Janus head type lone pair-π-lone pair and S?F?S interactions in retaining hexafluorobenzene

Article abstract of DOI:10.1039/c6ce00496b

A series of eight tris-arylthiotriazines were synthesized to study the lone pair-π interaction between the triazine ring centroid of these molecules and halogenated solvents. All the eight compounds were characterized using ¹H and ¹³C NMR spectroscopy and single crystal X-ray diffraction techniques. All these compounds show interesting structural properties in the solid state. Unprecedented Janus head type lp?π?lp and S?F?S interactions were observed between one of the tris-arylthiotriazines and hexafluorobenzene.

Full text of DOI:10.1039/c6ce00496b

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Janus head type lone pair–π–lone pair and S⋯F⋯S
interactions in retaining hexafluorobenzene†
Cite this: DOI: 10.1039/c6ce00496b
*
Sonam Mehrotra and Raja Angamuthu
Received 3rd March 2016,
Accepted 13th April 2016
A series of eight tris-arylthiotriazines were synthesized to study the lone pair–π interaction between the tri-
azine ring centroid of these molecules and halogenated solvents. All the eight compounds were character-
ized using 1H and 13C NMR spectroscopy and single crystal X-ray diffraction techniques. All these com-
pounds show interesting structural properties in the solid state. Unprecedented Janus head type lp⋯π⋯lp
and S⋯F⋯S interactions were observed between one of the tris-arylthiotriazines and hexafluorobenzene.
DOI: 10.1039/c6ce00496b
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wished to take advantage of the well-known “Piedfort Diad” for-
mation (Chart 1).17–23 According to literature reports17,18 sym-
1. Introduction
It is apparent from the recent literature that lone pair-π (lp⋯π)
interactions are weak yet important for the stabilization of three-
dimensional structures of biomolecules1 in addition to other
well-established weak interactions such as hydrogen bonding,
anion–π interactions, and cation–π interactions. Some experi-
mental evidence has been reported very recently to establish the
applications of anion–π interactions2–6 and cation–π
interactions7–10 while the lp⋯π interactions are yet to be proved
useful in small molecular systems. To the best of our knowledge,
all the reported synthetic molecular systems that exhibit lp⋯π
interactions were discovered serendipitously. We hypothesised
to devise molecular systems that will have lone pair–π interactions
with small molecules of environmental and industrial interest
(CFCs, CO2, SO2) as these interactions may be strong enough to
sequester the small molecules and weak enough to release them
with minimal energy input such as slight elevation of tempera-
ture and/or depression in pressure. This prompted us to investi-
gate host molecules comprising electron deficient ring systems
in order to demonstrate the functional relevance of lp⋯π inter-
actions. With this motivation, we have synthesized a number of
tris-arylthiotriazine molecules (TArTTz), as the valley of electron
deficiency present at the centre of the C3N3 ring of these
molecules6,11–13 is known to attract lone pairs of electronegative
atoms of neighbouring molecules.14–16 We have anticipated that
this will allow us to park small molecules in between C3N3 rings
of adjacent molecules through lp⋯π interactions. For this, we
triaryloxytriazines (TArOTz) have an interesting structural fea-
ture of peripheral aryl rings oriented almost perpendicular to the
central C3N3 ring and form stacked diads known as Piedfort
units21 which eventually are the synthons for higher level supra-
molecular assemblies.17–19
One of the inherent disadvantages of the known ‘Piedfort
Diads’ is that the distance DTz···Tz between the C3N3 rings are in
the range of 3 and 4 Å whereas to park a small molecule in be-
tween two sym-triaryloxytriazines through lp⋯π interaction(s), a
minimum of ∼8 Å distance might be required.17–19 To achieve
this we have intended to utilize arylthio substitutions instead of
aryloxy units where the aryl rings comprise varying substitutions
in order to tune the distance between adjacent C3N3 rings and
the type of interactions between neighbouring molecules.
Laboratory of Inorganic Synthesis and Bioinspired Catalysis (LISBIC), Department
of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, India.
E-mail: Raja@iitk.ac.in
† Electronic supplementary information (ESI) available: NMR spectra of all the
compounds. X-ray crystallographic data in CIF format have been deposited with
the Cambridge Structural Database. CCDC 1403546–1403550 (1–5), 1436791–
1436793 (6·0.5C6F6, 6, 7) and 1452878 (8) contain the supplementary crystallo-
graphic data for this paper. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c6ce00496b
Chart 1 Piedfort units of tris-aryloxotriazines (TArOTz) with 3-fold
symmetry (C3IJg), C3i, and D3)17–21,23–25 and the motif anticipated and
observed in the present work for tris-arylthiotriazines (TArTTz).
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Herein we report eight sym-triazine based molecules that
2.2. NMR spectroscopy
are decorated with aryl rings possessing 4-methyl (2), 4-chloro
(3), 3-nitro (4), 2-methyl-5-nitro (5), 2,6-dimethyl (6), penta-
methyl (7) and 2,3,5,6-tetrafluoro (8) substitutions (Scheme 1).
The NMR spectra of all the eight TArTTz compounds indicate
that these molecules are C3 symmetric in solution at room
temperature in NMR time scale though it is not the case in
the solid state as seen in the SCXRD structures of these
1
All the eight compounds were characterized using H and 13C
NMR spectroscopy. The solid state structures of all the mole-
cules were studied by employing single crystal X-ray diffraction
(SCXRD) and were found to comprise a number of inter and
intramolecular interactions such as π⋯π and lp⋯π including
Janus head type lp⋯π⋯lp and S⋯F⋯S interactions.
1
TArTTz compounds. As H NMR spectroscopy does not differ-
entiate the mono and disubstituted triazines from TArTTz,
13C NMR spectroscopy was used as the finite preliminary
analysis where all the TArTTz exhibit a signal around 180
ppm indicating the presence of three similar tertiary carbons
in the triazine ring system.
2. Results and discussion
2.1. Syntheses of tris-arylthiotriazines 1–8
2.3. Description of the structures
An equivalent of cyanuric chloride was reacted with three
equivalents of thiophenol, 4-methylthiophenol, 4-chloro-
thiophenol, 3-nitrobenzenethiol, 2-methyl-5-nitrobenzenethiol,
2,6-dimethylthiophenol, 2,3,4,5,6-pentamethylthiophenol and
2,3,5,6-tetrafluorothiophenol in the presence of a suitable base
to obtain 2,4,6-trisIJphenylthio)-1,3,5-triazine (1), 2,4,6-trisIJp-
tolylthio)-1,3,5-triazine (2),26 2,4,6-trisIJ(4-chlorophenyl)thio)-
1,3,5-triazine (3), 2,4,6-trisIJ(3-nitrophenyl)thio)-1,3,5-triazine
(4), 2,4,6-trisIJ(2-methyl-5-nitrophenyl)thio)-1,3,5-triazine (5),
2,4,6-trisIJ2,6-dimethylphenylthio)-1,3,5-triazine (6), 2,4,6-tris-
IJ2,6-dimethylphenylthio)-1,3,5-triazine (7) and 2,4,6-tris-
IJ(2,3,5,6-tetrafluorophenyl)thio)-1,3,5-triazine (8), respectively
(Scheme 1). All the eight compounds were characterized using
1H and 13C NMR spectroscopy and the single-crystal X-ray dif-
fraction technique. The thermal stability of these molecules was
studied by thermogravimetric analysis.
Single crystals of TArTTz 1–8 suitable for SCXRD studies were
grown by slow evaporation or diffusion methods as reported
in the experimental section in detail. Unfortunately, none of
the TArTTz molecules crystallised in any of the three required
symmetries (C3IJg), C3i or D3),17–19 which would have allowed
the formation of the anticipated Piedfort units. To the best of
our knowledge, many known free tris-aryloxotriazines form
Piedfort units in their solid states.17–23 However, TArOTz are
also known to attain lower symmetry when they are coordi-
nated to metal ions.27 One possible reason for the lowering of
symmetry on going from TArOTz to TArTTz could be the possi-
bility of intramolecular π⋯π interaction in TArTTZ molecules
owing to the bigger size of sulphur. All the TArTTz molecules
exhibit weak intramolecular π⋯π interactions of distances be-
tween 3.94 and 4.38 Å, which were not retained in solution at
room temperature as observed from their NMR spectra.
The TArTTz 1, where the phenyl rings do not have any sub-
stitution, possesses an intermolecular lone pair⋯π interaction
between the lone pair of thioether sulphur and the triazine
ring (SIJlp)⋯π) with a distance (DSIJlp)⋯π) of 3.207 Å which is
shorter than the sum of van der Waals radii (C + S = 3.5 Å; N +
S = 3.35 Å).13 The S3 A⋯ring distances are 3.471 Å (S3
A⋯N1B), 3.472 Å (S3 A⋯N2B), 3.527 Å (S3 A⋯N3B), 3.391 Å
(S3 A⋯C1B), 3.453 Å (S3 A⋯C2B), and 3.525 Å (S3 A⋯C3B).
This may be the first observed S(lp)⋯π involving a 1,3,5-
triazine ring system whereas few other known S(lp)⋯π involve
1,2,3-triazine and 1,3,4-triazine rings (Fig. 1).13 The 4-methyl
substituted TArTTz 2 does not have any significant lp⋯π inter-
actions whereas the 4-chloro substituted TArTTz 3 exhibits an
intermolecular Cl(lp)⋯π interaction (DClIJlp)⋯π = 3.542 Å). The
sums of the van der Waals radii are 3.45 Å (C + Cl) and 3.30 Å
(N + Cl);13 the Cl2⋯ring distances are 3.648 Å (Cl2⋯N1),
4.181 Å (Cl2⋯N2), 3.550 Å (Cl2⋯N3), 3.981 Å (Cl2⋯C1),
3.931 Å (Cl2⋯C2), and 3.353 Å (Cl2⋯C3). According to
Mooibroek et al., the observed mean DClIJlp)⋯π is 3.346 Å.12
Hence, the Cl(lp)⋯π interaction observed in TArTTz 3 may be
considered as a weak one.
The 3-nitro substituted TArTTz 4 has all three nitro groups fac-
ing the same side of the triazine ring while the 2-methyl-5-nitro
substituted TArTTz 5 has two nitro groups in one side and the
other one facing the opposite side of the triazine ring. This indi-
cates that the 2-methyl-5-nitrophenyl rings have free rotation
Scheme
1 Tris-1,3,5-arylthiotriazines (TArTTz) synthesised for the
present study and the schematic diagram of the observed synergism of
fluorine bonding and lone pair–π interactions.
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The SCXRD structure of TArTTz 8 (Fig. 3) presents an inter-
esting dimeric motif exhibiting many intermolecular interac-
tions such as S⋯F fluorine bonds (S3⋯F8, 2.991 Å; S1···F1,
3.251 Å; S2⋯F2, 3.498 Å), an intermolecular FIJlp)···π interaction
(DFIJlp)⋯π = 2.967 Å) and an intramolecular π⋯π interaction
(DCg⋯Cg = 3.944 Å). The F(lp)⋯π interaction observed in
TArTTz 8 is a strong one as the DFIJlp)⋯π of 2.967 Å is well below
the sums of the van der Waals radii (C + F = 3.17 Å; N + F =
3.02 Å).13 The F4···ring distances are 3.273 Å (F4⋯N1), 3.111 Å
(F4⋯N2), 3.414 Å (F4⋯N3), 3.404 Å (F4⋯C1), 3.077 Å
(F4⋯C2), and 3.212 Å (F4⋯C3) which are not too far from
the sum of the van der Waals radii.
As we have observed the intermolecular lp⋯π interactions in
TArTTz 1, 3 and 8, we set out to investigate the interactions with
fluorinated molecules as solvents. The halogenated aromatic
molecules, especially C6F6, are known to be involved in lp⋯π in-
teractions as they can participate through the halogen lone pair
and through the electron deficient centre of the aromatic ring.
We have observed a peculiar crystal structure where the C6F6
molecule involves in Janus head type of lp⋯π⋯lp interaction
on both sides of the ring (DNIJlp)⋯π = 3.51 Å) where the nitrogen
lone pairs of two TArTTz 6 molecules interact with the ring cen-
tre of C6F6 (Fig. 4). Furthermore, the fluorine atoms at the
1,4-positions of the C6F6 ring also take part in fluorine
bonding28–31 with the thioether sulphur atoms of the TArTTz 6
molecules with interesting S⋯F⋯S motifs (DS⋯F = 3.365 and
3.442 Å). Apart from the lp⋯π⋯lp and S⋯F⋯S interactions,
the structure of 6·0.5C6F6 possesses extensive inter and intramo-
lecular π⋯π stacking networks.
Fig. 1 X-ray structures of 2,4,6-trisIJphenylthio)-1,3,5-triazine (1), 2,4,6-
trisIJp-tolylthio)-1,3,5-triazine (2), and 2,4,6-trisIJ(4-chlorophenyl)thio)-1,3,5-
triazine (3). The hydrogen atoms are not shown for clarity. Intramolecular
π⋯π interactions: (1) 4.287 and 4.350; (2) 4.384; (3) 4.158 Å.
in solution as TArTTz 5 has C3 symmetry in solution. Apart
from the intramolecular π⋯π interactions, TArTTz 4 has an
interesting intermolecular π⋯π interaction (DCg⋯Cg = 3.616
Å) between the triazine ring of one molecule with the
3-nitrophenyl ring of another molecule. The TArTTz 5 pos-
sesses an intermolecular π⋯π interaction (DCg⋯Cg = 3.652 Å),
which presents a ladder of four aryl rings (Fig. 2). The TArTTz
6 and 7 also present the same ladder-type structure of four
dimethylphenyl rings and four pentamethylphenyl rings with
intermolecular (DCg⋯Cg = 3.868 Å in 6; 3.913 Å in 7) and intra-
molecular π⋯π stacking (DCg⋯Cg = 3.965 Å in 6; 4.114 Å in 7).
2.4. Thermal stability of TArTTz molecules
The thermal stability of TArTTz compounds 1–8 was studied
by means of thermogravimetric analysis. Compounds 1–3, 6
and 7 were found to be stable until ∼280 °C, 4 was stable until
∼260 °C, whereas compounds 5 and 8 began to decompose at
∼230 °C. Interestingly, adduct compound 6·0.5C6F6 lost the
hexafluorobenzene molecule at 140 °C (Fig. 5) which is 60 °C
above the boiling point of C6F6 which indicates the synergism
of the lp⋯π⋯lp and S⋯F⋯S interactions in retaining the
C6F6 molecule in the lattice.
Fig. 2 X-ray structures of 2,4,6-trisIJ(3-nitrophenyl)thio)-1,3,5-triazine (4),
2,4,6-trisIJ(2-methyl-5-nitrophenyl)thio)-1,3,5-triazine
(5),
2,4,6-trisIJ2,6-
dimethylphenylthio)-1,3,5-triazine (6), and 2,4,6-trisIJ2,6-dimethylphenylthio)-
1,3,5-triazine (7). The hydrogen atoms are not shown for clarity.
Intramolecular π⋯π interactions: (4), 4.041; (5), 4.048; (6), 3.965; (7), 4.114 Å.
Intermolecular π⋯π interactions: (4), 3.616; (5), 3.652 (6); 3.868; (7), 3.913 Å.
Fig.
3 X-ray structure of 2,4,6-trisIJ(2,3,5,6-tetrafluorophenyl)thio)-
1,3,5-triazine (8). Intramolecular π⋯π interaction distance: 3.944 Å.
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Fig. 5 The thermogravimetric diagram of 6·0.5C6F6 showing the loss
of the C6F6 solvate at 140 °C and the decomposition of 6 at 280 °C.
(Avra), 2,6-dimethylthiophenol (Alfa Aesar), 2,3,4,5,6-
pentamethylbenzene-1-sulfonylchloride (Alfa Aesar) and 2,3,5,6-
tetrafluorothiophenol (Alfa Aesar) were used as received from
commercial sources. Solvents were distilled under dry nitrogen at-
mosphere using conventional methods. Heavy-walled high-
pressure round bottom flasks were acquired from Ace Glass Inc.
4.2. Methods
Elemental analyses were carried out on a Perkin-Elmer
CHNS/O analyser. The NMR spectra were recorded on JEOL
500 MHz and JEOL 400 MHz spectrometers. The temperature
was kept constant using a variable temperature unit within
the error limit of 1 K. The software MestReNova was used
for the processing of the NMR spectra.32 Tetramethylsilane
(TMS) or the deuterated solvent residual peaks were used for
calibration. Mass spectrometry experiments were performed
on a Waters-Q-ToF-Premier-HAB213 equipped with an electro-
spray interface. The spectra were collected by constant infu-
sion of the sample dissolved in methanol or acetonitrile with
0.1% formic acid. Thermogravimetric analyses were carried
out in dry nitrogen atmosphere at a heating rate of 10 °C
min−1 on a Mettler Toledo TGA/DSC1 Stare System.
Fig.
4 X-ray structure of 2,4,6-trisIJ2,6-dimethylphenylthio)-1,3,5-
triazine (6) crystallized in hexafluorobenzene (6·0.5C6F6). The
hydrogen atoms are not shown for clarity. The packing diagram of 6
·0.5C6F6 shows the presence of extensive inter and intramolecular
π⋯π stacking. Pink coloured dimethylphenyl rings are involved in both
inter and intramolecular stacking and the purple coloured rings are
involved in the intermolecular stacking. π⋯π interactions: 4.100 Å
(intra, pink); 4.160 Å (inter, pink); 4.280 Å (inter, purple).
3. Conclusions
The tris-arylthiotriazines reported herein show that the lone
pair–π interactions can indeed be engineered by design and be
used for applications such as capturing or retaining small mole-
cules which posses at least one lone pair (halocarbons, CO2, or
SO2). The observed feature of the synergistic Janus head
lp⋯π⋯lp and S⋯F⋯S motif is interesting in the context of
fluorine bonding and warrants further experimental and com-
putational studies as the fluorine bonding is a unique and
emerging section of weak interactions which might be relevant
to pharmacologically important fluorinated drug molecules.29
Warning: Reactions using heavy-walled high-pressure round
bottom flask with screw cap must be carried cautiously. The
danger of explosion can be avoided by performing the reactions
in smaller scales. The scales presented here are safe with a 250
ml heavy-walled high-pressure round bottom flask.
4.3. Synthetic procedures
4.3.1. Synthesis of 2,4,6-trisIJphenylthio)-1,3,5-triazine (1).
Thiophenol (3.3 g, 30 mmol) was added to a solution of
cyanuric chloride (1.8 g, 10 mmol) in 80 ml acetone. The
resulting solution was treated with an aqueous NaOH solu-
tion (1.2 g, 30 mmol in 40 ml H2O) dropwise at 0 °C with
continuous stirring for 1 h. Then the reaction mixture was
stirred for 4 h at 35 °C. The resulting white precipitate was
collected through filtration and washed with cold water
4. Experimental
4.1. Materials
Cyanuric chloride (Avra Synthesis), thiophenol (SDFCL),
4-methylthiophenol (Avra Synthesis), 4-chlorothiophenol (Avra
Synthesis), nitrobenzene (Merck), chlorosulfonic acid (Spectro-
chem), triphenylphosphine (Avra synthesis), 4-nitrotoluene
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(10 ml), followed by cold ethanol (2 ml) and dried under high
vacuum (3.4 g, 87%). X-ray quality crystals were grown by the
slow evaporation of ethanol solution. 1H NMR (500 MHz,
CDCl3): δ 7.36 (t, J = 6.9, 6H), 7.32 (t, J = 8.0, 6H), 7.23 (t, J =
8.0, 3H); 13C NMR (500 MHz, CDCl3): δ 180.43, 134.59, 129.22,
128.95, 127.17. Anal. calcd (%) for (C21H15N3S3·0.2CH3CH2OH):
C 61.97, H 3.94, N 10.13; found: C 61.86, H 3.61, N 10.62.
4.3.2. Synthesis of 2,4,6-trisIJp-tolylthio)-1,3,5-triazine (2).
This compound has been reported in the literature and it
was synthesised by the reaction of 1,3,5-triazine-2,4,6-trithiol
with 4-bromotoluene catalysed by palladium nanoparticles.33
4-methylthiophenol (3.7 g, 30 mmol) was added to a solution
of cyanuric chloride (1.8 g, 10 mmol) in 80 ml acetone. The
resulting solution was treated with an aqueous NaOH solu-
tion (1.2 g, 30 mmol in 40 ml water) dropwise at 0 °C and
stirred for an hour at the same temperature. Then the reac-
tion mixture was stirred for 4 h at 35 °C. The resulting white
precipitate was collected through filtration and washed with
cold water (15 ml), followed by cold ethanol (2 ml) and dried
under high vacuum (3.2 g, 74%). Needle-shaped crystals were
collected through slow evaporation of methanol within two
which was purified by passing through a silica column as a so-
1
lution in chloroform (6.5 g, 56%). H NMR (500 MHz, CDCl3):
δ 8.88 (d, 1H), 8.61 (dd, 1H), 8.38 (dd, 1H), 7.90 (t, 1H); 13C
NMR (500 MHz, CDCl3): δ 148.36, 145.58, 132.20, 131.52,
129.67, 122.31.
4.3.5. Synthesis of 3-nitrobenzenethiol. Triphenylphosphine
(9.87 g, 37.63 mmol) was slowly added to a stirred solution of
3-nitrobenzene-1-sulfonyl chloride (2.78 g, 12.54 mmol) in tolu-
ene (30 ml) under nitrogen atmosphere, which resulted in a
brown solution. To this, a solution of iodine in toluene (5.3 mg,
2 ml) was added dropwise and the resulting mixture was
refluxed for 3 h. Addition of an iodine solution changed the col-
our of the reaction mixture from brown to yellow. The resulting
yellow solution was cooled to room temperature and treated
with 5 ml of water, which resulted in a turbid solution. The or-
ganic layer was extracted with 10% aqueous NaOH solution (3 ×
15 ml). The aqueous alkali layer was acidified to pH 3 with HCl
(6 N), extracted with dichloromethane (3 × 15 ml) and dried
over MgSO4. The solvent was removed and dried under high
vacuum to yield a yellow liquid (1.75 g, 89%). 1H NMR
(400 MHz, CDCl3): δ 8.09 (s, 1H), 7.96 (d, J = 7.65, 1H), 7.54 (d,
J = 7.65, 1H), 7.39 (t, J = 7.95, 1H), 3.72 (s, 1H); 13C NMR
(500 MHz, CDCl3): δ 148.23, 134.51, 133.84, 129.66, 123.29,
120.28.
4.3.6. Synthesis of 2,4,6-trisIJ(3-nitrophenyl)thio)-1,3,5-triazine
(4). A solution of 3-nitrobenzenethiol (1.75 g, 11.2 mmol) in
20 ml of acetone was added to a stirred solution of cyanuric
chloride (688 mg, 3.73 mmol) in 20 ml of acetone under nitro-
gen atmosphere. After that, NaOH (447 mg, 11.2 mmol) in water
(30 ml) was added dropwise (during the addition of aqueous
NaOH solution, a yellow precipitate was formed). This yellow re-
action mixture was stirred at 0 °C for 1 h, at room temperature
for 2 h and at 35 °C for 2 h. The resulting yellow precipitate was
collected through filtration and dried under vacuum (1.1 g,
55%). Crystals were grown by the slow diffusion of diethyl ether
into an acetonitrile solution. 1H NMR (500 MHz, DMSO-d6): δ
8.19 (m, 3H), 8.11 (dd, J = 8.2, 2.3, 3H), 7.86 (t, 3H), 7.54 (q, 1H);
13C NMR (400 MHz, DMSO-d6): δ 175.08, 147.79, 141.37, 132.45,
130.08, 129.42, 123.58. Anal. calcd (%) for (C21H12N6O6S3): C
46.66, H 2.24, N 15.55; found: C 46.64, H 2.06, N 15.49.
4.3.7. Synthesis of 2-methyl-5-nitrobenzene-1-sulfonyl
chloride. A 250 ml heavy-walled high-pressure round bottom
flask (Ace Glass, Inc.) was charged with 4-nitrotoluene (6.86 g,
50 mmol) and cold chlorosulfonic acid (8.3 ml, 125 mmol)
was added dropwise, keeping the temperature below 5 °C. The
reaction mixture was heated at 50 °C for 30 min and then
the temperature was increased by 20 °C every 30 minutes until
it reached 140 °C. Then the reaction mixture was stirred
at 140 °C for 22 h. The dark brown solution was cooled to
room temperature before opening the flask, poured onto
crushed ice (∼150 ml) with vigorous stirring for half an
hour. The brown precipitate formed was filtered and dried
under vacuum (9.5 g, 80.6%). 1H NMR (500 MHz, DMSO-d6):
δ 8.49 (d, J = 2.85, 1H), 8.05 (dd, J = 8.27, 2.30, 1H), 7.43 (d,
J = 8.60, 1H), 2.62 (s, 3H); 13C NMR (400 MHz, DMSO-d6): δ
147.55, 145.26, 144.61, 132.55, 123.78, 121.38, 20.53.
1
days. H NMR (500 MHz, CDCl3): δ 7.23 (d, J = 7.95, 6H), 7.04
(d, J = 7.95, 6H), 2.36 (s, 9H); 13C NMR (500 MHz, CDCl3): δ
180.60, 139.05, 134.92, 129.72, 123.86. Anal. calcd (%) for
(C24H21N3S3): C 64.39, H 4.73, N 9.39; found: C 64.27, H 4.61,
N 9.83.
4.3.3. Synthesis of 2,4,6-trisIJ(4-chlorophenyl)thio)-1,3,5-
triazine (3). 4-chlorothiophenol (4.33 g, 30 mmol) was added
to a solution of cyanuric chloride (1.8 g, 10 mmol) in 80 ml
acetone. The resulting solution was treated with an aqueous
NaOH solution (1.2 g, 30 mmol in 40 ml H2O) dropwise at
0 °C and stirred for an hour at the same temperature. The
resulting white precipitate was collected through filtration
and washed with cold water (10 ml), followed by cold ethanol
(2 ml) and dried under high vacuum (4.0 g, 81%). Needle-
shaped crystals were collected from a methanolic solution
1
through slow evaporation. H NMR (500 MHz, CDCl3): δ 7.27
(d, J = 9.1, 6H), 7.23 (d, J = 8.5, 6H); 13C NMR (500 MHz,
CDCl3): δ 180.29, 136.47, 136.32, 129.41, 125.38. Anal. calcd
(%) for (C21H12Cl3N3S3): C 49.56, H 2.38, N 8.26; found: C
49.63, H 2.31, N 8.13.
4.3.4. Synthesis of 3-nitrobenzene-1-sulfonyl chloride. A
250 ml heavy-walled high-pressure round bottom flask (Ace
Glass, Inc.) was charged with nitrobenzene (3 ml, 29.23 mmol)
and 5 ml of cold chlorosulfonic acid (77.22 mmol) was added
slowly at room temperature with continuous stirring; the flask
was sealed with a Teflon screw cap. The reaction mixture was
heated at 40 °C for 30 min and then the temperature was in-
creased by 20 °C every 30 minutes until it reached 140 °C.
Then the reaction mixture was stirred at 140 °C for 40 hours.
The resulting brown solution was cooled to room temperature
before opening the cap and poured onto ∼50 ml of crushed
ice, stirred for 5 minutes, extracted with CHCl3 (3 × 15 ml),
then all the organic layers were combined, dried over MgSO4
and the solvent was evaporated to obtain the crude batch of
3-nitrobenzene-1-sulfonyl chloride as a brown solid (63%)
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4.3.8.
Synthesis
of
2-methyl-5-nitrobenzenethiol.
toluene (4.5 mg) was added dropwise and refluxed for 3 h. The
resulting orange colored reaction mixture was cooled to room
temperature; then 30 ml of water was added to the mixture
and it was stirred for 10 minutes. The organic layer was sepa-
rated, dried over MgSO4 and the solvent was evaporated, then
it was dissolved in chloroform, passed through a silica plug
and the solvent was dried under vacuum to yield a white solid
Triphenylphosphine (7.86 g, 30 mmol) was slowly added to a
stirred solution of 2-methyl-5-nitrobenzene-1-sulfonyl chloride
(2.36 g, 10 mmol) in 50 ml of toluene under nitrogen atmo-
sphere and stirred for ten minutes. To this solution, iodine
in 2 ml of toluene (4.5 mg) was added dropwise and refluxed
for 3 h. After that the reaction mixture was cooled to room
temperature and 15 ml of water was added, which made the
solution turbid. The organic layer of the turbid solution was
extracted with 10% aqueous NaOH solution (3 × 15 ml). The
aqueous alkali layer was acidified to pH 3 using HCl (6 N),
extracted using dichloromethane (3 × 20 ml) and dried over
MgSO4. The solvent was removed and dried under high vac-
uum to yield a reddish yellow solid (1.08 g, 63%). 1H NMR
(400 MHz, CDCl3): δ 8.11 (d, J = 2.28, 1H), 7.88 (dd, J = 8.24,
2.28, 1H), 7.28 (d, J = 8.24, 1H), 3.57 (s, 1H), 2.40 (s, 3H); 13C
NMR (400 MHz, CDCl3): δ 146.81, 143.64, 134.16, 131.17,
124.42, 120.94, 21.56.
4.3.9. Synthesis of 2,4,6-trisIJ(2-methyl-5-nitrophenyl)thio)-
1,3,5-triazine (5). A solution of 2-methyl-5-nitrobenzenethiol
(1.08 g, 6.38 mmol) in 20 ml of acetone was added to a
stirred solution of cyanuric chloride (392 mg, 2.12 mmol) in
10 ml of acetone under nitrogen atmosphere. After that, an
aqueous solution of NaOH (255 mg, 6.38 mmol in 15 ml
H2O) was added dropwise. During the addition of aqueous
NaOH solution, a light yellow precipitate was formed. This re-
action mixture was stirred at 0 °C for 1 h and at 35 °C for
3 h. The resulting white precipitate was collected through fil-
tration, washed with water and dried under vacuum (1.0 g,
83%). Crystals were obtained through the slow evaporation of
1
(2.56 g, 69%). H NMR (400 MHz, CDCl3): δ 3.15, (1H, s), 2.41,
(6H, s), 2.27, (6H, s), 2.24, (3H, s); 13C NMR (500 MHz, CDCl3):
δ 133.11, 132.97, 132.75, 127.94, 19.41, 17.47, 17.04.
4.3.12.
Synthesis
of
2,4,6-trisIJ2,3,4,5,6-pentamethyl
phenylthio)-1,3,5-triazine (7). 2,3,4,5,6-pentamethylbenzenethiol
in 10 ml of THF (1 g, 5.54 mmol) was added to a stirred solution
of cyanuric chloride (340 mg, 1.84 mmol) in 20 ml of THF. To
this mixture, an aqueous solution of NaOH (221 mg in 15 mL
H2O) was added dropwise at 0 °C, stirred for an hour at 0 °C, for
2 h at room temperature and 2 h at 45 °C. Then the reaction
mixture was cooled to room temperature, the formed white pre-
cipitate was filtered and dried under vacuum (900 mg, 79%).
Crystals were grown by layering methanol on a saturated di-
1
chloromethane solution in one day at 4 °C. H NMR (500 MHz,
CDCl3): δ 2.26, (18 H, s), 2.22, (18H, s), 2.12, (9H, s); 13C NMR
(500 MHz, CDCl3): δ 179.80, 138.40, 136.60, 132.87, 124.20, 19.37,
17.42, 17.36. Elemental analysis calculated for C36H45N3S3: C,
70.20; H, 7.36; N, 6.82; found: C, 70.0; H, 7.51; N 6.10.
4.3.13. Synthesis of 2,4,6-trisIJ(2,3,5,6-tetrafluorophenyl)-
thio)-1,3,5-triazine (8). In a 100 ml Schlenk flask, cyanuric
chloride (500 mg, 2.71 mmol) was dissolved in 40 mL of ace-
tone under nitrogen atmosphere and stirred until it was
dissolved. 2,3,5,6-tetrafluorobenzenethiol (1.12 ml, 9.48 mmol)
was added to the solution of cyanuric chloride. Then DIPEA
(1.65 ml, 9.48 mmol) was added slowly at 0 °C and refluxed
overnight. The reaction mixture was cooled to RT and the vol-
atiles were evaporated. The yellow oily liquid obtained was
dissolved in chloroform (30 ml) and washed with distilled wa-
ter (3 × 10 ml). The organic layer was dried over MgSO4 then
concentrated to a volume of 5 ml, and diethyl ether (10 ml)
was layered to get a white precipitate (1.0 g, 62%). Crystals
were grown in a hexane solution within four days at −20 °C.
1H NMR (400 MHz, CDCl3): δ 7.24–7.15, (m, 1 H); 13C NMR
(400 MHz, CDCl3): δ 178.01, 148.28, 146.96, 145.59, 144.48.
1
the methanol–acetone mixture. H NMR (500 MHz, DMSO-d6):
δ 8.15 (s, 3H), 8.13 (d, J = 8.6, 3H), 7.46 (d, J = 8.05, 3H), 2.30 (s,
9H); 13C NMR (500 MHz, DMSO-d6): δ 178.77, 150.86, 145.57,
132.00, 130.71, 127.59, 125.42. Anal. calcd (%) for (C24H18N6O6S3):
C 49.47, H 3.11, N 14.42; found: C 49.04, H 3.22, N 13.62.
4.3.10. Synthesis of 2,4,6-trisIJ2,6-dimethylphenylthio)-
1,3,5-triazine (6). In a 250 ml round bottom flask, cyanuric
chloride (500 mg, 2.71 mmol) was dissolved in 40 ml of acetone
under nitrogen atmosphere and stirred until it was dissolved.
2,6-dimethylbenzenethiol (1.0 mL, 8.13 mmol) was added to
the acetone solution. Then DIPEA (1.40 ml, 8.13 mmol) was
added slowly at 0 °C and refluxed overnight. The reaction mix-
ture was cooled down to RT and the solvent was evaporated.
The resulting yellow oily liquid was dissolved in dichloro-
methane (10 ml) and washed with water (3 × 10 ml). The
organic layer was dried over MgSO4 and the solvent was evapo-
rated to obtain a white solid (730 mg, 73%). 1H NMR (400 MHz,
CDCl3): δ 7.08, (3H, t), 6.92, (6H, d), 2.25, (18 H, s); 13C NMR
(400 MHz, CDCl3): δ 179.48, 143.33, 130.0, 128.15, 126.25, 21.76.
Elemental analysis calculated for C27H27N3S3·0.8CH3COCH3: C,
65.86; H, 5.98; N, 7.84; found: C, 65.54; H, 5.54; N, 7.83.
4.4. X-ray crystallography
Single-crystal X-ray data were collected on a Bruker SMART
APEX CCD diffractometer using graphite-monochromated Mo
Kα radiation (λ = 0.71069 Å). The linear absorption coeffi-
cients, the scattering factors for the atoms, and the anoma-
lous dispersion corrections were taken from International Ta-
bles for X-ray Crystallography. Data integration and
reduction were conducted with SAINT. An empirical absorp-
tion correction was applied to the collected reflections with
SADABS using XPREP. The structures were determined by di-
rect methods using SHELXTL and refined on F2 by a full-
matrix least-squares technique using the SHELXL-97 program
package. The lattice parameters and structural data are listed
at the end of the ESI.
4.3.11. Synthesis of 2,3,4,5,6-pentamethylbenzenethiol.
2,3,4,5,6-pentamethylbenzene-1-sulfonyl chloride (5.0 g,
20.26 mmol) was dissolved in 80 mL of dry toluene under N2
atmosphere. Triphenylphosphine (15.94 g, 60.79 mmol) was
added portionwise into it. To this solution, iodine in 2 ml of
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This work was supported by the Ministry of Earth Sciences, India
and generous funding from the Indian Institute of Technology
Kanpur (IITK, India) through the “New Faculty Initiation Grant”
(IITK/CHM/20120078). SM acknowledges the University Grants
Commission (UGC, India) for the Senior Research Fellowship.
RA acknowledges Dr. Tiddo J. Mooibroek for inspiration. This
paper is dedicated to Professor Ray J. Butcher on the occasion of
his 70th birthday.
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