Reactions of 1,2,5-thiadiazole 1,1-dioxide derivatives with nitrogen nucleophiles. Part IV. Addition of α-diamines

Article abstract of DOI:10.1002/poc.1444

α-diamines, such as ethylendiamine and o-phenylendiamine, add to 3,4-aryl-disubstituted 1,2,5-thiadiazole 1,1-dioxides to give dihydropyrazines or quinoxalines, respectively and sulfamide. The new compound acenaphtho [5,6-b]-2,3-dihydropyrazine was synthesized and characterized. The addition of ethylendiamine to 3,4-diphenyl-1,2,5-thiadiazoline 1,1-dioxide gives 3,4-disubstituted thiadiazolidlne 1,1-dioxide, dihydropyrazines, or pyrazines, depending on the reaction condition used. The reactions were followed by cyclic voltammetry and NMR spectroscopy which, in some cases, allowed the detection of the thiadiazolidine intermediate. Copyright

Full text of DOI:10.1002/poc.1444

Research Article
Received: 18 April 2008,
Revised: 12 August 2008,
Accepted: 12 August 2008,
Published online in Wiley InterScience: 24 September 2008
(www.interscience.wiley.com) DOI 10.1002/poc.1444
Reactions of 1,2,5-thiadiazole 1,1-dioxide
derivatives with nitrogen nucleophiles.
Part IV. Addition of a-diamines
ay
ay
Marı´a Virginia Mirı´ficoa,b ,y, Jose Alberto Caram , Enrique Julio Vasini ,
*
´
Oscar Enrique Pirocy and Eduardo E. Castellanody
a-diamines, such as ethylendiamine and o-phenylendiamine, add to 3,4-aryl-disubstituted 1,2,5-thiadiazole
1,1-dioxides to give dihydropyrazines or quinoxalines, respectively and sulfamide. The new compound acenaphtho
[5,6-b]-2,3-dihydropyrazine was synthesized and characterized. The addition of ethylendiamine to 3,4-diphenyl-
1,2,5-thiadiazoline 1,1-dioxide gives 3,4-disubstituted thiadiazolidine 1,1-dioxide, dihydropyrazines, or pyrazines,
depending on the reaction condition used. The reactions were followed by cyclic voltammetry and NMR spectroscopy
which, in some cases, allowed the detection of the thiadiazolidine intermediate. Copyright ß 2008 John Wiley &
Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: thiadiazoles; nucleophilic addition; a-diamines; dihydropyrazines; pyrazines; quinoxalines
INTRODUCTION
EXPERIMENTAL
We have reported that several organic nucleophiles (alcohols,
thiols, aromatic monoamines, and N-unsubstituted monocarbox-
Compounds 1a, b, c, and 2a were synthesized, purified, and
characterized according to the literature.[5,13] Standard methods
were used for the purification of commercial (p.a. grade) solvents
and amines.[14–16] Purified solvents were further dried with
freshly activated 4A molecular sieves and stored under a dry
nitrogen atmosphere in a glove box. Their water content was
50 ppm or lower, as measured by Karl-Fischer coulometric
titration.
amides), in aprotic solvent (MeCN, DMF, DMSO) solution,[1–6] add
—
to only one of the two C N double bonds of 1 (Scheme 1) in an
—
equilibrium reaction. This decreased reactivity of the remaining
double bond has also been observed with Grignard reagents.[7]
Our work on the molecular structure of these compounds
(single-crystal X-ray diffraction and theoretical calculations)
allowed us to rationalize this behavior.[8]
However, di-addition products are obtained in the reactions of
1 with bifunctional, nitrogen nucleophiles of similar strength,
such as unsubstituted, mono- and symmetrically disubstituted
*
Correspondence to: M. V. Mir´ıfico, INIFTA C.C. 16, Suc. 4 (1900) La Plata,
Argentina.
E-mail: mirifi@inifta.unlp.edu.ar
—
ureas, and thioureas, which add to both C N double bonds
—
yielding bicyclic thiadiazolidine compounds (Fig. 1). The stability
acquired by cycle formation and the intramolecular character of
the second addition might justify the increased reactivity.[6,9]
With stronger organic nucleophiles (aliphatic primary mono-
amines and phenylhydrazine), double addition and sulfamide
displacement takes place to give a-bis-imines and
a-bis-hydrazone, respectively (Fig. 2).[10]
We report in this work the results of our studies on the reactions
of several derivatives of 1,2,5-thiadiazole 1,1-dioxide (Scheme 1):
3,4-diphenyl- (1a), phenanthro [9,10-c]- (1b) and acenaphtho
[1,2-c]- (1c) 1,2,5-thiadiazole 1,1-dioxide and 3,4-diphenyl- 1,2,5-
thiadiazoline 1,1-dioxide (2a), with o-phenylenediamine (o-PDA)
and ethylenediamine (EDA) to give the corresponding quinox-
alines, dihydropyrazines, and pyrazines.
a
M. V. Mir´ıfico, J. A. Caram, E. J. Vasini
´
Instituto de Investigaciones Fisicoqu´ımicas Teoricas y Aplicadas (INIFTA),
Facultad de Ciencias Exactas, Departamento de Qu´ımica, Universidad
Nacional de La Plata, Casilla de Correo 16, Sucursal 4, (1900) La Plata,
Argentina
b
c
M. V. Mir´ıfico
Facultad de Ingenier´ıa, Departamento de Ingenier´ıa Qu´ımica, Universidad
Nacional de La Plata, Calle 47 y 1, (1900) La Plata, Argentina
O. E. Piro
Departamento de F´ısica, Facultad de Ciencias Exactas, Universidad Nacional
de La Plata and IFLP (CONICET), C. C. 67, 1900 La Plata, Argentina
d
E. E. Castellano
˜
Instituto F´ısica de Sao Carlos, Universidade de Sao Paulo, C.P. 369, 13560 Sao
˜
˜
The main reactants and products discussed in this work are
summarized in Scheme 1.
Carlos (SP), Brazil
y
The course of the reactions was followed by cyclic voltammetry
(CV)[11] and NMR spectroscopy.
MVM, JAC, and EJV have had equal participation in the realization of this work.
OEP and EEC had measured and analyzed the single crystal X-ray.
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´
M. V. MIRIFICO ET AL.
Scheme 1. Structures of the main reactants and products discussed in this work
1H and 13C NMR spectra were measured with a Brucker
200 MHz instrument and IR spectra with a Shimadzu IR-435
spectrophotometer (KBr disk).
Synthesis of compounds
Quinoxalines
The CV experiments were performed in a conventional
undivided gas-tight glass cell with dry nitrogen gas inlet and
outlet. The working electrode was a 3 mm diameter vitreous
carbon disk encapsulated in Teflon, the counter-electrode was a
2 cm2 Pt foil. A Agþ (0.1 M, MeCN)/Ag reference electrode (to
which all potentials reported are referred) was used. The
supporting electrolyte was NaClO4. A LYP-M2 potentiostat, a
3-module LYP sweep generator, and a Houston Omnigraphic
2000 pen recorder were used. Since sulfamide is one of the
products in most of the reactions studied in this work, it was
always added to the control CVs scanned for product
identification purposes. The CVs scans with added sulfamide
are shown only in the cases in which its addition caused changes
in the CV of the control substance.
Quinoxalines were obtained in high yield by a general procedure,
exemplified here for 2,3-diphenylquinoxaline (3a): 1a (134 mg,
0.496 mmol) and o-PDA (227 mg, 2.10 mmol) were added to the
DMF solvent (1 ml). The solution was left to stand overnight at
room temperature. A precipitate was obtained upon addition of
water (5 ml). The precipitated was filtered, washed thoroughly
with water, dried at reduced pressure at 25 8C and recrystallized
(ethanol-water) at r.t. to give 107 mg (0.379 mmol; 76% yield) of
the chromatographically (TLC) pure solid 3a; mp 122.0–123.0 8C
(Lit[17]: 124 8C). Its IR spectrum was identical to that reported.[18]
Sulfamide was found in the mother liquors.
Dibenzo(a,c)phenazine (3b) was obtained by the same
procedure through the mixture of similar molar proportions of
1b and o-PDA. 3b (mp 213.0–215.0 8C; Lit[17]: 217 8C) was
obtained in 97% yield, and was identified by comparison (TLC,
mixture mp, IR) with an authentic sample obtained according to a
standard synthesis procedure.[17]
Solution preparation, synthesis reactions, and CV experiments
were made in a glove box under a dry nitrogen atmosphere at
room temperature (ca 20 8C).
Dihydropyrazines and pyrazines
5,6-diphenyl-2,3-dihydropyrazine (4a) from 1a: 1a (145 mg,
0.537 mmol) and EDA (33.0 mg, 0.549 mmol) were added to
the DMF solvent (2 ml). The precipitate obtained after a few
minutes at r.t. was filtered. Water (5 ml) was added to the liquid
filtrate and a new portion of the same solid (TLC) was obtained.
Both solid combined were washed thoroughly with water and
dried at reduced pressure at 25 8C. The pure (TLC) solid obtained
was identified as 4a (110 mg; 0.469 mmol; 87% yield) by IR
Figure 1. Stable products of the addition of mono- and symmetrically
—
disubstituted ureas and thioureas to both C N double bonds of 1
(Ar¼Ph)
Figure 2. a-bis-imines and a-bis-hydrazone products of the diaddition
reaction of aliphatic primary monoamines and pheylhydrazine
—
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a-DIAMINES ADDITION TO THIADIAZOLE DERIVATIVES
spectrum[19] and melting point (160.4–165.0 8C; Lit:163–
165 8C[20]; 162.5–163.5 8C[21,22]).
5,6-diphenyl-2,3-dihydropyrazine (4a) from 2a: 2a (239 mg
0.88 mmol) and EDA (112 mg, 1.86 mmol) were added to the
DMF solvent (0.53 ml) and left at r.t. for 22 days. The solvent was
vacuum rota-evaporated and the orange colored solid obtained
was extracted with cyclohexane (20 ml). The remaining solid was
dissolved in MeCN/benzene (1:1, 5 ml). The solution was cooled
to ꢀ5 8C and an oily, orange colored liquid separated. The
solution was evaporated to near dryness, and a yellow precipitate
was obtained. A similar solid was obtained by rota-evaporation
of the extracting cyclohexane solution to a ca. 1 ml final
volume. Both solids reunited were recrystalized from ethanol-
cyclohexane (1:3). The crystals (115 mg, 0.490 mmol, 56% yield)
were identified as 4a as above.
2,3-diphenylpyrazine: 4a (87 mg; 0.37 mmol) and EDA (24 mg;
0.40 mmol) were dissolved in DMF (1 ml) and left to stand at r.t. for
a month. The solvent was vacuum rota-evaporated at 40 8C. The
remaining crystalline solid (56 mg, 0.33 mmol) was filtered and
dried. It was identified as 2,3-diphenylpyrazine (yield: 89%) from
its IR spectrum.[23]
Phenanthro [9,10-b]-2,3-dihydropyrazine (4b): This compound
was identified by NMR spectroscopy in a solution of 1b (37.0 mg,
0.138 mmol) and EDA (10.0 mg, 0.166 mmol) in CDCl3 (0.7 ml)
freshly prepared. 4b dehydrogenates upon work-up yielding the
corresponding pyrazine, which was identified by its reported IR
spectrum.[24]
1H NMR (d, TMS) in CDCl3: 8.26–7.34 (multiplet, CArom—H, 8H),
[25]
3.74 (singlet, >CH2, 4H).
C NMR (d, TMS) same solution: 153.8 (—C N), 133.4–123.5
(six signals, CAr), 44.9 (heterocyclic sp3 C-atoms).
Figure 3. Ortep Diagram
of 4c showing the labeling of the non-H
13
—
—
atoms and their displacement ellipsoids at the 50% probability level. The
plot includes a crystallization water solvent molecule
Acenaphtho [5,6-b]-2,3-dihydropyrazine (4c): 1c (420 mg;
1.73 mmol) and EDA (134 mg; 2.23 mmol) were dissolved in
MeCN (15 ml). The dark brown precipitate obtained after a few
minutes at r.t. was filtered and washed with ethanol and dried at
reduced pressure at 25 8C (78 mg, solid A). The solvent was
evaporated from the remaining solution at reduced pressure at
r.t., and CHCl3 (20 ml) was added to the resulting residue. An
off-white solid remained undissolved and was identified by its IR
spectrum as sulfamide (125 mg, 1.30 mmol). The chloroformic
solution was decolorized with activated charcoal. Evaporation of
the CHCl3 solvent produced a dark orange solid (223 mg), which
was found to be identical (TLC, IR) to solid A. Both solids,
combined and recrystallized from ethanol/water (1:3) yielded
acenaphtho [5,6-b]-2,3-dihydropyrazine (180 mg; 0.873 mmol;
44%), mp 143.0–144.0 8C. The single crystal X-ray analysis
showed that the compound crystallyzed from ethanol/water
with one hydration water molecule (Fig. 3. The corresponding CIF
file is included as a supplementary material).
Reactions of 1,2,5-thiadiazole 1,1-dioxides (1)
Reactions with o-PDA
The reactions of 1a,b with o-PDA yielded the corresponding
2,3-diaryl substituted quinoxalines 3 (experimental Section) and
sulfamide. A typical series of CV scans is shown in Fig. 4 for the
reaction of 1a with o-PDA at a molar ratio [o-PDA]/[1a] ¼ 3. The
.
.
initially observed 1a/1a ꢀ and 1a ꢀ/1a2ꢀ reversible couples (E1/2
ca ꢀ0.86 and ꢀ1.40 V, Fig. 4, solid line) were replaced at the end
of the reaction by a peak at ca ꢀ2.0 V (Fig. 4, dotted line), which
corresponds to the cathodic reduction of 3a, as it is identical to
that obtained in the CV of a solution of a synthesized sample of 3a
measured in the same experimental conditions (i.e., including the
addition of sulfamide). The CV of pure 3a is changed by the
1H NMR (d, TMS) in DMSO-d6: 8.09–7.69 (multiplet, CArom—H,
Table 1. Summary of studied reactions
6H), 3.79 (singlet, >CH2, 4H).
13
—
C NMR (d, TMS) same solution: 158.0 (C N), 141.1–119.0 (six
—
Substrate
Nucleophile
Products
signals, CAr), 45.0 (heterocyclic sp3 C-atoms).
IR (BrK, cm–1): 3450 and 3350 (H2O), 3030 (CArom—H), 2920 and
1a, b
1a, b, c
o-PDA
EDA
Quinoxalines
—
2850 (CAliph—H), 1630 (—C N), 1580 (CArom—H), 1440–1405
—
(CArom—H).
Dihydropyrazines (1a, b, c) or
pyrazines (1a, b), according to
the reaction condition used.
3,4-disubstituted thiadiazolidine
1,1-dioxide, dihydropyrazine or
pyrazine depending on the
reaction condition used.
2a
EDA
RESULTS AND DISCUSSION
A summary of the reactions studied in this work is given in
Table 1.
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´
M. V. MIRIFICO ET AL.
Figure 4. (-) CV of 1a 7.44 mM; (- - -): 7 h after the addition of o-PDA
(24 mM), (ꢁꢁꢁ) idem, after 24 h. Solvent: DMF, Supporting electrolyte: 0.1 M
NaClO4; sweep rate: 0.2 Vsꢀ1
Figure 5. (a) (-) CV of 1a (7.81 mM); (- - -) 10 min after addition of EDA
(7.80 mM); (-ꢁ-) idem after 92 min. (b) (–) CV of 4a (7.41 mM). Solvent: DMF,
Supporting electrolyte: 0.1 M NaClO4; sweep rate: 0.2 Vsꢀ1
presence of sulfamide. A CV of 3a with and without added
sulfamide is shown as a supplementary material in figure SM4c.
At intermediate times (Fig. 4, dashed line) the current intensity
decrease of the 1a signals was accompained by a proportional
increase of the 3a peak.
However, essays at larger [o-PDA]/[1a] molar ratios (ca 70)
showed that the decrease and almost total disappearance of the
peaks of 1a (at t ca 5 min) was followed by a time interval in which
only a practically featureless CV was observed. The CV peaks of 3a
appeared and developed only afterwards.
We have reported that completely saturated thiadiazolidine
cycles do not present voltammetric signals in the experimental
cathodic range.[9,10] Thus, it seems reasonable to relate this
almost featureless CV to a state of the reaction in which the
concentration of an intermediate thiadiazolidine, int1 (Scheme 2,
Ar: phenyl-) predominates. Accordingly, reaction 1 should be the
RDS at low o-PDA concentration. The increase in its rate, caused
by an [o-PDA] increase, would produce the accumulation of int1,
as reaction 2 becomes the RDS at high [o-PDA]/[1a] molar ratio.
Similar CV changes were found for the reactions of 1b with
o-PDA. These are provided as supplementary material (figures
SM1a and 1b).
Reactions with EDA
The reactions of 1a, b, and c with EDA yielded the corresponding
2,3-diaryl disubstituted dihydropyrazines 4 and sulfamide
(experimental Section). Under adequate reaction conditions, as
mentioned below, further reactions of the product with EDA
were observed.
The course of the reaction of 1a with EDA was followed by the
successive CV scans shown in Fig. 5a,b.
The CV cathodic peaks of 1a at ca ꢀ0.8 and ꢀ1.5 V (Fig. 5a, solid
line) decreased in current intensity, while two cathodic peaks at
ꢀ1.85 and ꢀ2.43 V increased after the addition of EDA
(Fig. 5a, broken line). The potential of these peaks suggested
their assignment to a thiadiazoline intermediate (int2, Scheme 3),
according to the known CV reduction characteristics of the
thiadiazolines of 1a.[6,9,10,26] The thiadiazoline peaks decreased
and disappeared subsequently, while
a
peak at ꢀ2.1 V
(Fig. 5a, dash-dot line) increased and remained thereafter. The
CV cathodic peak at ꢀ2.1 V corresponds to 4a (Scheme 3), as
shown by comparison with an authentic sample (Fig. 5b).
It was always observed, for all experimental molar [EDA]/[1a]
ratios (range: 1–15), that the CV current intensity of the peak(s) of
one compound decreased while those of its product(s)
simultaneously increased. No sign of accumulation of
a
non-electroactive compound, such as the thiadiazolidine
di-addition intermediate postulated as Int1 in Scheme 1, was
observed.
Although 4a was stable in well-degassed DMF solutions
(Fig. 6a, solid line), it was slowly oxidized to pyrazine, observed
through its CV cathodic peak at ca ꢀ2.5 V (Fig. 6a, dashed line),
particularly in the basic media provided by an excess of EDA. The
process is shown in Fig. 6a (dotted line). As a result, a mixture of
4a and its corresponding pyrazine was obtained in non-degassed
solutions with a high [EDA]/[1a] molar ratio. Fig. 6b illustrates this
situation for [EDA]/[1a] ¼ 15. Similar reactions were also
observed in other systems, but we have no explanation for
these slow oxidations in solution. We can only offer further
information: Given the following three solutions: (1) 4a in DMF
without degassing, (2) 4a þ EDA in degassed DMF, (3) 4a þ EDA
Scheme 2. Addition reaction of o-PDA to 1a,b to give the correspond-
ing quinoxalines 3a,b and sulfamide
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a-DIAMINES ADDITION TO THIADIAZOLE DERIVATIVES
Figure 7. CVs of DMF solutions of 1b and EDA at low and high [EDA]/[1b]
molar ratios. (a) 7.60 mM 1b, 37 mM EDA; (-) cathodic scan. (- - -) anodic
scan. (b) 7.60 mM 1b, 135 mM EDA; (-) cathodic scan, (- - -) anodic scan. All
scans were registered 1 day after solution preparation. Supporting
electrolyte: 0.3 M NaClO4, Sweep rate: 0.2 Vsꢀ1. Ei: rest potential, used
as the initial potential of all scans
Scheme 3. Addition reaction of EDA to 1 to give the corresponding
dihydropyrazines and pyrazines
in DMF without degassing; it was experimentally observed that
4a remained unaltered in (1), but transformed into pyrazine in
(2) and (3). If several ‘type 2’ solutions are prepared with different
EDA concentrations, the rate of the transformation of 4a into
pyrazine increased with the increase in EDA concentration. It is
also known that molecular oxygen is only slightly soluble in DMF
to begin with. Only a few microliters of EDA are added, so oxygen
could not have been incorporated as an EDA dissolution. It might
also be noted that the anions of 4b and 5a (shown below)
disappear rapidly when its solution is exposed to the air. However,
they can be kept indefinitely in DMF-EDA solutions prepared
essentially as solution (2) above, which therefore cannot contain
more than a negligible amount of oxygen.
disappearance of the 1b reversible CV couples (at ca ꢀ0.7 and
ꢀ1.3 V). However, upon exposure to the atmosphere, the peak at
ꢀ1.74 V disappeared and was replaced by the phenanthro
[9,10-b]-pyrazine CV peak at ꢀ2.04 V (irreversible, identical to that
of synthesized sample), which was the final product. The
dihydropyrazine intermediate 4b was identified through the
NMR spectrum of the solution before work-up (experimental
Section).
The reaction was also studied at larger [EDA]/[1b] molar ratios.
At a molar ratio [EDA]/[1b] ¼ 5, a CV scanned at the end of the
reaction (Fig. 7a; solid line) shows the pyrazine peak at ꢀ2.04 V.
An anodic peak at ꢀ0.55 V was also observed in the same solution
if the scan was started in the anodic direction from its equilibrium
potential Ei (Fig. 7a, broken line).
For even larger molar ratios (Fig. 7b, [EDA]/[1b] ꢂ 18), the
solution acquired a dark violet color and the CVs showed that the
anodic peak at ꢀ0.55 V has grown larger (Fig. 7b, broken line)
while the cathodic pyrazine peak at ꢀ2.04 V has decreased
(Fig. 7b, solid line). The color disappeared upon exposure of the
solution to the atmosphere.
The reaction of 1b with EDA was similar to its reaction with 1a.
The CV cathodic peak of 4b at ꢀ1.74 V was observed in the
reaction of 1b with EDA at a molar ratio [EDA]/[1b] ca 1, after the
We assigned the violet color and the anodic peak at ꢀ0.55 V to
the anion 4bꢀ (Scheme 4) on the basis of the following NMR data:
the 1H NMR spectrum of 0.15 mmol 4b, 1.2 mmol EDA in 0.761 g
DMF-d7, registered 2 h after solution preparation, presented
signals corresponding to phenanthro [9,10-b]-pyrazine, sulfa-
mide, and EDA in excess. In addition, a triplet at d (TMS) ¼ 4.41,
1H and a doublet at d ¼ 3.43, 2H were assigned to the
ꢀ
—
—CH —CH N— group in the 4b anion. The signals of
—
2
protonated EDA appeared as two multiplets partially super-
imposed on the solvent signal at ca d (TMS) ¼ 2.7–2.9. In the
13C NMR spectrum, the signals of 4bꢀ appeared at d (TMS) ¼ 64.4,
49.1, and 46.9. Both NMR spectra are included as supplementary
material (figures SM2a and 2b).
The reaction of 1c with EDA was somewhat analogous to those
.
of 1a or b, although surprisingly fast in comparison. The 1c/1c ꢀ
.
and 1c ꢀ/1c2ꢀ reversible couples (at ca ꢀ0.9 and ꢀ1.5 V), initially
Figure 6. (a) (–) CV of 7.41 mM 4a; (- - -) CV of 6.94 mM
2,3-diphenylpyrazine; (ꢁꢁꢁ) CV of 7.49 mM 4a and 40 mM EDA scanned
13 days after EDA addition. (b) (–) CV of 7.51 mM 1a and 115 mM EDA
scanned 1 day after EDA addition; (- - -) idem after a month. Solvent: DMF
Supporting electrolyte: 0.1 M NaClO4; sweep rate: 0.2 Vsꢀ1
observed for a 6.73 mM 1c solution in DMF solvent, disappeared
almost instantaneously when EDA was added to the solution
even in a [EDA]/[1c] molar ratio slightly larger than 1. An almost
flat CV was observed for a very short time (ca 90 s). An irreversible
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´
M. V. MIRIFICO ET AL.
Scheme 4. 4bꢀ formation reaction
cathodic peak at ꢀ1.92 V, and a couple at ca ꢀ2.50 V appeared
and remained thereafter. The final CV was identical to that
obtained for a solution of 4c and sulfamide.
As it was the case for 1b, a solution of 1c in a large excess of
EDA ([EDA]/[1c] ca 18) developed a dark violet color that rapidly
disappeared in the presence of air. We believe that an anion of 4c
was responsible for the color, but it could not be detected by
NMR spectroscopy because the very large excess of EDA blocked
other signals.
appreciably decreased current intensity 2 days after solution
preparation (Fig. 8a, dashed line), and had practically disappeared
7 days later (Fig. 8a, dotted line), without being replaced by any
other CV signal. As it was mentioned above, this behavior
suggested the formation of an electroinactive thiadiazolidine 5a
(Fig. 9).
In the 13C NMR spectrum of a similar solution (figure SM3a,
supplementary material) the signal of the single heterocyclic sp3
C-atom of 2a (at d (TMS) ¼ 75.6) (figure SM3b, supplementary
material) was replaced by two signals of similar intensity (at d
(TMS) ¼ 87.8 and 77.3) corresponding to the two different sp3
C-atoms of 5a. The single 1H NMR resonance of EDA (d
(TMS) ¼ 2.59) decreased and two triplets centered at d (TMS) ca
3.2 and 2.7, assigned to the methylene protons in the EDA
substituent of 5a appeared (figure SM3c, supplementary
material), and the 2a 1H signal at d ¼ 6.05 (H bonded to
heterocyclic sp3 C-atom) (figure SM3d, supplementary material)
was displaced to higher field (d ¼ 5.0), as its adjacent sp2 C-atom,
double-bonded to N, was changed into the EDA-substituted sp3
C-atom of 5a.
Reaction of 2a with EDA
—
Given that thiadiazolines have only one C N double bond, a
—
nucleophilic addition to give thiadiazolidines was their expected
reaction with a strong nucleophile, such as EDA. This was in fact
initially observed in the reaction of 2a with EDA in DMF solution,
as indicated by CV and NMR spectra. The thiadiazolidine
underwent further reaction as mentioned below.
CV showed that the initial cathodic signal of 2a at ꢀ2.11 V
decreased with time without being replaced by any other CV
peak. As it is shown in Fig. 8, for a DMF solution with [EDA]/
[2a] ¼ 4.4, the initial 2a peak (Fig. 8a, solid line) showed an
However, it was observed that after the disappearance of
the 2a CV peak, an anodic signal appeared and grew.
Fig. 8a (dash-dot line) shows this signal at its full strength,
43 days after solution preparation. The NMR spectra (see figures
SM4a and SM4b, supplementary material) also changed: new
signals (at d (TMS) ¼ 138.5 and 43.5) developed in the 13C NMR
1
and in the H NMR (at d (TMS) ¼ 3.6) spectrum. The anodic CV
signal suggested the formation of an anion derived from 5a. A
simulation of the 13C-NMR of possible anions of 5a agreed with
that assumption, but could not decide among them.
In carefully degassed solutions, kept in well-stoppered vessels,
the spectra remained unchanged thereafter. But if the vessel was
opened and exposed to the atmosphere, the anion reacted to
yield 4a as could be observed in CV scans by the disappearance
of the anodic peak of the anion (Fig. 8b, solid line), and its
replacement by the cathodic peaks of 4a and that of the pyrazine
(Fig. 8b, dashed line). On continuing the exposure, only the
pyrazine peak remained (not shown).
Figure 8. CVs of a solution of 2a (7.34 mM) and EDA (32 mM); ([EDA]/
[2a] ¼ 4.4). The scans were run immediately after dilution with DMF of a
concentrated reaction solution ([2a] ¼ 0.15 M; [EDA] ¼ 0.66 M) in DMF, at
the following times after reactants mixture: 8(a) (-) t ¼ 0, (- - -) t ¼ 2 days;
(ꢁꢁꢁ) t ¼ 7 days; (-ꢁ-) t ¼ 43 days, anodic scan. 8b: (-) 2.5 h after exposure to
the atmosphere, anodic scan; (- - -): 2.5 h after exposure to the atmos-
phere, cathodic scan. Sweep rate: 0.2 Vsꢀ1, supporting electrolyte: 0.45 M
NaClO4
Figure 9. Product of the EDA addition to 2a
J. Phys. Org. Chem. 2009, 22 163–169
Copyright ß 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/poc

a-DIAMINES ADDITION TO THIADIAZOLE DERIVATIVES
[5] E. L. Svartman, M. F. Rozas, O. E. Piro, E. E. Castellano, M. V. Mir´ıfico,
Synthesis 2006, 2313–2318.
CONCLUSIONS
[6] S. L. Aimone, J. A. Caram, M. V. Mir´ıfico, E. J. Vasini, J. Phys. Org. Chem.
2000, 13, 272–282.
[7] S. V. Pansare, A. N. Rai, S. N. Kate, Synlett 1998, 623–624.
[8] E. E. Castellano, O. E. Piro, J. A. Caram, M. V. Mir´ıfico, S. L. Aimone, E. J.
While the addition of unsubstituted or adequately substituted
ureas and thioureas to 3,4-diphenyl-1,2,5-thiadiazole 1,1-dioxide
was found to give stable five-five fusion bicyclic compounds
(Fig. 1), the addition of a-diamines did not produce the expected
five-six fusion bicyclic products. Instead, sulfamide loss was
observed and dihydropyrazines or quinoxalines were formed in
the reactions with EDA or o-PDA. The experimental results only
allowed the conjecture of an unstable intermediate with the
five-six fusion bicyclic structure for the reactions of 1a and 1b
with o-PDA (int1 in Scheme 2). The new compound: acenaphtho
[5,6-b]-2,3-dihydropyrazine was synthesized and characterized.
´
Vasini, A. Marquez-Lucero, D. Glossman-Mitnik, J. Mol. Struct. 2002,
604, 195–203.
[9] J. A. Caram, M. V. Mir´ıfico, S. L. Aimone, O. E. Piro, E. E. Castellano, E. J.
Vasini, J. Phys. Org. Chem. 2004, 17, 1091–1098.
[10] J. A. Caram, O. E. Piro, E. E. Castellano, M. V. Mir´ıfico, E. J. Vasini, J. Phys.
Org. Chem. 2006, 19, 229–237.
[11] J. Heinze, Angewandte Chemie Int. Ed. 1984, 23, 831–847.
[12] M. V. Mir´ıfico, E. J. Vasini, J. A. J. Caram, Phys. Org. Chem. 2007, 20, 1–7.
[13] J. B. Wright, J. Org. Chem. 1964, 29, 1905–1909.
[14] J. A. Riddick, W. B. Bunger, In Techniques of Chemistry, Vol. 2. (Ed.: A.
Weissberger) Wiley-Interscience, New York, 1970. 201.
[15] D. D. Perrin, W. L. F. Armarego, Purification of Laboratory Chemicals,
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[16] J. F. Coetzee, Recommended Methods for Purification of Solvents and
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[17] A. I. Vogel, A Text-book of Practical Organic Chemistry, Longmans
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[18] SDBSWeb: http://riodb01.ibase.aist.go.jp/sdbs/ (National Institute of
Advanced Industrial Science and Technology, date of access: 03/25/
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Acknowledgements
This work was financially supported by the Consejo Nacional de
´
´
Investigaciones Cient´ıficas y Tecnicas (CONICET), the Comision de
Investigaciones Cient´ıficas de la Provincia de Buenos Aires (CIC
Pcia. Bs.As.), and the Universidad Nacional de La Plata (UNLP),
Facultad de Ciencias Exactas, Departamento de Qu´ımica and
Facultad de Ingenier´ıa, Departamento de Ingenier´ıa Qu´ımica.
M. V. M, J. A. C., and O. E. P. are researchers of CONICET and
UNLP, E. J. V. is researcher of CIC Pcia. Bs.As and UNLP.
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J. Phys. Org. Chem. 2009, 22 163–169