Characterization and synthesis of O- and N-tosylated N,N-bis(2-aminophenyl)isophthalamide based ligands

Article abstract of DOI:10.1016/j.molstruc.2009.09.015

A synthetic strategy for the preparation of O- and N-tosylated N,N-bis(2-aminophenyl)isophthalamide based ligands is described. It was observed that selectivity in O- and N-tosylation could be achieved by performing the reaction at low temperatures in the

Full text of DOI:10.1016/j.molstruc.2009.09.015

Journal of Molecular Structure 938 (2009) 137–141
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Characterization and synthesis of O- and N-tosylated N,N-bis(2-aminophenyl)
isophthalamide based ligands
*
Kirsi Salorinne, Katri Toikkanen, Maija Nissinen
Department of Chemistry, Nanoscience Center, University of Jyväskylä, P.O. Box 35, 40014 JYU, Finland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 July 2009
Received in revised form 3 September 2009
Accepted 11 September 2009
Available online 18 September 2009
A synthetic strategy for the preparation of O- and N-tosylated N,N-bis(2-aminophenyl)isophthalamide
based ligands is described. It was observed that selectivity in O- and N-tosylation could be achieved by
performing the reaction at low temperatures in the presence of an appropriate base. The obtained O-
and N-tosylated products were characterized by means of NMR and mass spectroscopy, and X-ray
crystallography.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Tosylation
NMR spectroscopy
X-ray crystallography
1. Introduction
ize the formed HCl in the tosylation reaction. Therefore, the role of
the base was considered significant in terms of creating disparity
Tosylation (or sulfonylation) of alcohols is one of the most ver-
satile reactions in organic chemistry, which is widely used as an
intermediate step due to the easy conversion of tosylates (or sulfo-
nates) into ethers, nitriles or alkylhalides [1]. Amines also undergo
tosylation reaction to form sulfonamides [2], although, it is usually
intended to serve as a protecting group rather than a good leaving
group as is the case with alcohols. High regioselectivity is often re-
quired in the tosylation reaction since tosylates are typically used
as intermediates in the synthesis of complicated organic molecules
[1]. In fact, there are many different methods developed to obtain
selectivity in the tosylation of primary and secondary alcohols, but
there are only few examples in the literature of selective O- or N-
tosylation when there are both hydroxyl and amine functionality
within the same molecule [3].
During our ongoing research to synthesize supramolecular
receptor molecules [4], we came across to a difficult task, which
entailed a selective tosylation of a hydroxyl group in a ligand that
contained both amine and amide functionality. After unsuccessful
and tedious protection and deprotection efforts, we started to look
for a way to discriminate the functional groups from one another
according to their abilities to act as a nucleophile needed in the
tosylation reaction. In the case of the hydroxyl group, a base is
needed to deprotonate the hydroxyl hydrogen in order to form a
reactive nucleophile, whereas, the neutral amine can function as
a nucleophile on its own and the function of the base is to neutral-
between the different functional groups. It was found that depend-
ing on the base used in the reaction, and performing the deproto-
nation step at low temperatures before introducing the tosylating
agent in the reaction, selectivity between O- and N-tosylation
was achieved. In this paper we report the synthesis and tosylation
of ligand 2 and the characterization of the formed bistosylated
products.
2. Experimental section
2.1. General
1H, 13C, 15N, COSY, HMQC and HMBC NMR spectra were re-
corded on a Bruker Avance DRX 500 spectrometer and chemical
shifts were calibrated to the residual proton and carbon resonance
of the solvent. ESI mass spectra were measured with Micromass
LCT ESI-TOF instrument. Elemental analyses were determined with
Vario EL III instrument. Melting points were measured in open cap-
illaries with a Stuart Scientific SMP3 melting point apparatus and
are uncorrected. o-Amino-N-(2-hydroxyethyl)aniline (1) was pre-
pared according to literature procedure [5]. All other reagents used
were commercial unless otherwise noted. THF was distilled over
sodium/benzophenone under argon atmosphere prior use.
2.2. Synthesis of compound 2
o-Amino-N-(2-hydroxyethyl)aniline [5] (2.0 g, 13 mmol) was
dissolved in dry THF (80 mL) under N2 atmosphere and cooled to
* Corresponding author. Tel.: +358 14 260 4242; fax: +358 14 260 4756.
E-mail address: maija.nissinen@jyu.fi (M. Nissinen).
0022-2860/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2009.09.015

138
K. Salorinne et al. / Journal of Molecular Structure 938 (2009) 137–141
ꢀ70 °C. Triethylamine (1.8 mL, 13 mmol) was added and the reac-
tion mixture was stirred at/below ꢀ70 °C for 15 min before the
dropwise addition of isophthaloyl dichloride (1.3 g, 6.4 mmol) in
dry THF (20 mL). After the addition was complete the reaction mix-
ture was allowed to warm to room temperature and stirred over-
night. Solvent was removed by rotavapor. Water was added to
the yellowish residue and stirred for 30 min. The white solid was
collected by suction filtration and dried in vacuum. Yield 2.3 g
(83%) of white powdery solid. 1H NMR: (DMSO-d6, 500 MHz) d
9.78 (s, NHCO, 2H), 8.59 (s, e, 1H), 8.17 (d, J = 7.32 Hz, f, 2H), 7.67
(t, J = 7.70 Hz, g, 1H), 7.17 (d, J = 7.30 Hz, d, 2H), 7.11 (t,
J = 7.02 Hz, b, 2H), 6.74 (d, J = 7.21 Hz, a, 2H), 6.65 (t, J = 7.51 Hz,
c, 2H), 5.01 (t, J = 5.63 Hz, NH, 2H), 4.69 (t, J = 5.42 Hz, OH, 2H),
3.58 (q, J = 5.74 Hz, i, 4H), 3.15 (q, J = 5.81 Hz, h, 4H) ppm. 13C
NMR: (DMSO-d6, 126 MHz) d 165.2 (NHCO), 143.7 (a0), 134.7 (f0),
130.5 (f), 128.3 (g), 127.3 (e), 127.2 (d), 127.1 (b), 123.3 (d0),
115.7 (c), 111.1 (a), 59.5 (i), 45.5 (h) ppm. MS (ESI-TOF): m/z
435.17 [M + H]+. Anal. Calcd. for C24H26N4O4ꢁ0.75 H2O: C, 64.34;
H, 6.19; N, 12.51. Found: C, 64.58; H, 6.13; N, 12.39. mp. 176–
177 °C.
J = 1.33 Hz, d, 1H), 8.22 (d, J = 8.01 Hz, f, 1H), 8.15 (d, J = 8.08, f, 1H),
7.75 (d, J = 8.34 Hz, ArTs, 2H), 7.71 (t, J = 7.80 Hz, g, 1H), 7.54 (d,
J = 8.27 Hz, ArTs, 2H), 7.43 (td, J = 7.12 and J = 1.41 Hz, c, 1H),
7.36 (d, J = 8.09 Hz, ArTs, 4H), 7.19 (d, J = 7.47 Hz, d, 1H), 7.10–
7.05 (m, b, 2H), 6.70 (dd, J = 6.95 and J = 1.40 Hz, a, 1H), 6.68–
6.63 (m, c/a, 2H), 4.11 (t, J = 5.81 Hz, h/i, 3H), 3.62 (m, i, 1H), 3.39
(t, J = 5.79 Hz, h, 2H), 3.17 (m, h/i, 2H), 2.38 (s, TsMe, 3H), 2.35 (s,
TsMe, 3H) ppm. 13C NMR: (DMSO-d6, 126 MHz) d 165.0 (NHCO),
163.8 (NHCO), 144.8 (Ts0), 143.7 (Ts0), 142.8 (a0), 138.6 (d0), 135.3
(Ts0), 134.9 (f0), 134.5 (f0), 132.1 (Ts0), 130.9 (f), 130.0 (Ts), 129.7
(Ts), 129.2 (f), 129.1 (c/a0), 128.5 (g), 128.2 (a), 127.5 (Ts/Ts),
127.4 (e/d), 127.0 (b), 124.4 (b), 123.5 (d0), 122.0 (d), 116.2 (c),
110.8 (a), 68.7 (i), 57.7 (i), 53.7 (h), 41.5 (h), 21.0 (TsMe), 20.7
(TsMe) ppm. MS (ESI-TOF): m/z 743.21 [M + H]+.
2.4. Crystal structure determination
Data were recorded on a Nonius Kappa CCD diffractometer with
Apex II detector using graphite monochromatized CuK
a
[k(CuK ) = 1.54178 Å] radiation. The data was processed with Den-
a
zo-SMN v0.97.638 [6]. The structure was solved by direct methods
(SHELXS-97 [7]) and refinement based on F2 was made by full-ma-
trix least-squares techniques (SHELXL-97 [8]). The hydrogen atoms
were calculated to their idealized positions with isotropic temper-
ature factors (1.2 or 1.5 times the temperature of factor the parent
atom) and refined as riding atoms except for the amide and hydro-
xyl hydrogens, which were located from the difference Fourier
map. Absorption correction [9] was made but not used, since it
worsened the R-value. The crystallographic parameters are dis-
played in Table 1. Ortep [10] and ViewerLite [11] were used to pre-
pare the figures. Crystallographic data (excluding structure factors)
for the structure in this paper have been deposited with the Cam-
bridge Crystallographic Data Center as supplementary publication
No. CCDC-718828. Copies of the data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif.
2.3. General procedure for the tosylation of compound 2
Ligand 2 (200 mg, 0.46 mmol) was dissolved in dry THF (40 mL)
under N2 atmosphere and cooled to ꢀ70 °C. Base (1.0 mmol) was
added in one portion and the reaction mixture was stirred at/
below ꢀ70 °C for 15 min before the dropwise addition of p-tolu-
enesulfonyl chloride (190 mg, 1.0 mmol) in THF (20 mL). After
the addition was complete, the reaction mixture was allowed to
warm to room temperature and stirred for 2 days. Solvent was re-
moved under vacuum. Purification by Flash chromatography on
silica using ethyl acetate–chloroform (2:8 ? 8:2) as the eluent.
2.3.1. Compound 3a
White solid. mp. 252–254 °C. 1H NMR: (DMSO-d6, 500 MHz) d
9.96 (s, NHCO, 2H), 8.56 (s, e, 1H), 8.32 (dd, J = 7.20 and
J = 1.03 Hz, d, 2H), 8.16 (dd, J = 6.08 and J = 1.78 Hz, f, 2H), 7.71 (t,
J = 7.76 Hz, g, 1H), 7.54 (d, J = 8.27 Hz, ArTs, 4H), 7.44 (td, J = 7.11
and J = 1.45 Hz, c, 2H), 7.34 (d, J = 7.98 Hz, ArTs, 4H), 7.10 (td,
J = 6.24 and 1.45 Hz, b, 2H), 6.74 (dd, J = 6.63 and 1.32 Hz, a, 2H),
5.57 (t, J = 4.48 Hz, OH, 2H), 4.15 (m, h, 2H), 3.64 (m, i, 2H), 3.19
(m, h/i, 4H), 2.36 (s, TsMe, 6H) ppm. 13C NMR: (DMSO-d6,
126 MHz) d 163.4 (NHCO), 143.7 (Ts0), 138.5 (d0), 135.1 (Ts0),
134.9 (f0), 129.7 (Ts), 129.5 (f), 129.2 (a0), 129.1 (c), 128.9 (g),
128.4 (a), 127.4 (Ts/e), 124.5 (b), 122.1 (d), 57.7 (i), 53.7 (h), 20.9
(TsMe) ppm. MS (ESI-TOF): m/z 765.31 [M + Na]+. Anal. Calcd. for
C38H38N4O8S2ꢁC4H8O2: C, 60.71; H, 5.58; N, 6.74; S, 7.72. Found:
C, 60.33; H, 5.25; N, 7.04.
3. Results and discussion
Ligand 2 was prepared by the reaction of an aromatic amine 1
with isophthaloyl dichloride in the presence of triethylamine in
THF at ꢀ70 °C with 83% yield (Scheme 1) [5]. The next step required
selective tosylation of the hydroxyl groups of ligand 2 with p-tolu-
enesulfonyl chloride in the presence of a base. Not surprisingly, the
Table 1
Summary of crystal data and structure refinement details for 3a.
Composition
Formula weight
C38H38N4O8S2
742.84
Crystal system
Space group
a/Å
b/Å
Monoclinic
C2/c (No. 15)
30.5116(1)
6.6999(1)
21.7345(1)
130.3490(1)
3386.13(5)
4
1.457
1.950
1560
0.30 ꢂ 0.05 ꢂ 0.05
3.80 to 66.84
5471
2923 [R(int) = 0.0393]
0, 243
2.3.2. Compound 3b
White solid. mp. 175–180 °C. 1H NMR: (DMSO-d6, 500 MHz) d
9.73 (s, NHCO, 2H), 8.60 (s, e, 1H), 8.20 (d, J = 7.73 Hz, f, 2H), 7.74
(d, J = 8.28 Hz, ArTs, 4H), 7.70 (t, J = 7.58 Hz, g, 1H), 7.35 (d,
J = 8.21 Hz, ArTs, 4H), 7.18 (d, J = 7.76 Hz, d, 2H), 7.06 (td, J = 7.08
and J = 1.34 Hz, b, 2H), 6.68–6.63 (m, c/a, 4H), 4.11 (t, J = 5.71 Hz,
i, 4H), 3.39 (t, J = 5.70 Hz, h, 4H), 2.36 (s, TsMe, 6H) ppm. 13C
NMR: (DMSO-d6, 126 MHz) d 165.2 (NHCO), 144.8 (Ts0), 142.7
(a0), 134.6 (f0), 132.0 (Ts0), 130.5 (f), 130.0 (Ts), 128.2 (g), 127.5
(Ts), 127.4 (e), 127.3 (d), 127.0 (b), 123.6 (d0), 116.3 (c), 110.9 (a),
68.7 (i), 41.5 (h), 21.0 (TsMe) ppm. MS (ESI-TOF): m/z 743.29
[M + H]+. Anal. Calcd. for C38H38N4O8S2: C, 61.44; H, 5.16; N,
7.54; S, 8.63. Found: C, 61.47; H, 5.16; N, 7.68.
c/Å
b/°
V/Å3
Z
Dc/Mg mꢀ3
l
(CuK )/mmꢀ1
a
F(0 0 0)
Crystal size/mm
Theta range for data collection/°
Reflections collected
Independent reflections
Restraints/parameters
GOF on F2
1.059
R1 and R2 [I > 2
r
(I)]
0.0397, 0.0975
0.0531, 0.1051
0.276 and ꢀ0.380
2.3.3. Compound 3c
R1 and R2 (all data)
Transparent viscous oil. 1H NMR: (DMSO-d6, 500 MHz) d 9.95 (s,
NHCO, 1H), 9.77 (s, NHCO, 1H), 8.58 (s, e, 1H), 8.30 (dd, J = 6.90 and
Largest difference peak and hole/e Åꢀ3

K. Salorinne et al. / Journal of Molecular Structure 938 (2009) 137–141
139
g
f
f'
NH
NH
B
O
O
O
O
d
A
a
e
NH2
NH
d'
HN
HN
base, TsCl
THF, -70oC
NH
NR
HN
RN
c
Isophthaloyl dichloride
Et3N, THF, -70oC
A
b
a'
h
i
OH
OH
OH
OR'
OR'
1
2
3 a R = Ts, R' = H
b
R = H, R' = Ts
c R, R' = Ts/H
Scheme 1. Synthesis and tosylation of 2 with letters indicating the NMR resonance assignments.
Table 2
reaction with triethylamine as the base in THF at room temperature
gavemixturesof products, in whichboththe amineand thehydroxyl
groups were tosylated. Also, all attempts to selectively protect the
amine groups with Boc or acetyl functionality before the tosylation
reaction proved tedious and unsuccessful. However, it was found
that when the base was allowed to react with ligand 2 first at low
temperatures, deprotonation of the hydroxyl or the amine group
could be affected depending on the base used.
Bistosylated products 3a–c formed (%) in the tosylation reaction of 2 with various
bases in THF.
Base
3a
3b
3c
Triethylamine
Dabco
25
-
–
–
–
–
–
18
22
–
17
31
–
1-Methylimidazole
DMAPa
Pyridinea
–
–
Our rationale was that the stronger the base strength in THF the
more selectively the hydroxyl group would be deprotonated mak-
ing it a stronger nucleophile than the amine group. We used ion
pair basicities as a reference for the base strengths, which had been
reported in the literature for the most common amines used as
bases in THF [12]. Four different bases were selected, which are
listed here by the increasing base strength in THF: triethyl-
amine < 1-methylimidazole 6 Dabco < DMAP (Scheme 2). In addi-
tion, pyridine was also tested as it is one of the commonly used
bases in tosylation reactions.
As there are two hydroxyl and two amine groups in ligand 2, the
amount of base used was set to 2.2 equivalence in order to main-
tain the functional group selectivity in the deprotonation step.
The base was allowed to react with ligand 2 for 15 min at ꢀ70 °C
before introducing p-toluenesulfonyl chloride in the reaction. The
reaction mixture was then allowed to warm to room temperature
and stirred for two days to complete the reaction. The tosylated
products were separated by Flash chromatography and identified
as monotosylated or bistosylated products by mass spectroscopy.
When pyridine and DMAP were used as the bases only monotosy-
lated products were obtained, whereas, the reactions with triethyl-
amine, 1-methylimidazole and Dabco gave bistosylated species as
the main product with yields ranging from 17% to 31% (Table 2).
The structures of the bistosylated products 3a–c were charac-
terized by means of NMR and mass spectroscopy and X-ray crystal-
lography. ESI mass spectroscopic analysis revealed the degree of
a
Only monotosylated products were observed.
tosylation in each of the obtained products. However, the mass
spectra did not shed any information about the location of the tosyl
groups within ligand 2. The 1H NMR spectra of 3a–c showed three
distinctively different compounds but were too complicated alone
to reason which of the functional groups had been tosylated in the
reaction. Fortunately, single crystals suitable for X-ray structure
analysis were obtained by slow evaporation from DMF solution
of 3a, from which it is was evident that in 3a both of the amine
groups had been tosylated and the hydroxyl groups had remained
untouched (Fig. 1).
3a crystallizes in a monoclinic C2/c space group with only half
of the molecule in the asymmetric unit, and a two fold rotation axis
passing through the central aromatic unit (B). Two intramolecular
hydrogen bonds between the proximal amide and hydroxyl groups
(NHꢁ ꢁ ꢁO) fold the ligand in an S-shape, in which the tosyl groups
face the central aromatic ring (B) from both sides while forming
intramolecular
p
ꢁ ꢁ ꢁ
p interactions (Figs. 1 and 2b, Table 3). In addi-
tion, as a result of the intramolecular hydrogen bonds an eight
membered ring (–N11–H4ꢁ ꢁ ꢁO1–C2–C3–N4–C5–C10–) is formed
that restrains the free rotation of the h and i protons and rigidifies
the conformation, which in part explains the two separate signals
for both the h and i protons of 3a in the 1H NMR spectra (Fig. 3).
The amide carbonyl groups are in a syn orientation to one
another, andintermolecular hydrogenbonds, whichareformedwith
the hydroxyl groups (OHꢁ ꢁ ꢁO) of the neighboring molecules, arrange
the ligands into layers as shown in Fig. 2a. The layers stack via the
intermolecular
groups of the neighboring ligands, and a closer look at the structure
reveals the alternating intra- and intermolecular -stacking interac-
p
ꢁ ꢁ ꢁ
p interactions that form between the tosyl
N
N
p
Triethylamine
N
(2.11)
tions that prevail throughout the crystal packing (Fig. 2b, Table 3).
1H and 13C NMR spectroscopies were used to determine the
structures of 3b and 3c by comparing them to the spectra of 2
and 3a. Complete 1H and 13C NMR assignments for the chemical
shifts of 2 and 3a were made by using 15N, COSY, HMQC and HMBC
NMR techniques. In addition, the amide hydrogens showed a reso-
nance peak at 9.5–10.0 ppm in the 1H NMR spectra of all the com-
pounds 3a–c, so its conversion in the reaction could be ruled out.
N
N
Dabco
N
N
(0.80)
DMAP
(0.61)
1-Methylimidazole
(~1)
Scheme 2. Selected bases and their ion pair basicities in THF [12].

140
K. Salorinne et al. / Journal of Molecular Structure 938 (2009) 137–141
Fig. 1. Ortep plot (50% probability) and CPK model of the crystal structure of 3a. Intramolecular hydrogen bonds are shown as the dotted lines.
Fig. 2. Crystal packing of ligand 3a showing (a) the intra- and intermolecular hydrogen bonds (top view) and (b) the p-stacking interactions between the aromatic units (side
view).
Table 3
Selected intra- and intermolecular interactions of structure 3a.
H-bonds
Distance (Å)
p
ꢁ ꢁ ꢁ
p
(intra)
Distance (Å)
p
ꢁ ꢁ ꢁ
p
(inter)
Distance (Å)
N11ꢁ ꢁ ꢁO1 (intra)
O1ꢁ ꢁ ꢁO13 (inter)
2.888
2.845
C24ꢁ ꢁ ꢁC17
C24ꢁ ꢁ ꢁC14
C25ꢁ ꢁ ꢁC14
C25ꢁ ꢁ ꢁC15
3.469
3.589
3.734
3.893
C22ꢁ ꢁ ꢁC25
C23ꢁ ꢁ ꢁC26
C24ꢁ ꢁ ꢁC21
3.868
3.892
3.901
The comparison between ligand 2 and its bistosylated deriva-
tives 3a–c was best accomplished by using their 13C NMR spectra
since there were less overlapping signals. Also, the aromatic car-
bons, to which amine and amide groups were bonded along with
the amide carbon, were represented in the spectra. In compound
3a, in which both of the amine groups had been tosylated, the
chemical shifts belonging to the aromatic carbons of the A unit
had been drastically changed, as expected. Signals of carbons a0,
b and d had shifted upfield, where as the carbons a, c and d0 had
shifted downfield upon tosylation of the amine groups. The chem-
ical shifts of the aromatic carbons of unit B, on the other hand, had
barely been affected (Table 4). In comparison, for the compound 3b
there were no significant changes in the chemical shifts of the aro-
matic carbons of either unit A or B, but the ethylene carbons i and
h, on the other hand, were shifted considerably downfield and up-
field, respectively. This suggests that the hydroxyl groups of ligand
2 had been tosylated instead of the amine groups to give the
bistosylated product 3b. This implication was further confirmed
after looking at the spectrum of 3c, which was an almost perfect
overlap of both the spectra of 3a and 3b, which would lead to
the conclusion that in 3c one hydroxyl group and one amine group
had been tosylated or as to say that half of the molecule corre-
sponds to 3a and the other half to 3b. The same overlap was also
apparent in the 1H NMR spectrum of 3c (Fig. 3). Furthermore, in
the 1H NMR spectrum of 3c, there were two distinct signals for
the methyl protons of the tosyl group, which implies the displace-
ment of the tosyl groups in two different environments.
As it appears, the choice of a base used in the tosylation reaction
has a key role in creating selectivity between the hydroxyl and
amine functionalities, when the reaction is performed at low tem-
peratures. When triethylamine was used as the base in THF, the
amine groups of ligand 2 were tosylated selectively yielding 3a
as the only bistosylated product. With the stronger bases Dabco
and 1-methylimidazole, on the other hand, majority of the
tosylation took place at the hydroxyl functionality yielding two
bistosylated products: 3b with both hydroxyl groups and 3c with
one hydroxyl and one amine group tosylated. The explanation for
this selectivity comes from the different properties of the amine
and hydroxyl groups as nucleophiles: N-tosylation is favored by
the weaker bases as the amine group is a better nucleophile com-
pared to the hydroxyl group, however, in the presence of a stronger
base the hydroxyl group becomes deprotonated, which makes it a

K. Salorinne et al. / Journal of Molecular Structure 938 (2009) 137–141
141
*
Fig. 3. 1H NMR spectra of 3a–c in DMSO-d6 showing the chemical shift assignments for the aromatic and –CH2CH2– protons. The chemical shifts marked with 0 and in the
spectra of 3c correspond to the chemical shifts observed for 3a and 3b, respectively. (See 13C NMR spectra in the Supporting Information).
Table 4
Appendix A. Supplementary data
Selected 13C NMR shifts (ppm) of 2, 3a and 3b in DMSO-d6.
13C NMR spectra are provided for compounds 2 and 3a–c. Sup-
Carbon
2
3a
3b
plementary data associated with this article can be found, in the
online version, at doi:10.1016/j.molstruc.2009.09.015.
a0
a
b
c
d
d0
e
f
f0
g
h
143.7
111.1
127.1
115.7
127.2
123.3
127.3
130.5
134.7
128.3
45.6
129.2
128.4
124.5
129.1
122.1
138.5
127.4
129.5
134.9
128.9
53.7
142.7
110.9
127.0
116.3
127.3
123.6
127.4
130.5
134.6
128.2
41.5
References
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399;
(b) M.B. Smith, Organic Synthesis, McGraw-Hill, New York, 1994, pp. 137–138
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i
59.5
57.7
68.7
NHCO
165.2
163.4
165.2
(c) R.J. Cremlyn, An Introduction to Organosulfur Chemistry, Wiley, West
Sussex, 1996, pp. 103–110.
[2] Sulfonamides as such are used as pharmaceuticals and pesticides, see: R.J.
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better nucleophile and O-tosylation is therefore favored. Under
these conditions, with the heterocyclic bases pyridine and DMAP,
only monotosylated products were formed, which were estab-
lished by mass spectroscopy but could not be fully characterized.
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7291;
4. Conclusions
In conclusion, a synthetic strategy for the O- and N-tosylation of
N,N-bis(2-aminophenyl)isophthalamide based ligands has been
described. Selectivity between hydroxyl and amine functionalities
was obtained by the appropriate choice of the base, which was
chosen according to the base strength, while performing the tosy-
lation reaction at low temperatures. NMR and mass spectroscopic,
and X-ray crystallographic analyses were used to establish the
structures of the obtained bistosylated products.
(f) K. Keisuke, Chem. Ind. (London, U.K.) 1 (1974) 345 (and references therein).
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Acknowledgements
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We are grateful to Mr. Reijo Kauppinen for his help with the
NMR experiments. Financial support from the Academy of Finland
(project 116503) is appreciated.