Hindered C–N bond rotation in triazinyl dithiocarbamates

Article abstract of DOI:10.1016/j.molstruc.2017.09.063

The substituent and solvent effects on the rotation around a C–N amide bond were studied for a series of triazine dibenzylcarbamodithioates. The Gibbs free energies (ΔG^?) were measured to be 16–18 kcal/mol in DMSO-d₆ and toluene-d₈ using variable-temperature nuclear magnetic resonance (VT-¹H NMR) spectroscopy. Density functional theory (DFT) calculations reproduced the experimental observations with various substituents, as well as solvents. From the detailed analysis of the DFT results, we found that the electron donating dibenzyl amine group increased the electron population on the triazinyl ring, which decreased the rotational barrier of the C–N bond in the dithiocarbamate group attached to the triazinyl ring. The higher electron population on the triazine moiety stabilizes the partial double bond character of the S–C bond, which competitively excludes the double bond character of the C–N bond. Therefore, the rotational dynamics of the C–N bond in dithiocarbamates can be a sensitive probe to small differences in the electron population of substituents on sulfur.

Full text of DOI:10.1016/j.molstruc.2017.09.063

Accepted Manuscript
Hindered C-N bond rotation in triazinyl dithiocarbamates
Taesub Jung, Hee-Jin Do, Jongwoo Son, Jae Hee Song, Wansik Cha, Yeong-Joon
Kim, Kyung-Koo Lee, Kyungwon Kwak
PII:
S0022-2860(17)31250-4
10.1016/j.molstruc.2017.09.063
MOLSTR 24312
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 24 July 2017
Revised Date: 15 September 2017
Accepted Date: 18 September 2017
Please cite this article as: T. Jung, H.-J. Do, J. Son, J.H. Song, W. Cha, Y.-J. Kim, K.-K. Lee, K. Kwak,
Hindered C-N bond rotation in triazinyl dithiocarbamates, Journal of Molecular Structure (2017), doi:
10.1016/j.molstruc.2017.09.063.
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ACCEPTED MANUSCRIPT
Hindered C-N Bond Rotation in Triazinyl Dithiocarbamates
Taesub Junga,b, Hee-Jin Doc, Jongwoo Sonc, Jae Hee Songd , Wansik Chae, Yeong-Joon
Kimc*, Kyung-Koo Leef*, Kyungwon Kwaka,b*
aCenter for Molecular Spectroscopy and Dynamics, Institute for Basic Science (IBS), Seoul
02841, Republic of Korea
bDepartment of Chemistry, Korea University, Seoul 02841, Republic of Korea
cDepartment of Chemistry, Chungnam National University, Daejeon 34134, Republic of
Korea
dDepartment of Chemistry, Sunchon National University, Suncheon-si, Jeollanam-do 57922,
Republic of Korea
eNuclear Chemistry Research Division, Korea Atomic Energy Research Institute, Daejeon
34057, Republic of Korea
fDepartment of Chemistry, Kunsan University, Gunsan-si, Jeollabuk-do 54150, Republic of
Korea
* Corresponding authors. E-mail address: y2kim@cnu.ac.kr, kklee@kunsan.ac.kr,
kkwak@korea.ac.kr
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ABSTRACT
The substituent and solvent effects on the rotation around a C-N amide bond were studied for a
series of triazine dibenzylcarbamodithioates. The Gibbs free energies (ꢀG‡) were measured to be 16–
18 kcal/mol in DMSO-d6 and toluene-d8 using variable-temperature nuclear magnetic resonance (VT-
1H-NMR) spectroscopy. Density functional theory (DFT) calculations reproduced the experimental
observations with various substituents, as well as solvents. From the detailed analysis of the DFT
results, we found that the electron donating dibenzyl amine group increased the electron population on
the triazinyl ring, which decreased the rotational barrier of the C-N bond in the dithiocarbamate group
attached to the triazinyl ring. The higher electron population on the triazine moiety stabilizes the
partial double bond character of the S-C bond, which competitively excludes the double bond
character of the C-N bond. Therefore, the rotational dynamics of the C-N bond in dithiocarbamates
can be a sensitive probe to small differences in the electron population of substituents on sulfur.
Graphical Abstract
Highlights
· Triazine dibenzylcarbamodithioates were synthesized.
· The activation energies of the C-N bond rotation were measured by NMR methods.
· The Gibbs free energies were obtained to be 16–18 kcal/mol in DMSO-d6 and toluene-d8.
· DFT calculation provides the strong support about the experimental observations.
KEYWORDS
C-N bond rotational dynamics, VT-NMR, DFT calculation, Triazinyl derivative, Dithiocarbamate
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1. INTRODUCTION
1,3,5-Triazine derivatives have been used industrially as pharmaceuticals, pesticides, herbicides,
dyes, textiles, plastics, and rubber among other applications.1 Recently, they have also found
applications in organic electronic materials, such as in liquid crystals and organic light-emitting
diodes (OLEDs).2 Dithiocarbamate derivatives have been shown to have a wide range of applications
such as antibacterial and antifungal activities.3,4 When these two functional units are combined,
triazine-dithiocarbamate derivatives are formed, which have been reported to have excellent
tribological performances.5
Within triazine-dithiocarbamate derivatives, the central 1,3,5-triazinyl group is more electron
deficient than the phenyl and pyridyl moieties due to the three electronegative nitrogen atoms in the
ring. Moreover, there are three sites through which the electron population can be tuned by modifying
the substituents in the 1,3,5-triazinyl ring. The attached dithiocarbamates show restricted rotation
around the C-N bond, and the rate can be determined using variable-temperature nuclear magnetic
resonance (VT-NMR). The rotational dynamics of the C-N bond can be a sensitive probe to the
electronic structure around the C-N bond. Specifically, when combined with quantum chemical
calculations, the observed C-N bond rotational dynamics provides rich information about the chemical
environment around the C-N bond, such as the interactions with substituents or solvents, which play
essential roles in determining the ground and transition states structure.6,7,8
Many reports have focused on the effect of substituents on the nitrogen atom of the amide or
thioamide group. Similar studies have been performed recently using carbamates, thiocarbamates, and
dithiocarbamates. For all amide-like systems, it is generally accepted that electron-donating
substituents on the nitrogen atom restrict the rotation around the C-N bond, while electron-
withdrawing groups accelerate the rotation.9,10 Therefore, the substituents on the nitrogen atom
modulate the electron donating ability of the lone pair electrons on the nitrogen atom. On the other
hand, there has been relatively less investigation regarding substituent effects on the carbon atom of
the amide/thioamide unit or on the oxygen/sulfur atom of carbamates/thiocarbamates. Oxygen and
sulfur atoms can also donate their lone pair electrons to the central carbon, which will compete with
the lone pair electrons from the nitrogen atom. This competition is expected to cause different effects
on the rotational dynamics of the C-N bond.
In this study, we synthesized a number of triazine-dithiocarbamate compounds and modulated
the electron population on the central triazinyl ring through systematically adding dithiocarbamate
groups. Our density functional theory (DFT) calculations revealed good quantitative and qualitative
agreement with the experimentally determined rotational barriers. Based on the detailed analysis of
the DFT results, we found that the observed rotational dynamics about the C-N bond could shed light
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on subtle changes in the electron population of the triazinyl ring.
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2. SYNTHESIS, NMR, and COMPUTATIONAL METHODS
2.1 Synthesis
The synthesis of compounds 3, 4, and 5 is summarized in Fig. 1. Compound 3 is a major product
when cyanuric chloride is reacted with potassium dibenzylcarbamodithioate in the presence of
potassium carbonate in anhydrous THF. In contrast, we obtained compound 4 as a major product
when potassium carbonate was not used in a THF/water (3:1) mixture. Water can facilitate the acid
catalyzed decomposition of dibenzylcarbamodithioate, eventually generating dibenzylamines. The
effect of potassium carbonate in the synthesis of compound 3 can be explained by the retardation of
the decomposition of dibenzylcarbamodithioate, since it plays an important role in scavenging acid
impurities. For the synthesis of compound 5, neither the introduction of two amine groups first and
then carbamodithioate to the triazinyl ring nor the reverse was successful. Compound 5 could be
synthesized by the sequential substitution of cyanuric chloride, going through compound 1 and
compound 2.
2.2 NMR
Fig. 2 and Fig. S9-S12 show the VT-1H-NMR spectra of the benzyl (CH2) region of compounds
3-5 in Toluene-d8 and DMSO-d6. 1H-NMR and 13C-NMR spectra are provided in Fig. S1-S8 also. The
benzyl (CH2) signals appear around 5.0 ppm and 5.2 ppm in DMSO-d6, but in toluene-d8, their peaks
1
exhibit around 5.1 ppm and 5.5 ppm. The room temperature H-NMR spectrum of compound 4
exhibits two different benzyl (CH2) signals due to the slow rotation of the C-N bond in the
dithiocarbamate moiety. As the temperature is increased, the two peaks start to collapse and finally
merge into one sharp peak. This can be explained by the fast exchange of the unsymmetrical benzyl
1
groups caused by the rotation around the C-N bond in the dithiocarbamate. Similar VT H-NMR
spectral patterns were observed in the benzyl region for compounds 3 and 5 (Fig. S9-S12). The
coalescence temperatures of compounds 3, 4, and 5 were determined to be 376, 366, and 357 K in
DMSO-d6, and 364, 351, and 343 K in Toluene-d8, respectively. With the coalescence temperature
(K) and the chemical shift difference dv (in Hz) at room temperature, the activation energy can be
calculated using equation 1.
∆
G‡ = RTc[22.96 + ln(Tc/
∆v)]
[eq. 1]
c
The simulated spectra on the right side of Fig. 2 and Fig. S9-S12 were obtained by using line
shape analysis.11 This method provides exchange rates, k(s-1), corresponding to the rates of C-N bond
rotation in the dithiocarbamate. From the Eyring plots shown in Fig. S13-S14, the activation
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quantities,
∆
H‡,
∆
S‡, and
∆
G‡ were calculated and are listed in Table 1. Line shape analysis typically
generates more accurate
∆
G‡ values than that obtained from the coalescence temperature method.
Table 1 shows that the activation Gibbs free energy values obtained from the coalescence temperature
method are in good agreement with those obtained using line shape analysis.
2.3 Computational methods
All DFT calculations were performed using Gaussian 09.12 3-5 molecules were optimized at the
B3LYP13/6-311G(d) basis level, and the other molecules depicted in Fig. 3 were optimized at the
B3LYP/6-311+G(2d,p). The energetically most stable structure was assigned as the ground state (GS).
To determine the rotational transition state structure of all of compounds, the dihedral angle of S=C-
N-C was scanned with incremental step sizes as 10 degrees. At every step, only the dihedral angle was
fixed and other structural parameters were energetically optimized. The resulting potential energy
surface following the rotation of the dihedral angle (S=C-N-C) produced two structures that were
energetically most unstable, which were assigned as the rotational transition states (TS). TS structures
have only one negative frequency vibrational mode. Following the notation adopted from previous
studies regarding amide rotational dynamics, the two transition states can be defined as the syn- and
anti-conformer. The former places the C=S group and nitrogen lone pair electrons face to face, but the
latter involves the trans configuration between the two, as depicted in Fig. 4.
To determine the various thermodynamic properties such as enthalpy, entropy, and Gibbs free
energy for direct comparison with the experimental data, we performed vibrational frequency
calculations using the GS and TS structures at the same level of theory with structure optimization.
The Gibbs free energy difference between GS and TS was defined as the rotational activation Gibbs
energy. The details of Natural Bond Analysis (NBO) can be found in supporting information (Figure
S15, Table S1-S4).
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3. RESULTS and DISCUSSION
3.1 The effect from the addition of dithiocarbamate
As shown in Table 1, the activation Gibbs free energy of compounds 3, 4, and 5 decreased upon
replacing the dithiocarbamate with a dibenzylamino group on the triazinyl ring. Although the
observed differences were very small, the coalescence temperature and line-shape analysis methods
revealed nearly the same pattern regarding activation energies. Furthermore, the decreasing trend in
the rotational barriers of compounds 3 to 5 showed the same behavior in different solvents, despite
large differences in polarity. This indicated that the observed decreasing trend in the rotational barrier
was independent of solvent and dominated by substituent effects. To investigate the molecular origin
of the observed rotational barrier changes, we performed DFT calculations. The GS and TS structures
were used to calculate the rotational barriers in DMSO-d6 and toluene-d8 with the polarizable
continuum model (PCM) for the solvents.
The results are listed in Table 2. The rotational barrier through the syn-transition state was bigger
than that through the anti-transition state in all compounds. Thus, the anti-conformer will be the
dominant transition state with least activation barrier. This is primarily attributed to the electrostatic
repulsion between the lone pair electrons on the nitrogen atom and π electrons on the C=S bond in
syn-conformer. The calculated rotational barrier of these compounds decreased with increasing amine
groups attached to the triazinyl ring, which was in accord with the experimental observation listed in
Table 1; these results can be explained by the increased electron population on the triazinyl ring. In
other words, the electron-deficient character of the triazinyl ring decreased with increasing amine
substitution.
Usually, carbamates have smaller C-N rotational activation energies than similar amides due to
the decreased double bond character between the carbon and nitrogen atoms. Dithiocarbamates also
exhibit smaller C-N rotational barriers than thioamides. Carbamates or dithiocarbamates have another
oxygen or sulfur atom that can donate lone pair electrons to the carbon atom in the amide unit. The
lone pair electrons of oxygen or sulfur atom will compete to occupy the p orbital of the carbon atom
in the amide. Thus, the double bond character of the C-N bond will decrease, resulting in decreased
rotational activation energy. It is well known that substituents on nitrogen can modulate the electron
donating ability of nitrogen atom and rotational dynamics of the C-N bond. For the same reason,
substituents on sulfur or oxygen can also modulate the donation of their lone pair electrons to the
carbon atom in the amide unit. Because these lone pair electrons on nitrogen and oxygen/sulfur should
compete for the same p orbital on carbon, the donation of the lone pair electrons from sulfur or
oxygen to carbon will decrease the double bond formation between carbon and nitrogen. Thus, the C-
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N bond rotation in dithiocarbamates will be affected by the electron donating or accepting character of
the substituent on sulfur, that is, the triazinyl ring.
The lone pair on the nitrogen atom in dibenzylamino groups is in conjugation with the π system
on the triazinyl ring. In other words, dibenzylamino groups can work as π-electron donors to the
triazinyl ring. Amino groups are strong electron donating groups when attached to benzene rings.
However, it is not certain if amino groups show electron donating effects in triazinyl rings. To
quantitatively investigate the electron donating effect, natural population analysis(NBO) was
performed for each compound to account for the electron population change in the π electron system
with dibenzylamino groups. A detailed explanation regarding natural population analysis is provided
in the Supplementary data. Tables 3, S1, and S2 list the electron populations in the π electron system
of the triazinyl ring; a gradual increase with increasing dibenzylamino groups is noted. In addition,
1,3,5-triazine has approximately 6 electrons on their
ꢀ system, but compound 3 already possesses
more π electrons than six, indicating that the dithiocarbamate also works as an electron donating
group, but the electron donating ability is less than that of the dibenzylamino group.
The lone pair electrons on sulfur is in conjugation with the π* anti-bonding orbital of the triazine
moiety or the anti-bonding orbital of the C=S bond. The conjugation between the lone pair and π*
anti-bonding orbital of the triazinyl group is expected to be the highest in compound 3, where there is
no dibenzylamino group. In contrast, in compound 5 the lone pair of the sulfur atom and π* anti-
bonding orbital of the triazinyl ring interact the least because of the stronger electron donating ability
of the dibenzylamino group. To confirm the electron donating ability of sulfur towards the triazinyl
ring, the hyperconjugation energies were calculated and are compared in Fig. 5. In addition, we found
the same trend in bond length. Increasing orbital interactions mean stronger bonds and decreasing
bond lengths. In compound 3, the hyperconjugation toward the triazinyl group is stronger than that of
compound 5 by about ~10 kcal/mol, and the S-Ctriazine bond length is the shortest. Combined with the
electron population results presented in the previous section, these results reveal that the increased
electron population of substituents on the sulfur atom prevents the electron donation from sulfur to
substituents, or the triazinyl ring in this case.
3.2 Substituent effect of rotational barrier in 1,3,5-trazinyl compounds
To check the substituent effect through the ring, we calculated a couple of simplified molecular
systems in Fig. 3. The molecules consist of triazinyl ring, but have different substituents. The
substituents can be categorized by a strong electron donating group (-N(CH3)2), moderate electron
donating groups (-CH3, -CH=CH2), moderate electron withdrawing groups (-F, -Cl, -Br) and strong
electron withdrawing groups (-CF3, CN, NO2, NO), which can be ordered by Hammett σ constant14.
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Hammett constants were obtained through experimental observation and there is a linear relationship
with the equilibrium constants as in equation 2 and with the rate constants as in equation 3, relating
the reaction of benzoic acid derivatives.
log (K/ K0) = σρ
log (k/ k0) = σρ
[eq. 2]
[eq. 3]
In Fig. 6, we compare the Hammett constant and calculated rotational barrier of the small
molecules in Fig. 3, and we can observe the clear correlation not only σpara (para substitution) but also
σmeta (meta substitution). The rotational barriers were obtained from the potential energy scan method
as shown in Figure S16-S20. When the substituent has more tendency to withdraw electron and
therefore, has a larger positive Hammett constant value, the rotational barrier energy is bigger. This
result shows how the electron population on the triazinyl ring strongly affects the S=C-N-R dihedral
rotation. The more electron population on triazinyl ring, the faster the rotation is, and vice versa.
3.3 The anti-correlation effect of electron population of S-substituent and amide rigidity
The electron-rich central ring blocks electron donation from the sulfur atom in thiocarbamates to
the triazinyl ring, so there is a better chance for the sulfur atom next to the triazinyl ring to donate its
lone pair to the π* anti-bonding orbital of the C=S bond. In compound 3, the lone pair electrons of
sulfur mainly interact with the triazinyl ring with little contribution from the interaction between
sulfur and C=S. However, substitution with a dibenzylamino group induces the increasing interaction
between sulfur and C=S. Finally, compound 5 exhibits a comparable hyperconjugation energy and
bond length as shown in Fig. 5. These hyperconjugation energies can be interpreted as being
proportional to partial double bond characters, which exist around the sulfur atom attached to the
triazinyl ring.
As shown in Fig. 5, bond length and hyperconjugation strongly correlated. An anti-correlation
between electron population of S-substituent and rigidity of amide bond in the dithiocarbamate was
also observed. When the sulfur atom in dithiocarbamates forms a bond with π electron-rich
substituents, the rotational barrier of the amide in that compound decreases, which correctly reflects
the observed trend in rotational barriers. On the other hand, if the sulfur atom donates its electrons to
its substituents, the rotation becomes relatively difficult.
In Fig. 7, we propose an explanation of how the π electron population of the S-substituent can
alter the rotational barrier. If the substituent has a higher π electron population, sulfur cannot form
structure b and structure c becomes dominant. Because the origin of amide rigidity is the partial
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double bond between the nitrogen and carbon, structure c prevents the conjugation with nitrogen, thus
decreasing the rotational barrier.
3.4 Solvent effects
All compounds showed almost the same solvent dependence in rotational dynamics. The
activation Gibbs free energy of compounds 3, 4, and 5 in DMSO-d6 were ca. 1 kcal/mol bigger than
those in Toluene-d8. This result was in good agreement with the measurement reported by Pontes et
al.6 Specifically, they reported almost the same rotational barrier increase in methyl N,N-
dimethyldithiocarbamate from benzene to DMSO-d6. This solvent dependence can be explained by
the contribution of the dipolar resonance structure in the ground state. Due to the N-C=O N+=C-O-
resonance, the increase in polarity stabilizes the dipolar resonance structure and increases the double
bond character between nitrogen and carbon.3 Energetically, the energy of the GS decreases because
of dipole stabilization in polar solvents. As can be seen in Fig. 7, the additional dipolar resonance
structure of dithiocarbamates would increase the dipolar property in the GS. This is different from
simple amides, whose transition states do not show explicit charge separation; however, structure c in
Fig. 8 also can contribute to the rotational transition state and result in charge separation and the
resulting dipole moment in the TS. Furthermore, the complex molecular structure of compounds 3-5
does not allow simple prediction of dipole moments based only on the dipolar resonance structure
around the amide unit. Thus, we calculated the dipole moment in the GS and TS of each compound
(Table S4). As expected, compound 4 and 5 showed bigger dipole moments in the GS than in their
rotational TS. Polar solvents would stabilize the GS more than the TS, resulting in an increased
rotational barrier. In compound 3, the TS has a bigger dipole moment than the GS. The symmetric
structure in the GS likely partially cancels the dipole moment from each amide unit. Even if
compound 3 shows the opposite behavior in dipole moment, the calculated solvent dependence still
reflects the correct trend, where the rotational barrier increases in more polar solvents. Further studies
are required to completely understand the solvent dependence.
Generally, calculated ∆S values are negative for the C-N bond rotation of amides, thioamides,
carbamates, and dithiocarbamates since the transition states lose one vibration mode in the gas phase.
The experimentally observed positive
∆
S‡ may represent a more organized solvation shell for the
ground state, not only in DMSO-d6, but also in Toluene-d8. This is again in good agreement with that
for methyl N,N-dimethyldithiocarbamate.6 The activation entropy was a very small positive value for
all compounds and solvents, which suggests a more organized structure complexed with the solvent
molecules in the ground state. In contrast, DFT calculations in the gas phase and solvents revealed
that the activation entropy was small and negative, due to the loss of one vibrational degree of
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freedom corresponding to rotational motion. However, it is expected that planar toluene-d8 molecules
can interact with the planar dithiocarbamate group in the ground state, which would produce a more
organized ground state structure. DMSO-d6 is also known to form a dimer structure and the planar
structure of DMSO-d6 will have stronger interactions with the planar dithiocarbamate units.15 Thus,
the experimentally measured positive entropy values represent a strong interaction between the
dithiocarbamate group and solvents with planar structures.
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4. EXPERIMENTAL SECTION
4.1 General procedure
All NMR measurements were performed on a Bruker Fourier (1H 300 MHz, 13C 75 MHz) or
Bruker AVANCE Ⅲ 600 (13C 150 MHz) spectrometer. All spectra were measured at ambient
temperature (298 K) unless otherwise noted. The IR spectrum was recorded by using JASCO FT/IR-
4000 spectrometer in the region 4000–400 cm−1 with sample in KBr pellet. Mass spectra were
recorded on an Applied Biosystems Voyager DE-STR MALDI-TOF MS.
4.2 VT-NMR
Dynamic 1H-NMR experiments were performed on a BrukerAVANCE Ⅲ 600 MHz
spectrophotometer. NMR samples were prepared by dissolving the dithiocarbamates (15 mg) in 0.7
mL of DMSO-d6 (min 99.8 atom %D) or 0.75 mL of toluene-d8 (min 99.8 atom %D) in 5-mm o.d.
NMR tubes. Typical conditions included a pulse length of 10.7 us, 8 scans, 1 s of delay time, a sweep
width of 6000 Hz, and 65 K of data points. The variable-temperature probe was calibrated against
methanol and ethylene glycol standards. The line shape analysis was carried out using a standard
diagonalization program in the Mathematica suite.11
4.3 Solvents and reagents
All of the starting chemicals were used as received from Aldrich and TCI Chemical. Deuterated
NMR solvents were purchased from ARMAR Chemicals.
4.4 Synthetic procedures
Potassium dibenzylcarbamodithioate
Carbon disulfide (0.4 mL) was added to a solution of dibenzylamine (0.7 mL) and potassium
hydroxide (0.369 g) in THF (6 mL). After 2 h, the solvent was removed under reduced pressure and
the residue was recrystallized from ethyl acetate and hexane to produce 1.4 g of the product.
Synthesis of 1,3,5-triazine derivatives
2-dibenzylamino-4,6-dichloro-1,3,5-triazine (1)
To a solution of dibenzylamine (0.5 mL, 1.63 mmol) in THF (4 mL), potassium carbonate (0.749
g, 5.42 mmol) and cyanuric chloride (0.5 g, 2.71 mmol) were added. The mixture was stirred at room
temperature for 1 h. After adding water, the solution was extracted with ethyl acetate. The ethyl
acetate phase was separated, dried over MgSO4, and then evaporated to produce a white solid (0.558
1
g, 99%). Mp: 98-102 °C. H NMR (300 MHz, DMSO-d6) 4.77 (4H, s, NCH2), 7.25-7.34 (10H, m,
CHarom).
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4-chloro-6-dibenzylamino-1,3,5-triazin-2-yl dibenzylcarbamodithioate (2)
Compound 1 (0.3 g, 0.87 mmol) was added to a solution of potassium carbonate (0.12 g, 0.87
mmol) and potassium dibenzylcarbamodithioate (0.27 g, 0.87 mmol) in THF (10 mL). The reaction
mixture was stirred at room temperature for 16 h. The mixture was washed with 1 M aqueous
NaHCO3 (10 mL) and then extracted with 30 mL of ether. The combined organic layer was washed
with brine, dried with MgSO4 and then concentrated by evaporation. The product was purified by
1
flash silica gel chromatography to give a yellow solid (0.40 g, 80%). Mp: 128.7-130 °C. H NMR
(300 MHz, Toluene-d8) 4.49 (4H, d, J=5.0 Hz, NCH2), 4.70 (2H, s, SCNCH2), 6.98-7.08 (20H, m,
CHarom).
1,3,5-triazine-2,4,6-triyl tris(dibenzylcarbamodithioate) (3)
Cyanuric chloride (0.184 g,
1
mmol) was added to
a
solution of potassium
dibenzylcarbamodithioate (0.934 g, 3 mmol) and potassium carbonate (0.414 g, 3 mmol) in THF (30
mL) at 0 °C. The reaction mixture was stirred at room temperature for 12 h. The mixture was washed
with 1 M aqueous NaHCO3 (10 mL) and then extracted with ether (30 mL). The combined organic
layer was washed with brine, dried with MgSO4, and then concentrated by rotary evaporation. The
product was purified by column chromatography on silica gel using ethyl acetate to produce a yellow
1
solid (0.725 g, 82%). Mp: 138.2 °C. H NMR (300 MHZ, CDCl3) 5.00 (6H, s, CH2), 6.27 (6H, S,
CH2), 7.05-7.55 (30H, m, CHarom). 13C NMR (75 MHz, CDCl3) 55.8, 58.2, 127.3, 127.9, 128.4, 128.9,
129.2, 134.1, 134.5, 178.5, 183.5. IR (KBr): ν 3413, 1469, 1241 cm-1. Mass(MALDI) m/z calcd for
C48H42N6S6 ([M-CS2N(CH2C6H5)2]) 622.1306 ; found : 622.1979.
6-dibenzylamino-1,3,5-triazine-2,4-diyl bis(dibenzylcarbamodithioate) (4)
Cyanuric chloride (0.19 g, 1.02 mmol) was added to a solution of potassium
dibenzylcarbamodithioate (0.95 g, 3.05 mmol) in THF (12 mL) and water (4 mL) at 0 °C. The
reaction mixture was stirred for 12 h at 0 °C, treated with 1 M aqueous NaHCO3 (10 mL), and then
extracted with ether (30 mL). The combined organic layers were washed with brine, dried over
MgSO4, and concentrated by evaporation. The product was purified by flash silica gel
chromatography to produce a yellow solid (0.612 g, 73.5%). Mp: 128 °C. 1H NMR (300 MHz, CDCl3)
4.65 (4H, s, NCH2), 4.99 (4H, s, SCH2), 5.19 (4H, s, SCH2), 7.07-7.41 (30H, m, CHarom). 13C NMR
(150 MHz, CDCl3) 48.3, 55.6, 57.9, 127.3, 127.7, 127.8, 128.23, 128.24, 128.7, 128.1, 128.8, 129.0,
134.6, 134.8, 136.3, 163.4, 177.7, 186.8. IR (KBr): ν 3413, 1545, 1465 cm-1. Mass(MALDI) m/z
calcd for C47H42N6S4 ([M+H+]) 819.2354 ; found :819.3611.
4,6-bis(dibenzylamino)-1,3,5,-triazin-2-yl dibenzylcarbamodithioate (5)
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Compound 2 (0.4 g, 0.70 mmol) was added to a solution of dibenzylamine (0.13 mL, 0.70 mmol)
and potassium carbonate (0.097 g, 0.70 mmol) in THF (3 mL). The reaction mixture was stirred at
55 °C for 5 h. The mixture was washed with 1 M aqueous NaHCO3 (10 mL) and extracted with ether
(30 mL). The combined organic layers were washed with brine, dried with MgSO4, and purified by
1
flash column chromatography to produce a yellow solid product (0.324 g, 63%). Mp: 108.5 °C. H
NMR (300 MHz, CDCl3) 4.60 (2H, s, NCH2), 4.68 (2H, s, NCH2), 4.90 (2H, s, SCH2), 5.09 (2H, s,
SCH2), 6.96-7.33 (30H, m, CHarom). 13C NMR (150 MHz, CDCl3) 48.3, 48.6, 55.4, 57.6, 127.6, 127.3,
127.5, 127.8, 128.1, 128.3, 128.49, 128.50, 128.54, 128.6, 135.1, 137.5, 137.7, 164.8, 177.3, 189.4. IR
(KBr): ν 3120, 1542, 1492 cm-1. Mass(MALDI) m/z calcd for C46H42N6S2 ([M+H+]) 743.2912 ; found :
743.4107.
5. ACKNOWLEDGMENTS
This research was supported by the Nuclear Research and Development Program of the National
Research Foundation of Korea [Grant No. NRF-2016M2A8A5021714]. Y.-J. Kim acknowledges
support from the Research Fund at Chungnam National University. We thank Mr. Shinho Lee for help
with preliminary experiments.
6. SUPPLEMENTARY DATA
Supplementary data (NMR, line shape analysis, natural bond analysis and dipole moment of
states) associated with this article can be found in the online version.
7. REFERENCE and NOTES
1. G. Blotny, Recent applications of 2,4,6-trichloro-1,3,5-triazine and its derivatives in organic
synthesis, Tetrahedron, 62 (2006) 9507-9522.
2. L. L. Falher, O. Ben Ayad, O. Ziyaret, A. Mamontov, C. Botuha, S. Thorimbert, F.
Slowinski, Access to Pyridyl-Substituted 1,3,5-Triazines from 4H-Pyrido[1,3]oxazin-4-ones via a
Cyclocondensation Process, J. Org. Chem. 27 (2014) 677-678.
3. N. Ohtake, H. Imamura, H. Jona, H. Kiyonaga, A. Shimizu, M. Moriya, H. Sato, M. Nakano,
R. Ushijima, S. Nakagawa, Novel dithiocarbamate carbapenems with anti-MRSA activity, Bioorg.
Med. Chem. 6 (1998) 1089-1101.
4. V. D. Lunagariya, R. M. Desai, V. H. Shah, Studies on bioactive bis-1,3,5-triazinyl
dithiocarbamates, J. Serb. Chem. Soc. 72 (2007) 635-641.
5. (a) W. Zhan, Y. Song, T. Ren, W. Liu, The tribological behaviour of some triazine–
dithiocarbamate derivatives as additives in vegetable oil, Wear, 256 (2004) 268-274. (b) X. Zeng, J.
14

ACCEPTED MANUSCRIPT
Li, X. Wu, T. Ren, W. Liu, The tribological behaviors of hydroxyl-containing dithiocarbamate-
triazine derivatives as additives in rapeseed oil, Tribology International 40 (2007) 560-566. (c) H. Wu,
J. Li, H. Ma, T. Ren, The tribological behaviours of dithiocarbamate-triazine derivatives as additives
in mineral oil, Surf. Interface Anal. 41 (2009) 151-156.
6. R. M. Pontes, E. A. Basso, F. P. Santos, Medium Effect on the Rotational Barrier of
Carbamates and Its Sulfur Congeners, J. Org. Chem. 72 (2007) 1901-1911.
7. K. B. Wiberg, D. J. Rush, Solvent Effects on the Thioamide Rotational Barrier:ꢁ An
Experimental and Theoretical Study, Am. Chem. Soc. 123 (2001) 2038-2046.
8. S. Jayasundera, W. F. Schmidt, C. J. Hapeman, A. Torrents, Influence of the Chemical
Environment on Metolachlor Conformatrions, J. Agric. Food. Chem. 47(10) (1999) 4435-4442.
9. D. S. Bradley, M. G. DeeAnne, J. E. D. Carlisle, J. N. Kieran, M. S. Leslie, C. T. James,
Substituent effects on the barrier to carbamate C–N rotation, Tetrahedron Lett. 45 (2004) 2747-2749.
10. J. D. Martin, C. F. Christopher, J. Marco, P. M. Jeremiah, D. S. Bradley, W. Olaf, Unusually
Low Barrier to Carbamate C−N Rotation, J. Org. Chem. 67 (2002) 3949-3952.
11. Y.-J. Kim, A. Streitwieser, A. Chow, G. Fraenkel, Aggregation and C−N Rotation of the
Lithium Salt of N,N-Dimethyldiphenylacetamide, Org. Lett. 1(13) (1999) 2069-2071.
12. Gaussian 09, Revision D.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M.
A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M.
Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M.
Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T.
Vreven, J. A. Montgomery Jr, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N.
Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S.
Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken,
C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C.
Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J.
J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J.
Fox, Gaussian Inc., Wallingford CT, 2009.
13. A. D. Becke, Density‐functional thermochemistry. III. The role of exact exchange, J. Chem.
Phys. 98 (1993) 5648-5652.
14. L. P. Hammett, The Effect of Structure upon the Reactions of Organic Compounds. Benzene
Derivatives, J. Am. Chem. Soc. 59(1) (1937), 96-103.
15. K. Kwak, D. E. Rosenfeld, J. K. Chung, M. D. Fayer, Solute−Solvent Complex Switching
Dynamics of Chloroform between Acetone and Dimethylsulfoxide−Two-Dimensional IR Chemical
Exchange Spectroscopy, J. Phys. Chem. B. 112 (2008) 13906-13915.
15

ACCEPTED MANUSCRIPT
16. H. Maouati, M. A. K. Sanhoury, D. Merlet, I. Chehidi, Bis(thiocarbamates): Synthesis and
Substituent Effects on the Barrier to N-CO Rotation, Heteroatom Chem. 26(6) (2015) 391-396.
17. (a) M. Toumi, M. A. Sanhoury, M. Bordeau, N. Raouafi, K. Boujlel, Hindered Rotation in
Some Organic Dithiocarbamates, Phosphorus Sulfur Silicon Relat. Elem. 188(7) (2013) 920-930. (b)
A. Shockravi, M. Kamali, R. Jafari, A Simple and Eco-Compatible One-Pot Synthesis of New
Symmetrical Dithiocarbamate Podands and Their Dynamic NMR Studies, Phosphorus Sulfur Silicon
Relat. Elem. 188(9) (2013) 1271-1280. (c) A. Shockravi, M. Kamali, F. Sorkhei, R. Jafari, A simple
and efficient synthesis and dynamic NMR studies of some new podands of dithiocarbamates formed
from bis(naphthyl) derivatives, Heteroatom Chem. 22(5) (2011) 659-668
18. D. H. Williams, I. Fleming, Spectroscopic Methods in Organic Chemistry; McGraw-Hill,
UK, 1989.
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FIGURES
Figure 1.
Figure 1. Synthesisa and structures of compounds 3, 4, and 5.
aReaction Conditions: (i) 3 eq of potassium carbonate with potassium dibenzylcarbamodithioate
and cyanuric chloride in THF, 25 °C, 12 h; (ii) 3 eq of potassium dibenzylcarbamodithioate and
cyanuric chloride in THF with water, 0 °C, 12 h; (iii) 1 eq of potassium carbonate and 1 eq of
dibenzylamine in THF, RT, 1 h; (iv) 1 eq of potassium dibenzylcarbamodithioate, 1 eq of potassium
carbonate, and 1 eq of 1 in THF, RT, 16 h; (v) 1 eq of potassium carbonate with dibenzylamine and 1
eq of 2 in THF, 55 °C, 5 h.
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Figure 2.
Figure 2. VT-1H-NMR of Compound 4 in (a) DMSO-d6 and (b) Toluene-d8. Two distinct peaks
at low temperature are from CH2(A) and CH2(B).
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Figure 3.
Figure 3. The substituents of simplified small molecules
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Figure 4.
Figure 4. The structure of (a) syn-conformer, and (b) anti-conformer.
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Figure 5.
Figure 5. Hyperconjugation effects and bond lengths with sulfur. Each bar represents the
hyperconjugation energy. Black square and red circles are bond lengths.
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Figure 6.
Figure 6. The correlation between Hammett σpara and σmeta constants and calculated rotati
onal barrier energy with B3LYP/6-311+G(2d,p).
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Figure 7.
Figure 7. A possible explanation of C-N rotational barrier changes due to electron population
of 1,3,5-triazinyl group.
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TABLES
Table 1.
In DMSO-d6
In Toluene-d8
a
b
a
b
ꢀH≠ a
ꢀS≠ a
ꢀG≠
ꢀG≠
ꢀH≠ a
ꢀS≠ a
ꢀG≠
ꢀG≠
Tc
Compound
362
Tc
362
[kcal mol-1]
[cal mol-1k-1]
[kcal mol-1]
[kcal mol-1]
[kcal mol-1]
[cal mol-1k-1]
[kcal mol-1]
[kcal mol-1]
3
4
5
19.0±0.3
18.4±0.2
17.9±0.3
2.7±0.9
2.1±0.6
1.9±0.8
18.0±0.6
17.6±0.4
17.2±0.6
17.9
17.7
17.2
18.2±0.3
19.0±0.5
17.8±0.3
3.6±0.9
7.3±1.3
5.1±0.9
16.9±0.7
16.3±0.9
16.0±0.6
16.9
16.4
16.0
Table 1. Thermodynamic properties of rotation of Compound 3, 4, and 5.
aThe values obtained from line shape analysis. bThe value obtained from coalescence temperature.
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Table 2.
In DMSO-d6
ꢀS
In Toluene-d8
In Gas phase
ꢀS
Transition
state
ꢀH
ꢀG
ꢀH
ꢀS
ꢀG
ꢀH
ꢀG
Compound
[cal mol-1k-
[cal mol-1k-
[cal mol-1k-
[kcal mol-1]
[kcal mol-1] [kcal mol-1]
[kcal mol-1] [kcal mol-1]
[kcal mol-1]
1
1
1
]
]
]
3
4
5
3
4
5
19.46
17.08
16.33
16.94
16.05
13.99
-5.88
-5.95
-7.41
-7.00
-4.70
-6.56
21.22
18.85
18.54
19.02
17.45
15.94
18.81
16.66
15.95
16.23
15.32
13.55
-7.79
-6.34
-7.67
-7.25
-6.90
-6.50
21.13
18.06
18.24
18.40
17.38
15.04
18.47
15.88
15.75
15.86
14.69
12.65
-4.78
-6.69
-5.43
-6.83
-4.83
-3.65
19.90
17.87
17.37
17.90
16.13
13.74
Syn
Anti
Table 2. Thermodynamic properties of rotation of compound 3, 4, and 5 from B3LYP/6-311G(d)
in DMSO-d6, toluene-d8, gas phase.
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Table 3.
1,3,5-triazine Compound 3 Compound 4 Compound 5
π* π* π* π*
5.031 0.961 5.201 1.344 5.155 1.439 5.193 1.444
5.992 6.545 6.594 6.636
Orbital of
triazine
π
π
π
π
Natural
Electron
Population
Table 3. Electron population of
ꢀ
system on triazinyl ring from NBO 3.1 within Gaussian 09
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Highlights
· Triazine dibenzylcarbamodithioates were synthesized.
· The activation energies of the C-N bond rotation were measured by NMR methods.
· The Gibbs free energies were obtained to be 16–18 kcal/mol in DMSO-d6 and toluene-d8.
· DFT calculation provides the strong support about the experimental observations.