, p-C
6
H
4
), 7.96 (t, J= 5.5 Hz, 1H, NH),
+
+
+
.02 (t, J= 7.6 Hz, 1H, C
9
H
7
N ), 8.14-8.27 (m, 2H, C
9
H
7
N ), 8.46 (d, J= 7.4 Hz, 1H, C
9
H
7
N ),
+
+
.54 (d, J= 9.0 Hz, 1H, C
9
H
7
N ), 9.28 (d, J= 8.2 Hz, 1H, C
9
H
7
N ), 9.38 (d, J= 4.7 Hz, 1H,
+
13
9
H
7
N ) ppm; C NMR (100.613 MHz, DMSO-d
6
): δ 20.8, 20.9 (2Me), 41.5, 57.0 (2CH
2
),
-
1
1
25.5, 128.1, 137.7, 145.5 (CH
3
C
6
H
4
SO
3
), 126.1, 129.6, 136.8, 142.9 (CH
3
C
6
H
4
SO
2
NH), 118.6,
+
21.8, 129.7, 129.7, 130.8, 135.6, 137.5, 147.9, 150.4 (C
9
H
7
N ) ppm. MS (MALDI-TOF):
+
C
18
H
19
N
2
O
2
S [(M)-OTs] calcd.: 327.4, observed: 327.1. Anal. Calcd for C25
H
26
N
2
O
5
2
S : C,
6
0.22; H, 5.26; N, 5.62; S, 12.86. Found: C, 60.02; H, 5.42; N, 5.51; S, 12.16.
1
0-(2-(p-Tolylsulfonamido)ethyl)acridinium p-tolylsulfonate (6)
o
Yield 11 %, green crystals, mp 217 C; IR (nujol): 3563, 3092, 1597, 1529, 1326, 1203,
-
1 1
1
d
7
162, 1122, 1090, 1033, 1010, 817, 732, 683, 565, 558 cm . H NMR (400.130 MHz, DMSO-
): δ 2.27 (s, 3H, Me), 2.30 (s, 3H, Me), 3.50-3.60 (m, 2H, CH ), 5.51 (t, J= 5.0 Hz, 2H, CH ),
.09 (d, J= 7.8 Hz, 2H, p-C ), 7.15 (d, J= 7.8 Hz, 2H, p-C ), 7.32 (d, J= 7.8 Hz, 2H, p-
), 7.94 (t, J= 6.4 Hz, 1H, NH), 8.01 (t, J= 7.4 Hz, 2H,
6
2
2
6
H
4
6
H
4
C
C
6
H
4
), 7.50 (d, J= 7.8 Hz, 2H, p-C
6
H
4
+
+
+
13
H
9
N ), 8.42 (t, J= 7.7 Hz, 2H, C13
H
9
N ), 8.60 (d, J= 8.1 Hz, 2H, C13
H N ), 8.70 (d, J= 9.1
9
+
+
13
Hz, 2H, C13
H
9
N ), 10.16 (s, 1H, C13
H
9
N ) ppm; C NMR (100.613 MHz, DMSO-d ): δ 20.7,
6
-
2
1
0.9 (2Me), 41.1, 49.4 (2CH
2
), 125.5, 128.0, 137.7, 145.6 (CH
3
C
6
H
4
SO
3
), 126.0, 129.5, 136.8,
+
42.9 (CH
3
C
6
H
4
SO
2
NH), 118.1, 126.4, 127.7, 131.9, 139.2, 141.2, 151.5 (C13
H
9
N ) ppm. MS
+
(
MALDI-TOF): C22
H
21
N
2
O
2
S [(M)-OTs] calcd.: 377.5, observed: 377.3. Anal. Calcd for
C
29
H
28
N
2
O
5
S : C, 63.48; H, 5.14; N, 5.11; S, 11.69. Found: C, 63.36; H, 5.08; N, 5.12; S, 11.54.
2
1
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
,3-Bis(2-(p-tolylsulfonamido)ethyl)-1H-imidazol-3-ium p-tolylsulfonate (7)
o
Yield 76 %, colorless crystals, mp 140 C; IR (nujol): 3482 br, 3239, 3064 br, 1596, 1562,
-
1 1
1
332, 1305, 1216, 1203, 1159, 1122, 1087, 1033, 1010, 925, 814, 746, 684, 563, 555 cm . H
NMR (400.130 MHz, DMSO-d ): δ 2.27 (s, 3H, Me), 2.37 (s, 6H, Me), 3.16 (q, J= 6.0 Hz, 4H,
CH ), 3.36 (br s, 2H, 2NH), 4.21 (t, J= 6.0 Hz, 4H, CH ), 7.10 (d, J= 7.9 Hz, 2H, p-C ), 7.38
), 7.64 (d, J= 8.3 Hz, 4H, p-C ),
) ppm; С NMR (100.613
6
2
2
6
H
4
(
d, J= 8.1 Hz, 4H, p-C
6
H
4
), 7.49 (d, J= 7.9 Hz, 2H, p-C
6
H
4
6
H
4
+
+
13
7
.67 (d, J= 1.5 Hz, 1H, C
3
H
4
N
2
), 7.82 (t, J= 6.1 Hz, 1H, C
3
H
4
N
2
MHz, DMSO-d
6
): δ 20.8, 21.0 (2Me), 42.2, 48.8 (2CH
2
), 125.5, 128.1, 137.8, 145.5
-
+
(
(
CH
3
C
6
H
4
SO
3
), 126.5, 129.8, 137.0, 143.0 (CH
3
C
6
H
4
SO
2
NH), 122.7, 136.8 (C
3
H
4
N
2
) ppm. MS
+
MALDI-TOF): C21
H
27
N
4
O
4
S
2
[(M)-OTs] calcd.: 463.6, observed: 463.1. Anal. Calcd for
C
19
H
23
N
3
O
5
S : C, 52.16; H, 5.30; N, 9.60; S, 14.66. Found: C, 52.26; H, 5.26; N, 9.42; S, 14.47
2
X-RAY CRYSTALLOGRAPHY
Experimental intensities for 3 and 3a were measured on a Bruker SMART APEX II
diffractometer (graphite monochromatized Mo-Kα radiation, λ=0.71073 Å) at 150 K using 
scan mode. The structures were solved by direct methods and refined by full matrix least-squares
2
22
on F (SHELXTL ) with anisotropic thermal parameters for all non-hydrogen atoms. All
hydrogen atoms (except amino atom H2 in 3) were placed in calculated positions and refined
using a riding model. In 3, amino hydrogen atom H2 was found from difference map and refined
isotropically. The studied crystal of 3 represented non-merohedral twinning (matrix 1 0 0 0 -1 0
0
0 -1) with domain ratio 0.76 / 0.24. Crystallographic data for compounds 3 and 3a are given in
Table 1.
1
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
The crystallographic data for the structures of compounds 3 and 3a have been deposited with
the Cambridge Crystallographic Data Centre as Supplementary Publication under the CCDC
numbers 1037300 and 1037301. They can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
ACKNOWLEDGMENTS
This work is supported by the RFBR (12-03-00206-а) and by President Grant for Young Russian
Scientists (MD-3634.2012.3). This work was supported in part by M.V. Lomonosov Moscow
State University Program of Development.
SUPPLEMENTARY MATERIALS
1
13
Supplementary data ( H, C NMR spectra and CIF files for 3 and 3a) associated with this article
are available free of charge via the journal’s website.
1
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
REFERENCES
1
. (a) Moss, T. A.; Barber, D. M.; Kyle, A. F.; Dixon, D. J. Chem. Eur. J. 2013, 19, 3071-3081.
(
b) Stamm, H. J. Prakt. Chem. 1999, 341, 319-331. (c) Tanner, D. Angew. Chem., Int. Ed. Engl.
1
2
3
994, 33, 599-619. (d) Hu, X. E. Tetrahedron, 2004, 60, 2701-2743.
. Duggan, M. E.; Karanewsky, D. S. Tetrahedron Lett. 1983, 24, 2935-2938.
. (a) Herges, R.; Dikmans, A.; Jana, U.; Köhler, F.; Jones, Peter G.; Dix, I.; Fricke, T.; König,
B. Eur. J. Org. Chem. 2002, 3004-3014. (b) Zhang, Z.; Mikkola, S.; Lonnberg, H. Org. Biomol.
Chem. 2003, 1, 854-858.
4
5
. Chandrasekhar, S.; McAuley, A. J. Chem. Soc., Dalton Trans. 1992, 2967-2970.
. (a) Park, S. E.; Nam, E. H.; Jang, H. B.; Oh, J. S.; Some, S.; Lee, Y. S.; Song, C. E. Adv.
Synth. Catal. 2010, 352, 2211-2217. (b) Hara, N.; Nakamura, S.; Sano, M.; Tamura, R.;
Funahashi, Y.; Shibata, N. Chem. Eur. J. 2012, 18, 9276-9280.
6
. (a) Schwarz, A. D.; Chu, Z.; Mountford, P. Organometallics 2010, 29, 1246-1260. (b)
Dell’Acqua, M.; Castano, B.; Cecchini, C.; Pedrazzini, T.; Pirovano, V.; Rossi, E.; Caselli, A.;
Abbiati, G. J. Org. Chem. 2014, 79, 3494-3505.
7
. (a) Schmidtchen, F. P.; Berger, M. Chem. Rev. 1997, 97, 1609-1646. (b) Amendola, V.;
Fabbrizzi, L.; Mosca, L.; Schmidtchen, F.-P. Chem. Eur. J. 2011, 17, 5972-5981. (c) Sakai, R.;
Barasa, E. B.; Sakai, N.; Sato, S.-i.; Satoh, T.; Kakuchi, T. Macromolecules 2012, 45, 8221-
8
227. (d) Gale, P. A.; Busschaert, N.; Haynes, C. J. E.; Karagiannidis, L. E.; Kirby, I. L. Chem.
Soc. Rev. 2014, 43, 205-241.
1
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
8
. (a) Chelouf, H.; Berredjem, M.; Boufas, W.; Bouchareb, F.; Djahoudi, A.; Aouf, N.-E.
Phosphorus, Sulfur Silicon Relat. Elem. 2014, 189, 1396-1404. (b) Li, H.-Q.; Yang, J.; Ma, S.;
Qiao, C. Bioorg. Med. Chem. 2012, 20, 4194-4200.
9
1
1
2
1
. Dixon, R.A.; Given, B. D. 2007 U.S. Patent WO 2007106494.
0. Elder, M. J.; Leonard, J.; Dart, J. K. Br. J. Ophthalmol. 1996, 80, 549-552.
1. Shen, C.-H.; Wang, Y.-F.; Kovalevsky, A. Y.; Harrison, R. W.; Weber, I. T. FEBS J. 2010,
77, 3699-3714.
2. (a) Kotadia, D. A.; Soni, S. S. Catal. Sci. Technol. 2013, 3, 469-474. (b) Saravanamurugan,
S.; Fehrmann, R.; Riisager, A. Synth. Commun. 2012, 42, 3383-3394.
1
6
1
3. Vlahakis, J. Z.; Lazar, C.; Crandall, I. E.; Szarek, W. A. Bioorg. Med. Chem. 2010, 18, 6184-
196.
4. (a) Chakraborty, A.; Gunupuru, R.; Maity, D.; Patra, S.; Suresh, E.; Paul, P. Inorg. Chem.
Commun. 2010, 13, 1522-1526. (b) Fuentes de Arriba, A. L.; Turiel, M. G.; Simon, L.; Sanz, F.;
Boyero, J. F.; Muniz, F. M.; Moran, J. R.; Alcazar, V. Org. Biomol. Chem. 2011, 9, 8321-8327.
1
1
5. Shang, X.-F.; Li, J.; Lin, H.; Jiang, P.; Cai, Z.-S.; Lin, H.-K. Dalton Trans. 2009, 2096-2102.
6. Altamura, M.; Fedi, V.; Nannicini, R.; Paoli, P.; Rossi, P. Acta Crystallogr., Sect. E 2012, 68,
o3308-o3309.
7. (a) Baldauf, C.; Günther, R.; Hofmann, H.-J. J. Mol. Struct.: THEOCHEM 2004, 675, 19-28.
b) Sarojini, K.; Krishnan, H.; Kanakam, C. C.; Muthu, S. Spectrochim. Acta, Part A 2012, 96,
57-667.
1
(
6
1
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
8. (a) Mondelli, M.; Pavan, F.; de Souza, P. C.; Leite, C. Q.; Ellena, J.; Nascimento, O. R.;
Facchin, G.; Torre, M. H. J. Mol. Struct. 2013, 1036, 180-187. (b) Gulea, A. P.; Spynu, S. N.;
Tsapkov, V. I.; Poirier, D.; Roy, J. Russ J. Gen. Chem. 2006, 76, 1458-1463.
1
4
2
2
2
9. Weinert, C. S.; Prokopuk, N.; Arendt, S. M.; Stern, C. L.; Shriver, D. F. Inorg. Chem. 2001,
0, 5162-5168.
0. Hope, D. B.; Horncastle, K. C. J. Chem. Soc. C 1966, 1098-1101.
1. Martin, A. E.; Ford, T. M.; Bulkowski, J. E. J. Org. Chem. 1982, 47, 412-415.
2. Sheldrick, G.M. Acta. Crystallogr. Sect. A, 2008, A64, 112-122.
1
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
TABLE 1 Crystal Structure and Data Refinement Parameters for compounds 3 and 3a
3
3a
+
empirical formula
[C14
H
17
N
2
O
O S]
3
2
S] [C
7
H
7
C
23
H
25NO
S
7 3
-
M
w
448.54
160(2)
523.62
150(2)
temperature (K)
size (mm)
color/shape
cryst. system
space group
a (Å)
0.40 x 0.14 x 0.12
colourless/block
monoclinic
0.35 x 0.20 x 0.15
colourless/ nugget
monoclinic
P2
1
/c
P2 /n
1
7.895(3)
25.476(9)
10.478(4)
90.373(5)
2107.3(13)
4
19.7687(9)
12.5493(6)
19.8293(9)
102.917(1)
4794.8(4)
8
b (Å)
c (Å)
β (deg)
3
V (Å )
Z
-3
ρ
cald (g*cm )
1.414
1.451
-
1
abs coeff. (mm )
F(000)
0.289
0.354
944
2192
θ range (deg)
0.80 - 26.00
10359 / 3650
2.11 - 27.00
45178 / 8089
no. of collected/unique
rflns.
R
int
0.0502
4085 / 0 / 278
1.144
0.0523
10446 / 0 / 619
1.016
data/restraints/params.
2
goodness of fit on F
final R indices (I > 2σ(I))
R
1
1
= 0.0556, wR
2
=
=
R
1
= 0.0420, wR
0.1049
2
=
=
0
.1478
= 0.0644, wR
.1587
0.331 / 0.071
R indices (all data)
R
2
R
1
= 0.0587, wR
0.1150
2
0
largest diff. peak/hole
0.669 / 0.058
3
(
e/Å )
1
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
TABLE 2 Selected bond lengths (Å) and angles (deg) for compounds 3 and 3a
Compound 3
S(1)-N(2)
1.599(3)
123.2(3)
C(1)-N(2)-S(1)
Hydrogen bond N(2)-H…O(22)
d(N-H)
d(H…O)
d(N…O)
O-H-O
0.81(5)
2.09(5)
2.863(5)
154(4)
Compound 3a
S(2)-N(1)
S(3)-N(1)
S(5)-N(2)
S(6)-N(2)
1.6739(18)
1.6870(17)
1.686(2)
1.6789(19)
117.29(14)
119.27(14)
123.31(10)
116.65(15)
120.24(15)
123.00(11)
C(2)-N(1)-S(2)
C(2)-N(1)-S(3)
S(2)-N(1)-S(3)
C(4)-N(2)-S(6)
C(4)-N(2)-S(5)
S(6)-N(2)-S(5)
1
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
FIGURE 1 Molecular structure of 3. Displacement ellipsoids are shown at 50%
probability level.
2
0
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
FIGURE 2 Molecular structure of 3a. Only one independent molecule is presented.
Displacement ellipsoids are shown at 50% probability level.
2
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
SCHEME 1 Synthesis of N-tosylaziridine.
2
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
SCHEME 2 Synthesis of ditosyl- and tritosylethanolamine.
2
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
SCHEME 3 Synthesis of compounds 3-6.
2
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
SCHEME 4 Synthesis of imidazolium salt 7.
2
5
ACCEPTED MANUSCRIPT