Crystal structure and DFT studies of 4-methyl-N-(1-phenylethyl)-N=-(1-phenylethylidene)benzenesulfonohydrazide: Evidence of a carbene insertion in the formation of acetophenone azine from acetophenone p-Toluensulfonylhydrazone

Article abstract of DOI:10.1139/cjc-2016-0183

The crystal structure of 4-Methyl-N-(1-phenylethyl)-N=-(1-phenylethylidene) benzene sulfonohydrazide is disclosed, which is obtained from direct reaction between acetophenone tosylhydrazone and potassium tert-butoxide. Reaction mechanisms and the corresponding energy barriers were assessed through DFT calculations at the B3LYP/6-31G(d,p) level of theory and showed that this compound plays an important role as an intermediate in the formation of acetophenone azine from acetophenone p-Toluensulfonylhydrazone through a carbene insertion on this last compound.

Full text of DOI:10.1139/cjc-2016-0183

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Crystal Structure and DFT Studies of 4ꢀMethylꢀNꢀ(1ꢀphenylethyl)ꢀ
N´ꢀ(1ꢀphenylethylidene)benzenesulfonohydrazide. Evidence of a
carbene insertion in the formation of acetophenone azine from
acetophenone pꢀtoluensulfonylhydrazone.
Rocío A. Valencia, Víctor M. Apolonio, Guillermo CaballeroꢀGarcía, Diego Martínezꢀ
Otero, Joaquín BarrosoꢀFlores and Erick CuevasꢀYañez*
Centro Conjunto de Investigación en Química Sustentable UAEMꢀUNAM. Carretera
TolucaꢀAtlacomulco Km 14.5, Toluca, Estado de México, 50200, Mexico.
*Corresponding author. Universidad Autónoma del Estado de México. Tel. +52 722 276 66
10; fax: +52 722 180 62 17, eꢀmail: ecuevasy@uaemex.mx.

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Abstract. The crystal structure of 4ꢀMethylꢀNꢀ(1ꢀphenylethyl)ꢀN´ꢀ(1ꢀphenylethylidene)
benzene sulfonohydrazide is disclosed, which is obtained from direct reaction between
acetophenone tosylhydrazone and potassium tertꢀbutoxide. Reaction mechanisms and the
corresponding energy barriers were assessed through DFT calculations at the B3LYP/6ꢀ
31G(d,p) level of theory and showed that this compound plays an important role as
intermediate in the formation of acetophenone azine from acetophenone pꢀ
toluensulfonylhydrazone through a carbene insertion on this last compound.
Keywords. tosylhydrazone, azine, sulfonohydrazide, carbene insertion.

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Introduction
Tosylhydrazones have attracted the interest of organic synthetic chemists because these
compounds represent a practical source of both carbene and carbenoid species, in addition
to their easy availability.1 However, the reactions with tosylhydrazones sometimes present
the byꢀproduct formation problem, affording a mixture of products where the azines are the
most commonly found compounds in this kind of reactions. According to Kirmse,2 two
possible mechanistic pathways can explain the azine formation from diazoalkanes which in
turn are generated from the fragmentation of tosylhydrazones under basic conditions. In the
first instance, a dimerization between two molecules of diazoalkane 2 occurs giving the
cyclic derivative 6 which eliminates nitrogen to yield the corresponding azine 5 (scheme
1).3,4 On the other hand, diazoalkane 2 reacts with carbene 3 which is produced by nitrogen
extrusion of diazoalkane 2 with the subsequent azine formation.5 A third mechanism was
proposed by Sha and Wei, based on a direct carbene insertion on the pꢀtoluensulfonyl
hydrazone moiety, followed by an eliminationꢀreduction process of the sulfonyl group.6
Insert Scheme 1
In the course of our studies about carbenes and carbenoids derived from pꢀtoluensulfonyl
hydrazones, we occasionally observed the formation of azines, particularly in reactions
with basic and weak nucleophiles at low concentrations.7 A special process that drew our
attention is the reaction of acetophenone tosylhydrazone 8 with some nucleophiles that
gave complex mixtures under diverse conditions using potassium tertꢀbutoxide as base. The
isolation of some intermediates inspired us to examine this process in detail in order to find

Page 4 of 23
a rational reaction mechanism which could describe the azine formation from
tosylhydrazones to improve the carbene generation from these precursors. Herein is
presented a summary of our recent successful endeavors in this area.
Results and discussion
Through a careful analysis, we noted that direct reaction between acetophenone
tosylhydrazone 8 and potassium tertꢀbutoxide afforded a mixture of acetophenone azine 10
and a compound which was identified by the conventional spectroscopic techniques as 4ꢀ
MethylꢀNꢀ(1ꢀphenylethyl)ꢀN´ꢀ(1ꢀphenylethylidene) benzene sulfonohydrazide 9 (scheme
2). Optimizing conditions, compound 9 was obtained as only reaction product in 80%
yield, similar to that observed by Sha and Wei using NaOH.6 Since compound 9 was a
crystalline solid, it was studied by Xꢀray crystallography, and some interesting features
were revealed therein.
Insert Scheme 2
Singleꢀcrystal Xꢀray diffraction analysis was performed for compound 9 confirming the
spectroscopic results. An ORTEP and atom labeling diagram of compound 9 is presented
in Figure 1. Crystallographic data and structural refinement parameters of 9 are
summarized in table 1 and relevant bond lengths and angles data are collected in table 2.
Crystals of compound 9 were grown by slow evaporation of a dichloromethaneꢀhexane
mixture, crystallizing in the orthorhombic system under a centrosymmetric space group
Pbca (Figure 1), with 8 molecules in the unit cell. Compound 9 crystallized as a racemic
mixture, in Figure 1 the Rꢀenantiomer is shown. The conformation around the imine group

Page 5 of 23
is E, and it is confirmed by the dihedral angle N(1)ꢀN(2)ꢀC(9)ꢀC(11) with a value of
178.8(2) degrees.
Insert Figure 1
Insert Table 1
Insert Table 2
Compound 9 bears a part of the pꢀtoluenesulfonylhydrazone fragment which is similar to
other Nꢀnon hydrogen substituted, pꢀtoluenesulfonyl hydrazones described in literature.8ꢀ12
For example, the bond distance N(1)ꢀN(2) is 1.447 Å is in the range 1.374 to 1.462 Å in
this kind of compounds and depends on the nature of the substituents on the nitrogen
atoms. However, a noteworthy characteristic is that compound 9 presents weak CꢀHꢀꢀꢀO
type interactions in the crystalline structure, forming a dimer (Figure 2), the distance O(1)ꢀ
H8 is 2.552 Å, slightly lower than the sum of their van der Waals radii (1.62 Å).
Insert Figure 2
The isolation and unequivocal identification of compound 9 confirms the previous
observations made by Sha and Wei6 and suggests that this compound is an intermediate in
the azine formation from diazoalkanes derived from pꢀtoluenesulfonylhydrazones, because
subsequent experiments on compound 9 with excess potassium tertꢀbutoxide demonstrated
that acetophenone azine 10 was formed as only reaction product. Moreover, sulfinate

Page 6 of 23
elimination in compound 9 is also possible using SiO2 instead of potassium tertꢀbutoxide
(Scheme 2).
In order to get insights on the reaction mechanism, four reaction paths depicted in scheme 3
were assessed through computational chemistry methods. Reaction profiles for mechanisms
1, 2 and 3 are presented in figure 4.
Insert Scheme 3
Insert Figure 4
For mechanism 1, TS1-1 was found in which a molecule of 2 attacks a second one with
simultaneous elimination of nitrogen, the activation barrier found for this step was 35.28
kcal molꢀ1 with a reaction free energy of ꢀ68.79 kcal molꢀ1 indicating a spontaneous
reaction. At first we though that TS1-1 could yield intermediate 11 (scheme 3) which
consecutively could release a nitrogen molecule to afford 5, but that intermediate was not
found and this direct mechanism was confirmed analyzing the IRC results (SI).
On the other hand, mechanism 2 was also explored, in which diazo compound 2 attacks
carbene 3 to directly yield 5 through a simple addition step via transition state TS2-2.
Activation barrier for this addition was calculated to be 25.89 kcal molꢀ1 (respect to the
starting materials). Despite the fact that the barrier height for TS2-2 is lower than that for
TS1-1, mechanism 2 is firstly promoted by the formation of carbene 3 from nitrogen
release in 2. The activation energy needed for such elimination was found to be 31.59 kcal

Page 7 of 23
molꢀ1 trough transition state TS1-2. Therefore, when the reaction proceeds, TS1-1 and TS1-
2 compete to yield the corresponding products. Considering that the rate determining steps
for mechanisms 1 and 2 are given by TS1-1 (35.28 kcal molꢀ1) and TS1-2 (31.59 kcal molꢀ
1), respectively, with similar energies, it may be possible that both mechanisms operate in
the formation of compound 5.
The third mechanism was also studied. In order to find the [3+2]ꢀlike transition state TS1-
3, the unrestricted functional UB3LYP was used in combination with the
guess=(mix,always) keywords, yielding an activation free energy of 46.87 kcal molꢀ1.
Intermediate 12 was found in the potential energy surface, which after nitrogen release
afforded azine 5 through TS2-3 (25.06 kcal molꢀ1). The first barrier height for this
mechanism is larger in comparison with the two previous mechanisms, pointing that
although this mechanism is possible it may not occur when lowerꢀbarrier transition states
are available to.
These results are in agreement and complement previous kinetics studies made by Bethell
and coworkers.5,13,14
For mechanism 4, addition of 1 in its anion form to carbene 3 yielded TS1-4 (5.87 kcal
molꢀ1, figure 5). After several attempts we could not locate intermediate 7 as a stationary
point. The IRC path indicates that addition of carbene 3 should occur simultaneously with
4ꢀtoluensulfinate elimination. Further analysis of the RMS gradient norm along the IRC
path (figure 6), shows the presence of 7 as a hidden intermediate, which appears as a dip in
this curve. Hidden intermediates are not stationary points on the potential energy surface,

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but modifications in the reaction conditions or in the substitution pattern can make them
actual intermediates and may also be isolated, which is the case for isolated compound 9.
Insert Figure 5
Insert Figure 6
Considering the first activation energy from the four mechanisms we studied, it can be
concluded that the most plausible mechanism that drives the transformation under study is
mechanism 4 (5.87 kcal molꢀ1) once the carbene 3 is formed. As for this reaction to occur it
is necessary the formation of 3 (31.59 kcal molꢀ1), mechanism 4 takes place together with
the second part of mechanism 2.
On the other hand, the reaction between diazoalkanes with nucleophilic stable carbenes to
give azines directly,15 as well as the rhodium carbenoid insertions on phenylhydrazones,16
could be extended to diazoalkanes derived from tosylhydrazones, and together with these
last elements, indicate that a carbene insertion occurs on the tosylhydrazone tetrahedral
nitrogen which explain the formation of compound 9 as a possible intermediate in the
generation of the corresponding acetophenone azine.
Conclusion
In conclusion, this report shows the crystal structure of 4ꢀMethylꢀNꢀ(1ꢀphenylethyl)ꢀN´ꢀ(1ꢀ
phenylethylidene) benzene sulfonohydrazide 9 which not only complements and extends
the results of Sha and Wei,6 but also contributes to understanding of the mechanism of

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azine formation from pꢀtoluenesulfonylhydrazones through theoretical calculations derived
thereof that will help to control this kind of processes.
Experimental
General remarks
The starting materials were purchased from SigmaꢀAldrich and were used without further
purification. Solvents were distilled before use. Silica plates of 0.20 mm thickness were
used for thinꢀlayer chromatography. Melting points were determined with a Krüss Optronic
1
13
melting point apparatus and they are uncorrected. H and C NMR spectra were recorded
using a Bruker AVANCE 300 spectrometer; the chemical shifts (δ) are given in ppm
relative to tetramethylsilane (TMS) as the internal standard (0.00). For analytical purposes
the mass spectra were recorded on a Shimadzu GCMSꢀQP2010 Plus instrument in the
electron ionization (EI) mode, 70 eV, 200 °C via direct inlet probe. Only the molecular and
parent ions (m/z) are reported. IR spectra were recorded on a Bruker TENSOR 27 FT
instrument.
For the RX difraction studies, crystals of compound 9 were obtained by slow evaporation
of a dilute dichloromethaneꢀhexane solution, and the reflections were acquired with a
Bruker APEX DUO diffractometer equipped with an Apex II CCD detector, MoꢀKα
radiation (λ = 0.71073 Å) at 293 K. Three standard reflections every 97 reflections were
used to monitor the crystal stability. The structure was solved by direct methods; missing
atoms were found by differenceꢀFourier synthesis, and refined on F2 by a fullꢀmatrix leastꢀ
squares procedure using anisotropic displacement parameters using SHELXꢀ97.

Page 10 of 23
Computational Details
All gas phase DFT calculations were performed using the Gaussian 09 (Rev. D1) suite of
programs17 with the B3LYP functional18 and the 6ꢀ31G(d,p) basis set.19 Frequency analysis
were carried out at the same level of theory at the end of each geometry optimization to
verify that the corresponding structure was a local minima or a transition state, finding only
one imaginary frequency for the latter and none for the former. Transition states were
confirmed with intrinsic reaction coordinate (IRC) calculations to verify that the first order
saddle point connected the two local minima in each side of the potential energy surface.
Coordinates for all optimized structures as well as IRC paths are provided in the supporting
information.
Synthesis
of
4-Methyl-N-(1-phenylethyl)-N´-(1-phenylethylidene)
benzene
sulfonohydrazide (9). A solution of acetophenone pꢀtoluenesulfonylhydrazone (0.302 g,
1mmol), potassium tertꢀbutoxide (0.224 g, 2 mmol) and tetrabutylammonium iodide (0.01
g, 0.05 mmol) in anhydrous dioxane (5 mL) was stirred at 70 °C for 24 h. The mixture was
cooled at room temperature, H2O (15 mL) was added and the product was extracted with
CH2Cl2 (3 X 15 mL), the organic phases were joined and dried over Na2SO4, the solvent
was removed under reduced pressure and the product was purified by column
chromatography (SiO2, hexane/AcOEt 95:5) to afford a white solid (0.31 g, 80 %), m.p.
1
167ꢀ168°C (lit.166ꢀ168 ºC).6 FTꢀIR (ATR, cmꢀ1): 3030, 2992, 1590, 1365, 1183. H NMR
(300 MHz, CDCl3) δ 7.83 (d, J=8.4 Hz, 2H), 7.68 (d, J=8.4 Hz, 2H), 7.48 (t, J=8 Hz, 3H),
7.41 (t, J=7.5 Hz, 3H), 7.29ꢀ7.21 (m, 4H), 7.20ꢀ7.17 (m, 3H), 5.26 (q, J=7 Hz, 1H), 2.41 (s,
3H), 2.14 (s, 3H), 1.18 (d, J=7 Hz, 3H). 13C NMR (75MHz, CDCl3) δ 178.7 (C), 142.4

Page 11 of 23
(C), 139.8 (C), 136.3 (C), 134.0 (C), 129.8 (CH), 128.1 (2 X CH), 127.4 (2 X CH), 127.3 (2
X CH), 127.0 (2 X CH), 126.9 (2 X CH), 126.3 (CH), 126.2 (2 X CH), 59.4 (CH), 20.5
(CH3), 16.3(CH3), 14.2 (CH3). MS [EI+] m/z (%): 392 [M]+ (10), 91 [C7H7] (100).
Crystal data for 9: formula: C23H24N2O2S; FW 392.50; crystal system: Orthorhombic; space
group: P b c a; temp, K=296(2); λ, Å= 1.54178 Å; Unit cell dimensions a, Å= 14.6622(5);
b, Å=15.5860(5); c, Å=18.5481(6); α, deg=90; β, deg=90; γ, deg=90; V, Å3= 4238.7(2);
V=8; ρcalcld., g·cm–3=1.230; ꢁ, mm–1= 1.511; F(000)= 1664; crystal size, mm3=0.372 x
0.192 x 0.184; θ range for data collection, deg= 4.768 to 68.245; index ranges: ꢀ17 ≤ h ≤
17, ꢀ15 ≤ k ≤ 18, ꢀ15 ≤ l ≤ 22; Reflections collected: 23616; Independent reflections (Rint)=
3859 (0.0247); no. of data / restraints / parameters=3859 / 276 / 301; GoF on F2=1.035;
Final R indices [I>2σ(I)] R1 = 0.0407, wR2 = 0.1192; R1, wR2 (all data): 0.0468, 0.1257;
largest diff. peak / hole, e·Å–3=0.246 / ꢀ0.236.
Conversion
of
4-Methyl-N-(1-phenylethyl)-N´-(1-phenylethylidene)
benzene
sulfonohydrazide 9 into acetophenone azine 10. Method A. A solution of compound 9
(0.392g, 1 mmol), potassium tertꢀbutoxide (0.336 g, 3 mmol) in anhydrous dioxane (10
mL) was stirred at 70 °C for 48 h. The mixture was cooled at room temperature, H2O (15
mL) was added and the product was extracted with CH2Cl2 (3 X 15 mL), the organic phases
were joined and dried over Na2SO4, the solvent was removed under reduced pressure and
the product was purified by column chromatography (SiO2, hexane/AcOEt 95:5) to afford a
yellow solid (0.100 g, 85 %), m.p. 120ꢀ121°C (lit.120ꢀ121 ºC).20 FTꢀIR (ATR, cmꢀ1): 2919,
1
2888, 1605. H NMR (300 MHz, CDCl3) δ 7.88 (d, J=8.4 Hz, 4H), 7.40 (m, 6H), 2.29 (s,

Page 12 of 23
6H). 13C NMR (75MHz, CDCl3) δ 158.7 (C), 139.8 (C), 129.8 (CH), 128.1 (2 X CH), (2
X CH), 15.2 (CH3). MS [EI+] m/z (%): 236 [M]+ (80), 221 [M – CH3]+ (100).
Conversion
of
4-Methyl-N-(1-phenylethyl)-N´-(1-phenylethylidene)
benzene
sulfonohydrazide 9 into acetophenone azine 10. Method B. A suspension of compound 9
(0.392g, 1 mmol) SiO2 (2 g) in toluene (50 mL) was stirred at reflux temperature for 72 h.
The mixture was cooled at room temperature and the solvent was removed under reduced.
Purification by column chromatography (SiO2, hexane/AcOEt 95:5) afforded compound 5
as yellow solid (0. 0508 g, 43 %). Spectral characterization and other physical data matched
to those previously obtained in method A.
Acknowledgments
Financial support from CONACYT (Project No. 135053) is gratefully acknowledged. The
authors would like to thank Signa S.A. de C.V. for some graciously donated solvents and
reagents and to N. Zavala, A. Nuñez, L. Triana and M. C. Martínez for the technical
support.
References
1.ꢀ Fulton, J. R.; Aggarwal, V. K.; de Vicente, J. Eur. J. Org. Chem. 2005, 1479.
2.ꢀ Kirmse, W. in Carbene Chemistry, 2nd ed. Academic Press, New York, 1971, p. 415.
3.ꢀ Sharma, T. C.; Lal, A.; Saksena, V. Bull. Chem. Soc. Jpn. 1976, 49, 2881.
4.ꢀ Overberger, C. G.; Anseleme, J. P. I. J. Org. Chem. 1964, 29, 1188.
5.ꢀ Bethell, D.; Newall, A. R.; Stevens,G.; Whittaker, D. J. Chem. Soc. B, 1969, 749.
6.ꢀ Sha, Q.; Wei, Y. Tetrahedron, 2013, 69, 3829.

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7.ꢀ García, M. A.; GarcíaꢀMuñoz, A.; Peña, J. A.; TrujilloꢀReyes, J.; MoralesꢀLuckie, R.
A.; AvalosꢀBorja, M.; VilchisꢀNestor, A. R.; SánchezꢀMendieta, V.; Corona, D.; Cuevasꢀ
Yañez, E. Lett. Org. Chem. 2012, 9, 2.
8.ꢀ Alyar, S.; Adem, S. Spectrochim. Acta A, 2014, 131, 294.
9.ꢀ Hashemi, S. A. Tetrahedron Lett. 2012, 53, 5141.
10.ꢀ Yuan, Z. L.; Wei, Y.; Shi, M. Eur. J. Org. Chem. 2010,4088.
11.ꢀ Chen, Z. S.; Duan, X. H.; Wu, L. Y.; Ali, S.; Ji, K. G.; Zhou, P. X.; Liu, X. Y.; Liang,
Y. M. Chem. Eur. J. 2011, 17, 6918
12.ꢀ Yao, L.; Wang, C. J. Adv. Synth. Catal. 2015, 357, 384.
13.ꢀ Bethell, D.; Whittaker, D.; Callister; J, D. J. Chem. Soc. 1965, 2466.
14.ꢀ Bethell, D.; Whittaker, D. J. Chem. Soc. B 1966, 778.
15.ꢀ Hopkins, J. M.; Bowdridge, M.; Robertson, K. N.; Cameron, T. S.; Jenkins, H. A.;
Clyburne, J. A. C. J. Org. Chem. 2001, 66, 5713.
16.ꢀ Xu, X.; Zavalij, P. Y.; Doyle, M. P. Angew. Chem. Int. Ed. 2012, 51, 9829.
17.ꢀ Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.;
Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenb, D.
J. Gaussian 09, Revision D.01, 2009.
18.ꢀ Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
19.ꢀ Gill, P. M. W.; Johnson, B. G.; Pople, J. A.; Frisch, M. J. Chem. Phys. Lett. 1992, 197,
499.
20.ꢀ Lloyd, F. N.; Goodwin, T. C. J. Am. Chem. Soc. 1949, 71, 633.

Page 14 of 23
N N
N N
N N
N N
N N
6
O
HN S
:
3
Base
N N
N N
N N
O
N
5
1
2
4
O
N S
:
3
O
N
Base
7
Scheme 1. Mechanistic pathways on the formation of azine 5 from pꢀ
toluensulfonylhydrazone 1.

Page 15 of 23
O
HN S
tBuOK
nBu4NI
tBuOK
O
N
N N
S
N
O
O
N
or
SiO2
10
8
Dioxane,
70 ºC
9
Scheme 2. Synthesis of compound 9 and transformation to azine 10.

Page 16 of 23
Figure 1. ORTEP diagram and atom labelling system for compound 9.

Page 17 of 23
Table 1. Crystal data and structure refinement for the compound 9, C23H24N2O2S.
Crystal data
Empirical formula
Formula weight
Temperature
9
C23H24N2O2S
392.50
296(2) K
Wavelength
1.54178 Å
Crystal system
Space group
Orthorhombic
P b c a
Unit cell dimensions
a = 14.6622(5) Å
b = 15.5860(5) Å
c = 18.5481(6) Å
α
β
γ
= 90°.
= 90°.
= 90°.
Volume
3
4238.7(2) Å
8
Z
Density (calculated)
3
1.230 mg/m
Absorption coefficient
ꢀ1
1.511 mm
1664
F(000)
Crystal size
3
0.372 x 0.192 x 0.184 mm
4.768 to 68.245°
Theta range for data collection
Index ranges
ꢀ17<=h<=16, ꢀ18<=k<=18, ꢀ22<=l<=22
Reflections collected
Independent reflections
Data / restraints / parameters
23616
3859 [R(int) = 0.0247]
3859 / 276 / 301
1.035
2
Goodnessꢀofꢀfit on F
Final R indices [I > 2
R indices (all data)
R1 = 0.0407, wR2 = 0.1192
R1 = 0.0468, wR2 = 0.1257
0.06(3)
σ
(I)]
Absolute structure parameter
Largest diff. peak and hole
ꢀ3
0.246 / ꢀ0.236 (eÅ )

Page 18 of 23
Table 2. Selected bond distances (Å) and bond angles (deg) the compound 9,
C23H24N2O2S.
Bond
Distance (Å)
1.422(1)
1.423(1)
1.657(1)
1.756(2)
1.447(2)
1.502(2)
1.279(2)
Angle (°)
120.4(1)
108.6(1)
112.1(1)
110.3(1)
117.9(1)
114.1(1)
S(1)ꢀO(2)
S(1)ꢀO(1)
S(1)ꢀN(1)
S(1)ꢀC(17)
N(1)ꢀN(2)
N(1)ꢀC(1)
N(2)ꢀC(9)
Bond
O(2)ꢀS(1)ꢀO(1)
N(1)ꢀS(1)ꢀC(17)
N(2)ꢀN(1)ꢀC(1)
N(2)ꢀN(1)ꢀS(1)
C(1)ꢀN(1)ꢀS(1)
C(9)ꢀN(2)ꢀN(1)

Page 19 of 23
Figure 2. Crystal packing diagram of compound 1.

Page 20 of 23
Scheme 3. Studied reaction mechanisms for the formation of compound 5.

Page 21 of 23
Figure 4. Energy profiles for mechanisms 1, 2, and 3. Numbers are free energies relative to
the starting materials and are presented in kcal molꢀ1.

Page 22 of 23
Figure 5. Reaction profile and IRC path for mechanism 4. Relative energies to that of
starting materials are given in kcal molꢀ1.

Page 23 of 23
Figure 6. RMS gradient norm along the IRC path for mechanism 4. The dip in the curve
shows the presence of hidden intermediate 7.