Unexpected transalkylation on 3-alkyl-2-alkylthio-1,3,4-thiadiazolium-5- thiolates: A computational and experimental mechanistic study

Article abstract of DOI:10.1039/b923243e

5-Alkylthio-3-methyl-2-thioxo-1,3,4-thiadiazolines have been obtained on heating alkyl 1-methyl-1-hydrazinecarbodithioates with CS₂. A DFT-based computational mechanistic study suggests an initial pseudopericyclic [1,4]H shift as a key step, as well as the intermediacy of the otherwise expected isomers 2-alkylthio-3-methyl-1,3,4-thiadiazolium-5-thiolates, from which the final products are formed by stepwise S,S-transalkylation.

Full text of DOI:10.1039/b923243e

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Unexpected transalkylation on 3-alkyl-2-alkylthio-1,3,4-thiadiazolium-
5-thiolates: A computational and experimental mechanistic study†
Arturo Espinosa,* Rafaela Garc´ıa, Pedro Molina and Alberto Ta´rraga
Received 5th November 2009, Accepted 13th January 2010
First published as an Advance Article on the web 1st February 2010
DOI: 10.1039/b923243e
5-Alkylthio-3-methyl-2-thioxo-1,3,4-thiadiazolines have been obtained on heating alkyl
1-methyl-1-hydrazinecarbodithioates with CS2. A DFT-based computational mechanistic study
suggests an initial pseudopericyclic [1,4]H shift as a key step, as well as the intermediacy of the
otherwise expected isomers 2-alkylthio-3-methyl-1,3,4-thiadiazolium-5-thiolates, from which the final
products are formed by stepwise S,S-transalkylation.
thiadiazolium salt 4a (R = R¢ = Me). Conversely, on using an
alkyl halide as alkylating agent the nucleophilic soft counteranion
promoted the SC2-dealkylation furnishing alkylthio-thiadiazolin-
thiones 3. Such S-dealkylating behaviour had been also observed
in the reaction of 5-aryl substituted 3-methyl-2-methylthio-1,3,4-
thiadiazolium perchlorates with some O-nucleophiles2b and theo-
retically supported on the basis of quantitative Pearson’s HSAB
principle calculations.4
On the other hand, S-demethylation is a biochemically im-
portant reaction within methyl transfer metabolism,5 which has
been very recently studied theoretically.6 A well-established syn-
thetic S-demethylation reactivity was first found with inorganic
platinum(II) in 18837 and later with related halide compounds
of palladium(II) and gold(III), involving a transfer of the methyl
group from the metal to an external acceptor.8 In a wider context,
metal-induced S–C bond breaking constitutes an essential step in
the important technical process of hydrodesulfurization.9
In this paper we focus on the direct reaction of 1 with CS2, thus
avoiding the Kirsanov/aza-Wittig tandem reaction, with the hope
that the open-chain product 5a (X = Y = S) would be obtained
analogously than in the reported reactions involving isocyanates
or isothiocyanates (X = O, S; Y = NR¢¢) and carbodiimides
(X = Y = NR¢¢) (Scheme 1).2c The subsequent cyclization would
lead to either 5-mercapto-thiadiazolinthione 3 (R¢¢ = H) or
thiadiazolium-thiolate 2.
Introduction
The synthesis of compounds incorporating isolated or fused
1,3,4-thiadiazole rings has attracted widespread attention due to
their diverse pharmacological properties such as antiviral, antimi-
crobial, antiinflammatory, analgesic and antitumoral activities.1
Although there are a number of such compounds commercially
available for medical uses, the synthesis of new therapeutical
derivatives is of vital importance due to increasing drug resistance
and also looking for less toxic effects.
Based on our endeavors on the synthesis of 2-functionalized2
and 2,5-difunctionalized3 derivatives of the 1,3,4-thiadiazole ring
system we wanted to explore an easier access to 2,5-bisalkylthio-
3-methyl-1,3,4-thiadiazolium salts 4 as useful precursors for other
amino- or mercapto-substituted compounds. We reported3
a
synthetic strategy (Scheme 1) to obtain mesoionic thiadiazolium-
thiolate 2a (R = R¢ = Me) from the readily available methyl
1-methyl-1-hydrazinecarbodithioate 1a via the corresponding
iminophosphorane, whereas SC5-methylation of 2 with trimethy-
loxonium tetrafluoroborate yielded the expected bismethylthio-
Results and discussion
Alkyl 1-alkyl-1-hydrazinecarbodithioate 1, were easily prepared
according to the reported procedure,10 and were heated with
CS2 in a sealed tube to afford, in excellent yields (96–99%), the
corresponding 3-alkyl-5-alkylthio-2-thioxo-1,3,4-thiadiazolines 3
(Scheme 2) which were fully characterized spectroscopically (see
the ESI†). At lower temperatures or with shorter reaction periods
either the conversion decreased or the unaltered starting material
Scheme 1 Synthetic strategy to obtain compounds 2, 3 and 4.
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, Campus de
Espinardo, Universidad de Murcia, E-30100 Murcia, Spain. E-mail:
artuesp@um.es; Fax: +34 868 884149; Tel: +34 868 887489
† Electronic supplementary information (ESI) available: Structures, ener-
gies and lowest frequencies of all compounds cited in the text. NICSzz
variation along the reaction coordinate in steps involving TS1a–10 and
TS13syn–2a. See DOI: 10.1039/b923243e
Scheme 2 Synthesis of compounds 3.
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was only recovered. The isomeric nature of these products in
comparison with the expected thiadiazolium-thiolates 2 clearly
indicated that a transalkylation process must take place at any
of the individual steps in the overall transformation. This fact
prompted us to look for a detailed mechanistic scheme.
First, the relative stabilities of 2a and 3a were calculated using
the Gaussian03 package,11 and the Gibbs free energy change for
a hypothetical 2a→3a transformation resulted to be -16.35 or
-16.37 Kcal mol-1 at the B3LYP/6-311+G** or MP2/6-311+G**
levels of theory, respectively. This indicates that 3 could be formed
as a thermodynamic control product if 2 was involved as an
intermediate in the process. In order to check this possibility,
samples of 2a were heated in either CS2 or toluene and quantitative
conversion in 3a was observed in both cases.
A thorough inspection of all possible paths connecting 1a and
3a in the potential energy surface at the B3LYP/6-311+G** level
revealed that actually all reasonable low-energy paths required
the intermediacy of 2a, thus excluding the possibility of a
transalkylation taking place on any of the open-chain precursors
and pointing to a final transalkylation step.
The obtained energy paths are depicted in Fig. 1, which shows
Scheme 3 Paths A and B.
that formation of 2a is an endergonic process (DG◦2a = 10.55 Kcal
mol-1), but formation of the final product 3a is exergonic (DG◦
=
3a
-2.14 Kcal mol-1). The expected direct nucleophilic attack of 1a
to CS2 was observed to proceed from the anti rotamer of 1a,
affording intermediate 6 (Fig. 1, path A) (Scheme 3). Compound
6 can then undergo ring-closure to 7, which is also formed
following a lower energy path through tautomer 8, and readily
undergoes dehydrosulfurization to mesoionic compound 2a. On
the contrary, the most stable 1asyn conformer behaves exclusively
as S-nucleophile towards carbon disulfide (no path was found for
the N-attack to CS2). This process requires concomitant N,S-
prototropy to yield betaine 9 (path B). Nevertheless no path
was found connecting this intermediate to final products 2a or
3a. Thermochemical data corresponding to every single step are
collected in Table 1.
Both pathways (A and B) for the direct nucleophilic attack of 1a
to CS2 involve rather high energetic barriers (53.78 and 57.44 Kcal
mol-1, respectively).
Instead of that, previous formation of the “pseudo-valence”
isomer 10 (Scheme 4)—very much resembling the structure of
intermediate 9—seems to be required, as it proceeds through a
much lower energetic barrier (Table 1). Betaine 10 reacts with
CS2 via the highly nucleophilic terminal N atom affording 11.
From this easily accessible key intermediate 11 several low energy
paths are possible. First, cyclization of 11 (Scheme 4, path C1)
by the action of its highly nucleophilic S atom affords 12, from
which 2a is easily formed by dehydrosulfurization. An analogous
route (path C2) can be followed after conversion 11→13 by N,S-
prototropy followed by cyclization (14) and dehydrosulfurization.
This later precursor 14 can also be obtained by N,S-prototropy of
thiadiazolidine 12, preferably in a intermolecular fashion. Finally,
dehydrosulfurization of 13 yields isothiocyanate 15anti (path D)
that easily undergoes pseudopericyclic cyclization to its valence
tautomer 2a. This last step is controlled by the rotation around the
N–N bond (15anti→15syn) through a rather small energetic barrier,
whereas the cyclization of 15syn resulted to be an almost barrierless
process (DG◦ = 0.02 Kcal mol-1 in the gas-phase). Indeed
TS
intermediate 15syn does not exist as such local energy minimum in
other lower level potential energy surfaces (i.e. B3LYP/6-31+G*).
Although path C2 constitutes the lowest energy access to 2a, it
is important to underline that all steps following intermediate 11
have lower activation energies than formation of the precursor 10
and therefore all three are actually competing pathways.
Fig. 1 Calculated (COSMO[CS2]/B3LYP/6-311+G**) energy paths and activation free energies (Kcal mol-1) for the conversion 1a→3a: A) blue/green,
B) red, C) black, D) grey.
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Table 1 Thermochemical dataa for reactions depicted in Schemes 3
molecule of 2a by means of a nucleophilic attack of the thiolate
S-atom of another identical molecule affording the ion-pair 16
(Scheme 4). The thiolate S-atom in 16 again S-dealkylates the
methylthio group at C-2 of the cation, furnishing two identical
molecules of 3a. This later step is analogous to the above
mentioned S-demethylation of 4 by the action of soft counter-
anions.3
A direct one-step transformation 2a→3a through a bimolecular
mechanism (two simultaneous S,S-trans-methylations) would
probably compete as it requires only a slightly higher activation
energy (see the ESI†) due to the unfavourable entropic contribu-
tion. This species is indeed a second-order saddle point with two
imaginary frequencies, one related with the required Ci-symmetric
vibration (-358.0 cm-1) that corresponds to the aforementioned
2a→3a transformation (Scheme 5), and having also a second
asymmetric vibration (-511.6 cm-1) associated to a degenerated
double transmethylation 16→16. An alternative unimolecular
mechanism for the 2a→3a isomerization could also be envisaged
involving a pericyclic (six p-electrons) migration of a methyl group
from N-3 to N-4 over all the dienic heterocyclic ring, but according
to our calculations this constitutes a nearly energetically forbidden
process (Table 1).
and 4
Reaction
DG◦
DGTS
1asyn→1aanti
1aanti→6
6→7
0.75
16.13
53.78
49.94
34.18
20.28
5.49
57.44
31.91b
38.71c
20.91
1.95
16.49
28.62
9.35
19.27
-35.31
52.56
31.40
6→8
8→7
7→2a
1asyn→9
1asyn→10
10→11
11→12
12→2a
11→13
12→14
6.94
-7.77
-20.02
-5.81
2.11
23.18
21.22
36.71b
10.80c
12.10
16.15
24.70
3.80
13→14
0.15
14→2a
-22.14
-13.80
-1.52
-6.67
4.95
-17.64
-12.70
13→15anti
15anti→15syn
15syn→2a
-0.54d
9.32
1
2
2a→ 16
12 16→3a
2a→3a
3.78
63.81b
24.14c
a Kcal·mol-1; b unimolecular; c bimolecular; d 0.02 Kcal·mol-1 in the gas-
phase
Scheme 5 Representations of one-step TS2a–3a structures.
In order to confirm the bimolecular nature of the final transalky-
lation process, a crossed experiment was performed by heating
equimolecular amounts of two different alkyl dithiocarbazates 1a
and 1d in carbon disulfide, according to the reaction depicted
in Scheme 2. After completion and evaporation of the excess of
solvent, the composition of the reaction mixture was analyzed
by GC-MS (see the ESI†) resulting in roughly equal amounts of
all the four possible reaction products 3a (30.5%), 3b (22.2%), 3c
(24.4%) and 3d (22.9%).
It is worth mentioning that the initial prototropy 1a→10
corresponds to the rate-determining step of the overall process
when following the proposed path, thus explaining that no
intermediate has ever been isolated.
Finally, conversion 1a→10 constitutes, to the best of our
knowledge, the first example of a 6-electrons pseudopericyclic
[1,4]H N-to-S rearrangement. At first sight, the pseudopericyclic
nature of TS1a–10 is evidenced not only by the very low energetic
barrier (DGTS = 0.50 Kcal mol-1 for the reverse transformation
10→1a) but also by the almost planar geometry of the transition
state (TS1a–10) featuring a characteristic orbital topology with two
orbital disconnections (Fig. 2, left).12 The alternative bimolecular
N,S-prototropy has been also checked and seems to constitute
a competitive pathway according to its only slightly higher
activation energy (Table 1).
Scheme 4 Paths C and D.
Once the thiadiazolium-thiolate 2a has been formed, the
isomerization to 3a is predicted to take place through a stepwise
bimolecular mechanism involving the initial S-dealkylation of one
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shown to be the unprecedent initial [1,4]H N-to-S rearrangement
of the hydrazinecarbodithioate reagent, whose pseudopericyclic
nature was unambiguously established.
Experimental section
Melting points were determined on a hot-plate melting point
apparatus and are uncorrected. IR spectra were determined as
Nujol emulsions. 1H- and 13C-NMR spectra were recorded at
300 and 75 MHz, respectively. Chemical shifts refer to signals
of tetramethylsilane. The following abbreviations for stating the
multiplicity of the signals have been used: s (singlet), d (doublet),
m (multiplet), q (quaternary carbon). The EI mass spectra were
recorded on a Fisons AUTOSPEC 500 VG spectrometer. The
coupled GC-MS experiment was performed with 6890 N and 5973
N subunits, fitted with an Agilent 19091S-433 HP-5MS column,
and using heli◦um (1mL min-1) as carrier an◦d a temperature profile
starting at 60 C (1 min) and warming (10 C min-1) up to 310 ◦C
(10 min). Microanalyses were performed on a Carlo Erba 1108
instrument.
Fig. 2 Calculated NICS values along the perpendicular z axis for TS1a–10
), TS15syn–2a ) and TS17–17 ). Schematic representation of the
pseudopericyclic orbital topology in TS1a–10 (left) and TS15syn–2a (right).
(
(
(
A deeper insight into the pseudopericyclic character of both
TS1a–10 and TS15syn–2a comes from the observation of the almost
symmetric NICS distribution along the perpendicular z axis
(Fig. 2), which is consistent with the expected s-aromaticity
of such flat TS structures.13 Their highest negative values (c.a.
˚
-7.3 ppm, at z = 0 A) are significantly smaller than that calculated
for the TS corresponding to a genuine symmetry-allowed pericyclic
[1,4]H shift in Z-2-butenyl anion (17). In this case, the NICS
variation for TS17–17 along the z axis shows an asymmetric pattern
Computational details
1
attributable to the p -aromaticity behaviour that results, in a
Calculated geometries were fully optimized in the gas-phase with
tight convergence criteria at the DFT level with the Gaussian
03 package,11 using the B3LYP17 functional and the 6-311+G**
basis set for all atoms, unless otherwise stated. Ultrafine grids (99
radial shells and 590 angular points per shell) were employed for
numerical integrations. From these gas-phase optimized geome-
tries all reported data were obtained by means of single-point
(SP) calculations. Frequency calculations confirmed the nature of
ground states and transition states by the existence of none or only
one imaginary vibration mode, respectively. Reported electronic
energies are uncorrected for the ZPVE (zero-point vibrational
energy). Solvent effects were considered by using the Cossi and
Barone’s CPCM (conductor-like polarizable continuum model)
modification18 of the Tomasi’s PCM formalism.19 With this aim
carbon tetrachloride was used as the most similar solvent to CS2,
among those available in Gaussian03, but correcting with available
data for CS2: the dielectric constant was set to 2.2 and the solvent
formal sense, from only one ring current circulating on the side
where the H atom movement allows a close proximity between the
terminal p atomic orbitals.
Also the NICS(0) and NICS(1)14 variation along the reaction
coordinates 1a→10 and 15syn→2a (Fig. 3) agrees with the classi-
fication of these steps as pseudopericyclic,15 specially for the later
where only an smooth maximum is observed for -NICS(0), but
far away from the coordinate corresponding to the TS (dC ◊ ◊ ◊ S
=
˚
2.488 A). On the contrary, the 1a→10 prototropy shows small but
not negligible maxima for both NICS(0) and NICS(1) close to
˚
the transition state coordinate (dN ◊ ◊ ◊ H = 1.614 A), which indicate
an aromaticity enhancement and thus pointing to some pericyclic
character. Similar results were obtained on using the out-of-plane
component of the magnetic shielding tensor (NICSzz) (see the ESI)
which is reported as a better aromaticity index.16
˚
radius to 3.40 A. The only structure that could not be localised at
the working level of theory was that of TS10-11, for which the fully
optimized structure obtained by using the 6-31+G* basis set was
employed, although the energy (excepting the thermal correction
to the Gibbs free energy) was computed as SP calculation at the
final B3LYP/6-311+G** level of theory. Values from the magnetic
shielding tensor were obtained using the non-relativistic gauge-
including atomic orbital (GIAO) approach.20 Additionally, the
structures of compounds 2a and 3a (as well as carbon disulfide)
were also further refined at the MP221 level of theory with the
6-311+G** basis set.
Fig. 3 Calculated NICS values variation along the reaction coordinate
for steps 1a→10 (a) and 15syn→2a (b): NICS(0) (
); NICS(1) (
).
Alkyl 2-Alkyldithiocarbazes 1 prepared
Compounds 1 were prepared according to the reported10 proce-
dure. In common solvents these compounds exhibit a hindered
rotation around the N-CS bond giving rise to the appearance of
the signals belonging to both rotamers in their NMR spectra.
Herein only those signals corresponding to the major rotamer are
collected.
Conclusions
We report an efficient synthesis of 5-alkylthio-1,3,4-thiadiazolin-
2-thiones that, according to DFT calculations, involves an in-
termolecular double S,S-transalkylation in the intermediately
formed thiadiazolium-thiolate isomer. The key step has been
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1a. Colorless prisms, m.p. 94–95 ◦C (lit.,10 92 ◦C).
125 (43), 91 (100). Anal Calcd for C16H13N2S3Cl: C, 52.66; H, 3.60;
N, 7.67; S, 26.36. Found: C, 52.96; H, 3.63; N, 7.45; S, 26.60.
1b. White prisms, m.p. 61–62 ◦C. IR (nujol) nmax: 3297, 1225,
1
H
1090, 842 cm-1. H NMR (CDCl3) d (ppm): 7.32 (d, 2H, J =
Crossed experiment for the synthesis of
3-alkyl-5-alkylthio-2-thioxo-1,3,4-thiadiazolines 3
8.47 Hz), 7.27 (d, 2H, J = 8.47 Hz), 4.27 (s, 2H, S-CH2), 3.84
(s, 3H, N-CH3), 3.73 (s, 2H, NH2). 13C NMR (CDCl3) d (ppm):
C
=
200.3 (C S), 134.1 (q), 133.6 (q), 130.6 (CH), 129.0 (CH), 38.8
A
suspension of equimolecular amounts of methyl 2-
(S-CH2), 36.9 (N-CH3). MS (EI): m/z (%): 246 (M+, 7), 127 (35),
125 (100), 89 (35). Anal Calcd for C9H11N2S2Cl: C, 43.80; H, 4.49;
N, 11.35; S, 25.99. Found: C, 43.45; H, 4.31; N, 11.06; S, 26.39.
methyldithiocarbazate 1a (5 mmol) and 4-chlorobencyl 2-
benzyldithiocarbazate 1d (5 mmol) in carbon disulfide (10 mL)
is heated at 125 ◦C for 48 h. On cooling, the mixture is evaporated
to dryness and the resulting solid is submitted to GC-MS analysis.
1c. White needles, m.p. 92–93 ◦C. IR (nujol) nmax: 3275,
H
1224 cm-1. 1H NMR (CD3CN) d (ppm): 7.21–7.01 (m, 5H), 5.20
(s, 2H, N-CH2), 4.26 (s, 2H, NH2), 1.92 (s, 3H, S-CH3). 13C NMR
Acknowledgements
C
=
(CD3CN) d (ppm): 200.1 (C S), 136.6 (q), 130.1 (CH), 129.5
We gratefully thank the grants from MICINN-Spain, Project
CTQ2008-01402 and Fundacio´n Se´neca project 04509/
GERM/06 (Programa de Ayudas a Grupos de Excelencia de
la Regio´n de Murcia, Plan Regional de Ciencia y Tecnolog´ıa
2007/2010).
(CH), 129.2 (CH), 61.0 (N-CH2), 20.5 (S-CH3). MS (EI): m/z
(%): 213 (M++1, 6), 121 (36), 91 (100). Anal Calcd for C9H12N2S2:
C, 50.91; H, 5.70; N, 13.19; S 30.20. Found: C, 50.85; H, 5.70; N,
13.07; S, 30.53.
1d. White prisms, m.p. 109–110 ◦C. IR (nujol) nmax: 3302, 1222,
H
1089, 854 cm-1. 1H NMR (CD3CN) d (ppm): 7.46–7.24 (m, 9H),
Notes and references
5.40 (s, 2H, N-CH2), 4.54 (s, 2H, NH2), 4.38 (s, 2H, S-CH2). 13
C
C
1 (a) V. S. Misra and N. S. Agarwal, J. Prakt. Chem., 1969, 311, 697;
(b) L. F. Awad and S. H. El Ashry, Carbohydr. Res., 1998, 312, 9;
(c) A. Varvaresou, T. Siatra-Papastaikoudi, A. Tsantili-Kakoulidou and
A. Vamvakides, Farmaco, 1998, 53, 320; (d) E. Palaska, G. Sahin, P.
Kelicen, N. T. Durlu and G. Altinok, Farmaco, 2002, 57, 101; (e) B. S.
Holla, K. N. Poorjary, B. S. Rao and M. K. Shivananda, Eur. J. Med.
Chem., 2002, 37, 511; (f) M. Amir and K. Shikha, Eur. J. Med. Chem.,
2004, 39, 535; (g) N. Demirbas, S. Alpay Karaoglu, A. Demirbas
and A. Sancak, Eur. J. Med. Chem., 2004, 39, 793; (h) S. Schenone,
C. Brullo, O. Bruno, F. Bondavalli, A. Ranise, W. Filippelli, B.
Rinaldi, A. Capuano and G. Falcone, Bioorg. Med. Chem., 2006, 14,
1698; (i) A.-R. Farghaly, E. De Clercq and H. El-Kashef, Arkivoc,
2006, (x), 137; (j) A. O. Abdelhamid and A. R. Sayed, Phosphorus,
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2 (a) P. Molina, A. Ta´rraga and A. Espinosa, Synthesis, 1988, 690; (b) P.
Molina, A. Ta´rraga and A. Espinosa, Heterocycles, 1989, 29, 2301;
(c) P. Molina, A. Ta´rraga and A. Espinosa, Synthesis, 1989, 923; (d) P.
Molina, A. Ta´rraga, I. D´ıaz, A. Espinosa and C. Gaspar, Heterocycles,
1993, 36, 1263; (e) P. Molina, A. Ta´rraga, C. Gaspar and A. Espinosa,
J. Org. Chem., 1994, 59, 3665.
=
NMR (CD3CN) d (ppm): 200.2 (C S), 136.5 (q), 134.7 (q), 131.9
(q), 130.5 (CH), 128.5 (CH), 127.9 (CH), 127.6 (CH), 59.4 (N-
CH2), 39.5 (S-CH2). MS (EI): m/z (%): 197 (7), 159 (17), 157
(50), 148 (29), 127 (25), 125 (77), 121 (52), 91 (100). Anal Calcd
for C15H15N2S2Cl: C, 55.80; H, 4.68; N, 8.68; S 19.86. Found: C,
55.62; H, 4.70; N, 8.87; S 19.94.
General procedure for the synthesis of
3-alkyl-5-alkylthio-2-thioxo-1,3,4-thiadiazolines 3
A suspension of the appropiate alkyl 2-alkyldithiocarbazate 1
(10 mmol) in carbon disulfide (10 mL) is heated at 120 ◦C for 24 h.
On cooling, the mixture is evaporated to dryness and the resulting
solid is scratched with hexane, filtered off and crystallized from
ethanol.
3a. Yellow needles, m.p. 83–84 ◦C (lit.,3 84 ◦C).
3 P. Molina, A. Espinosa, A. Ta´rraga, F. Herna´ndez-Cano and M. C.
Foces-Foces, J. Chem. Soc., Perkin Trans. 1, 1991, 1159.
4 A. Espinosa, A. Frontera, R. Garc´ıa, M. A. Soler and A. Ta´rraga,
Arkivoc, 2005, (ix), 415.
5 L. Stryer, Biochemistry, 4th ed., Freeman: New York, 1995,
p 722.
◦
3b. Pale yellow prisms, m.p. 62–63 C. IR (nujol) nmax: 1596,
1258, 1091, 833 cm-1. H NMR (CDCl3) d (ppm): 7.24 (s, 4H),
1
H
4.21 (s, 2H, S-CH2), 3.77 (s, 3H, N-CH3). 13C NMR (CDCl3) d
C
(ppm): 185.6 (C2), 154.2 (C5), 134.2 (q), 133.6 (q), 130.1 (CH),
129.0 (CH), 38.8 (N-CH3), 37.0 (S-CH2). MS (EI): m/z (%): 290
(M++2, 8), 288 (M+, 17), 159 (2), 157 (6), 127 (39), 125 (100), 73
(11). Anal Calcd for C10H9N2S3Cl: C, 41.58; H, 3.14; N, 9.70; S,
33.30. Found: C, 41.30; H, 3.07; N, 9.69; S, 33.10.
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8 For a review see:S. G. Murray and F. R. Hartley, Chem. Rev., 1981, 81,
365.
3c. Yellow oil. IR (nujol) nmax: 1604, 1186 cm-1. H NMR
1
9 (a) T. Weber, R. Prins, and R. A. van Santen, (ed.) Transition
Metal Sulfides; Kluwer: Dordrecht, The Netherlands, 1998; (b) T.
Kabe, A. Ishihara, and W. Quian, Hydrodesulfurization and Hy-
drodenitrogenation; Wiley-VCH: New York, 2000; (c) R. Sa´nchez-
Delgado, Organometallic Modelling of the Hydrodesulfurization and
Hydrodenitrogenation Reactions; Springer-Verlag: Berlin, 2002.
10 (a) M. A. Ali, S. E. Livingstone and D. J. Phillips, Inorg. Chim. Acta,
1972, 6, 11; (b) M. A. Ali and S. C. Teoh, J. Inorg. Nucl. Chem., 1978,
40, 451.
11 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C.
Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci,
M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M.
Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E.
Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
H
(CDCl3) d (ppm): 7.38–7.32 (m, 2H), 7.29–7.21 (m, 3H), 5.36 (s,
2H, N-CH2), 2.50 (s, 3H, S-CH3) 13C NMR (CDCl3) d (ppm):
C
185.4 (C2), 156.4 (C5), 134.6 (q), 128.7 (CH), 128.5 (CH), 128.2
(CH), 53.9 (N-CH2), 15.4 (S-CH3). MS (EI): m/z (%): 254 (M+,
18), 181 (3), 149 (6), 148 (81), 91 (100). Anal Calcd for C10H10N2S3:
C, 47.21; H, 3.96; N, 11.01; S, 37.81. Found: C, 47.34; H, 3.96; N,
11.32; S, 38.07.
◦
3d. White flakes, m.p. 75–76 C. IR (nujol) nmax: 3303, 1601,
1221, 1089, 854 cm-1. 1H NMR (CDCl3) d (ppm): 7.40–7.23 (m,
H
9H), 5.45 (s, 2H, N-CH2), 4.40 (s, 2H, S-CH2). MS (EI): m/z (%):
366 (M++2, 0.5), 364 (M+, 2), 159 (2), 157 (7), 148 (9), 127 (12),
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