Synthesis of 6,7-Dihydropyrrolo[2,1-c][1,3]thiazino[3,2-a]pyrazine-4(11bH)-(thi)ones from 1,2-Dithiolo-3-(thi)ones

Article abstract of DOI:10.1002/ejoc.201900142

An efficient synthesis of 6,7-dihydropyrrolo[2,1-c][1,3]thi-azino[3,2-a]pyrazine-4(11bH)-(thi)ones from readily available 1,2-di-thiolo-3-(thi)ones and 3,4-dihydropyrrolo[1,2-a]pyrazine is reported. The S2 atom in both monocyclic and fused 1,2-dithioles is selectively replaced by aminomethylene to afford fused, rigid six-membered 1,3-thiazines. The scope of this two-step one-pot reaction was investigated: 1,2-dithiolo-3-ones were more reactive than the corresponding 1,2-dithiole-3-thiones. Optimized reaction conditions and a mechanistic rationale for the ring transformation are presented.

Full text of DOI:10.1002/ejoc.201900142

A Journal of
Accepted Article
Title: Synthesis of 6,7-dihydropyrrolo[2,1-c][1,3]thiazino[3,2-
a]pyrazine-4(11bH)-(thi)ones from 1,2-dithiolo-3-(thi)ones
Authors: Vladimir A Ogurtsov, Yury V Karpychev, Yulia Nelyubina, Petr
V Primakov, Panayiotis A Koutentis, and Oleg A Rakitin
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900142
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10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
Synthesis of 6,7-dihydropyrrolo[2,1-c][1,3]thiazino[3,2-a]pyrazine-
4(11bH)-(thi)ones from 1,2-dithiolo-3-(thi)ones
Vladimir A. Ogurtsov,[a] Yury V. Karpychev,[b] Yulia V. Nelyubina,[c] Petr V. Primakov,[c],[d] Panayiotis A.
Koutentis,[e] and Oleg A. Rakitin*[a],[f]
Abstract: An efficient synthesis of 6,7-dihydropyrrolo[2,1-c][1,3]thi-
azino[3,2-a]pyrazine-4(11bH)-(thi)ones from readily available 1,2-di-
thiolo-3-(thi)ones and 3,4-dihydropyrrolo[1,2-а]pyrazine is reported.
The S2 atom in both monocyclic and fused 1,2-dithioles is selectively
replaced by aminomethylene to afford fused, rigid six-membered
1,3-thiazines. The scope of this two-step one-pot reaction was
investigated: 1,2-dithiolo-3-ones were more reactive than the
corresponding 1,2-dithiole-3-thiones. Optimized reaction conditions
and
a mechanistic rationale for the ring transformation are
presented.
Introduction
In 2008, we reported a new reaction of fused 1,2-dithiole-3-
thiones (e.g., compd 1a) with 3,4-dihydropyrrolo[1,2-a]pyrazine
(2) that gave pyrazino[2,1-b][1,3]thiazines 3.1
A
similar
Scheme 1. Synthesis of pyrazino[2,1-b][1,3]thiazines 3a and
3l from 1,2-dithiole-3-thiones 1 and through thiete-2-thione 4.
Pyrazino[2,1-b][1,3]thiazine core shown in red color.
transform-ation was also be achieved in two distinct steps by
first treating the monocyclic 1,2-dithiole-3-thione 1b with a sulfur
extrusion agent such as a trimethylphosphite (1 equiv), to give a
rare four-membered thiete-2-thione 4 in 92% yield. Subsequent
treatment of the thiete 4 with dihydropyrrolopyrazine 2 (1 equiv)
gave the fused 1,3-thiazine-4-thione 3l 95% yield (Scheme 1).2
Nitrogen-bridged heterocycles find many uses in a wide
range of applications and are important classes of compounds.3
Interestingly, relatively few pyrazino[2,1-b][1,3]thiazines have
been reported. Nevertheless, this nitrogen-bridged bicyclic
system is present as a substructure in various natural products,
epicoccin A,4 D,5 E,6 F,6 I5 and the structurally similar
eutypellazines A, B, F, G, and H7 that are all
thiodiketopiperazine-type alkaloids (Figure 1).
[a]
Dr. V. A. Ogurtsov, Prof. Dr. O. A. Rakitin, N. D. Zelinsky Institute of
Organic Chemistry, Russian Academy of Sciences, 47 Leninsky
Prospekt, 119991 Moscow, Russia.
E-mail: orakitin@ioc.ac.ru
http://zioc.ru/institute/laboratories/laboratory-of-polysulphur-nitrogen-
heterocycles-n31
[b]
[c]
Dr. Yu. V. Karpychev, JSC State Scientific Research Institute
“Kristall”, 606007 Dzerzhinsk, Nizhny Novgorod Region, Russian
Federation.
Prof. Dr. Yu. V. Nelyubina, Mr. P. V. Primakov, A. N. Nesmeyanov
Institute of Organoelement Compounds, Russian Academy of
Sciences, 119991 Moscow, Russia
Figure 1. Thiodiketopiperazine-type alkaloids epicoccin A and eutypellazine
A. Pyrazino[2,1-b][1,3]thiazine core shown in red color.
[d]
[e]
Mr. P. V. Primakov, Department of Chemistry, Moscow State
University, 119899 Moscow, Russia
Prof. Dr. P. A. Koutentis, Department of Chemistry, University of
Cyprus, P. O. Box 20537, 1678 Nicosia, Cyprus
E-mail: koutenti@ucy.ac.cy
http://ucy.ac.cy/dir/en/component/comprofiler/userprofile/koutenti
Prof. Dr. O. A. Rakitin, Nanotechnology Education and Research
Center, South Ural State University, 454080 Chelyabinsk, Russian
Federation
Supporting information for this article is given via a link at the end of
the document.
Several thiodiketopiperazine-type alkaloids show biological
properties such as antimicrobial,4 anti-inflammatory,5 and anti-
HIV7 activities. Other non-natural compounds containing the
pyrazino[2,1-b][1,3]thiazine substructure also show biological
activities. The tetracyclic azasugar-fused benzo[e][1,3]thiazin-
4-ones (e.g., compound 5) show HIV reverse transcriptase
(RT) inhibitory activities,8 while compound 6 shows HIV
[f]
integrase
inhibition.9
Furthermore,
scaffold-based
tripeptidomimetic CXCR4 antagonists that contain the
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10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
pyrazino[2,1-b][1,3]thiazine substructure have been prepared10
(e.g., compound 7, Figure 2).11
both reagents 1a and 2 in various solvents and heating them
under reflux: no reaction was observed in benzene, MeCN or
pyridine heated to reflux, or in DMSO, sulfolane or DMF heated
to ca. 95 °С over 8 h. Pure thione 1a was also not decomposed
in boiling benzene, THF, 1,4-dioxane, and MeCN, or in hot (ca.
95 oC) pyridine, DMSO, sulfolane and DMF. The addition to
solutions of thione 1a in benzene or MeCN of sulfur-extrusion
reagents,
triphenylphosphine,
trimethylphosphite,
triphenylantimony or sodium phenylsulfinate, also led to no
reaction.
If a neat mixture of reagents 1a and 2 (8 equiv) was treated
with Et3N (8 equiv) and heated at reflux for two days, the
pyrazino[2,1-b][1,3]thiazine 3a formed in a moderate 40% yield.
Despite this, we were unable to identify a suitable additive and
reaction conditions to improve on this yield.
At this point, we examined the reaction of other fused (1a-g)
and monocyclic (1h-m) 1,2-dithiole-3-thiones with excess neat
dihydropyrrolopyrazine 2 to give 1,3-thiazine-4-thiones 3 and
found that the product yields were very dependent on the
structure of 1,2-dithiole-3-thiones (Table 1). 1,2-Dithiole-3-
thiones 1a-c were treated up to disappearance of the starting
dithiole-thione, and others up to maximum yield of the product 3
by TLC data. The most reactive of the 1,2-dithiole-3-thiones
screened were those fused with electron-withdrawing cycles. For
example, pyrido-fused 1b and dihydroindenone 1d reacted
relatively rapidly with pyrrolopyrazine 2 in 1 d and 1 h,
respectively (Table 1, entries 2 and 4) (cf. benzo-fused 1a, 3 d).
Other 1,2-dithiole-3-thiones, such as fused 1e-g and monocyclic
1h, 1i, where the dithiole-thione was not fused with electron-
withdrawing cycles, required prolonged stirring, and failed to
completely consume the dithiolethiones 1d-1f even after 60 days
(Table 1). If a neat mixture of the reagents 1c or 1f and 2 (7
equiv) was heated at 40 °С significant decomposition was
observed after 4-6 h; the reaction did not finish after 24 h and
compounds 3c and 3f were isolated with the yields 22% and
11%, correspondingly. Lower yields of 3c and 3f were obtained
by heating of the reaction mixtures at 60 °С and at 80 °С.
Figure 2. Non-natural pyrazino[2,1-b][1,3]thiazines.
Routes to the pyrazino[2,1-b][1,3]thiazine ring system remain
somewhat limited and involve either the construction of the
pyrazine directly onto a 1,3-thiazine,8a or construction of the 1,3-
thiazine onto a pyrazine moiety.12 Both rings can also be
constructed in one pot,13 which can be also be achieved via
solid-phase mediated multi component reactions.14
In light of the current interest in compounds that contain the
pyrazino[2,1-b][1,3]thiazine substructure we considered that our
prior synthesis that prepares the ring system quickly and in high
yield from 3H-1,2-dithioles and 3,4-dihydropyrrolo[1,2-a]pyrazine
2, both readily available starting materials, to be worthy of
further study. As such, herein, we investigate the scope of this
reaction, leading to several new 6,7-dihydropyrrolo[2,1-
c][1,3]thiazino[3,2-a]pyrazine-4(11bH)-(thi)ones, including
crystallographic study of a key analogue.
a
Table 1. Reaction of 1,2-dithiole-3-thiones 1a-m with 3,4-dihydropyrrolo[1,2-
а]pyrazine 2.
Yields (%)
Time
Entry
1
R1
R2
(d)
Results and Discussion
1
3
Reaction of 1,2-dithiole-3-thiones 1 with 3,4-
dihydropyrrolo[1,2-а]pyrazine 2
1a
2a
1a
1b
3
0
3a (64)1
As mentioned above, 3H-benzo[c][1,2]dithiole-3-thione (1a)
reacts with excess 3,4-dihydropyrrolo[1,2-а]pyrazine (2) (10
equiv) at ca. 20 °C for 72 h, to give the pyrazino[2,1-
b][1,3]thiazine 3a in 64% yield (Scheme 1).1 While this
transformation requires a large excess of pyrazine 2, it should
be noted that unreacted dihydropyrrolopyrazine 2 can be fully
recovered from the reaction mixture. Nevertheless, attempts
were made to improve the reaction conditions and increase the
product yield. These included mixing equimolar quantities of
1
0
0
3b (88)
3c (81)
3a
1c
60
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10.1002/ejoc.201900142
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1o, the reactions with pyrrolopyrazine 2 and trimethylphosphite
led to decomposition even at room temperature. In contrast, 1,2-
dithi-ole-4-thiones containing electron releasing groups, such as
5-methyl-3H-1,2-dithiole-3-thione 1p or 4,5,6,7-tetrahydro-3H-
4a
1d
1e
0.04
60
0
3d (49)1
3e (40)
benzo-[c][1,2]dithiole-3-thione
1r,
did not
react
with
pyrrolopyrazine 2 (1 equiv) in hot MeCN with or without sulfur-
extrusion reagents.
5a
58
6a
1f
60
62
3f (37)
Figure 3. Structures of 1,2-dithioles 1n-r.
Since
1,2-dithiole-3-thiones
to
1a-m
give
reacted
the pyrazino[2,1-
with
7a
1g
60
13
3g (31)
dihydropyrrolo-pyrazine
2
b][1,3]thiazine-4-thiones 3a-m (Table 1), we considered whether
the reaction could be extended to 3H-1,2-dithiol-3-ones 8. A
preliminary screen of reagents and conditions for the reaction of
the benzo-fused 3H-1,2-dithiol-3-one 8a and pyrrolopyrazine 2
(1 equiv) identified that the reaction worked best when
triphenylphosphine (1 equiv) was used as thiophile to activate
the dithiole in dry benzene at ca. 20 °C, for 3 h, which gave the
expected benzo-fused 1,3-thiazin-4-one 9a in 87% yield together
with triphenylphosphine sulfide as by-product in near
quantitative yield. These reaction conditions also worked for
both pyrido-fused 3H-1,2-dithiol-3-one 8b and the monocyclic 5-
phenyl-3H-1,2-dithiol-3-one 8c, to give in high yields the
expected 1,3-thiazin-4-ones 9b (90%) and 9c (98%),
respectively (Scheme 2).
8a
1h
1i
H
Ph
Cl
Cl
Cl
Cl
Ph
H
60
21
10
3h (69)1
3i (70)
3j (38)
3k (45)
3l (35)
3m (29)
9a
60
10b
11b
12b
13b
1j
SPy
0.08
0.08
0.08
0.08
1l
SPh
1k
1m
OPh
morpholinyl
a 2 (10 equiv), ca. 20 °C; b 2 (1 equiv), P(OMe)3 (1 equiv), MeCN, ca. 82 °C.
Monocyclic 4- or 5-phenyl-substituted 1,2-dithiole-3-thiones
1h and 1i, respectively, also reacted with excess 2 relatively
slowly (60 days) to give the expected thiazines 3h (69%) and 3i
(70%) in relatively good yields (Table 1, entries 8 & 9). However,
when the monocyclic 1,2-dithiole-3-thiones contained a 4-chloro
substituent, i.e. 4-chloro-5-(substituted)-3H-1,2-dithiole-3-thione
1j-m, the reactions with excess pyrrolopyrazine 2 at ca. 20 °C
for 24 h led only to decomposition of the 1,2-dithioles.
Introducing a solvent in these reactions failed to improve the
outcome. An equimolar mixture of dithiole 1j and pyrrolopyrazine
2 in either MeCN, benzene, pyridine, PhCl or xylene at ca. 20 °C
or when heated to reflux for several hours failed to react. As
such, we then introduced sulfur-extrusion reagents. In the case
of 1,2-dithiole-3-thione 1j the reaction with pyrrolopyrazine 2 (1
Scheme 2. Synthesis of 1,3-thiazin-4-ones 9 from 1,2-dithiol-3-ones 8.
Somewhat more interesting was our effort to extend these
conditions to unsymmetrical bis([1,2]dithiolo)[3,4-b:4',3'-e][1,4]-
thiazin-3-one 10, readily available from our prior work,16 that
contained both thiocarbonyl and carbonyl dithiole moieties.
Treating the unsymmetrical bisdithiole 10 with pyrrolopyrazine 2
(1 equiv), triphenylphosphine (1 equiv) in dry benzene at ca.
equiv)
in
the
presence
of
triphenylphosphine
or
trimethylphosphite (1 equiv) in acetonitrile gave thiazinethione 3j
in low 31 and 38% yields, respectively. Since trimethylphosphite
gave the desired product in higher yield (Table 1, entry 10), we
applied it to the remaining 4-chloro-1,2-dithioles (1k-m) which
gave the respective thiazines 3k-m in low to moderate yields
(29-45%) (Table 1, entries 11-13).
20
°C
for
3
h
gave
4-ethyl-5-thioxo-3H,4H,5H-
(11) in
bis([1,2]dithiolo)[3,4-b:4',3'-e][1,4]thiazin-3-one
a
moderate 45% yield (Scheme 3). Structural evidence for
compound 11 was inconclusive based solely on spectroscopic
data, however, the bisdithiole 10 is known to react with DMAD in
Worthy of note, if the 1,2-dithiole-3-thione 1 contained a
good nucleofuge at C-5 e.g., a chloro 1n or phenylsulfonyl group
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10.1002/ejoc.201900142
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the presence of Lewis acid (scandium triflate) to give 1,3-dithiole
12.17 As such, compound 11 was reacted with DMAD (1 equiv)
in the presence of ytterbium triflate (0.2 equiv), to give the 1,3-
dithiole 13 in 73% yield (Scheme 3). The same product was also
independently prepared in 66% yield by treating 1,2-dithiole 12
with pyrrolopyrazine 2 and triphenylphosphine (Scheme 3). This
supported the structural assignment of compound 11 and
tentatively supported that the dithiolone moiety was more
reactive to the pyrrolopyrazine 2 than the dithiole-3-thione
moiety.
Figure 4. General view of pyrrolopyrazinothiazinone 14 (R isomer shown) in
representation of atoms via thermal ellipsoids at 50% probability level.
Compound 14 crystallizes as a 50:50 racemic mixture of the
R and S isomers, the chirality being attributed to the chiral
centre at the C7 (crystallographic numbering). In both isomers,
the five-membered rings are essentially planar within ±0.02 Å,
while the six-membered rings adopt half-chair conformations
with the atoms C7 and C12 (crystallographic numbering)
deviating the most from the mean-plane of the thiazinone and
pyrazine moieties by ~0.9 and 0.7 Å, respectively. The
molecules form infinite chains of chirally equivalent molecules
that are connected via nearly equidistant intermolecular
Scheme 3. Synthesis of 1,3-thiazin-4-one 11.
…
intrachain S O interactions between the carbonyl oxygen and
the two sulfurs of the dithiole’s S-S bond [d(O…S-C) 2.9883(16) Å,
…
…
…
O
S-C 169.32(8)° and d(O…S-C) 3.1865(16) Å,
O
S-C
Interestingly, this new heteroatom rich fused pentacycle 11
was unstable in either DCM or dry benzene solution, losing one
equivalent of elemental sulfur to give a new pyrrole system 14 in
near quantitative yield (Scheme 4).
155.79(8)° for R isomer and d(O…S-C) 2.9335(16) Å, O S-C
169.65(8)° and d(O…S-C) 3.2181(16) Å, O S-C 153.21(8)° for S
…
isomer (see Figure S45, Supporting Information)], presumably
these interactions involve the carbonyl oxygen lone pair and the
σ* orbitals of the dithiole C-S bonds. Similar near equidistant
intermolecular interactions with disulfide containing heteroles
have been observed.19 These chains align in slipped stacks
where each alternating chain is composed of molecules with the
…
same chirality. Weak interchain C-H S= interactions [d(C-H…S)
…
3.6802(24) Å, C-H S 160.2(1)°] exist between the pyrrole rings
and the dithiole thiocarbonyl, between chirally non-equivalent
molecules, which assist in the packing. Furthermore, these
chains align in slipped stacks where each alternating chain is
composed of molecules with opposite chirality. Multiple weak
…
…
…
…
…
C=O S, S S, C-H O, C-H N and C-H π interactions
assist in the solid state packing, furthermore, the voids of the
resulting 3 D framework are occupied by the two water and one
n-hexane molecule, which presumably arise from the
reсrystallisation solvents.
Scheme 4. Synthesis of pentacycle 14.
Despite the instability of the pentacycle 11 it could readily be
further reacted with neat pyrrolopyrazine 2 (7 equiv) at ca. 20 °C
for 4 days to give the in good yield the new heptacyclic system
16 (74%) (Scheme 5). Not surprisingly, considering the long
reaction conditions (4 days) the 1,4-thiazine suffered a ring
contraction to give the pyrrole system. This highly unusual
sulfur-nitrogen fused heterocycle has two sulfur and five ring
nitrogens, four of which are bridge head nitrogens and also two
chiral centers that should lead to diastereomers. Efforts are now
underway to grow single crystals of this system to enable a
detailed crystallographic study. The high heteroatom
The structure of the pentacyclic pyrrole 14 was supported by
single crystal X-ray diffraction studies (Figure 4) and by a semi-
independent synthesis by reacting the bis-dithiolopyrrole 15 with
pyrrolopyrazine 2 in the presence of triphenylphosphine which
gave product 14 in 75% yield, which was spectroscopically
identical to that formed from the above ring contraction (Scheme
4). Such ring contractions of 1,4-thiazines are rare with only few
known examples to date.18
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10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
composition, non-planar, concave but rigid geometry is
promising for future applications. In a related effort to study the
ability to carry out a one pot cyclisation and 1,4-thiazine ring
contraction we were able to similarly react the unsymmetrical
bisdithiole 10 with pyrrolopyrazine 2 (1 equiv) in dry benzene
heated to reflux for 3 h to get the pyrrole 14 in 56% yield
(Scheme 5).
Scheme 7. The plausible reaction mechanisms (Routes A and B) for the
formation of 1,3-thiazines (X = S or O).
Conclusions
Scheme 5. Synthesis of 1,3-thiazin-4-ones 14 and 16.
Monocyclic and fused 3H-1,2-dithiole-3-(thi)ones treated either
with neat excess 3,4-dihydropyrrolo[1,2-a]pyrazine (2) or in a 1:1
stoichiometry when a thiophilic additive such as triphenyl-
phosphine or trimethylphosphite is used, give under relatively
We also considered extending the 1,2-dithiole to 1,3-thiazine
conversion to a non-cyclic imine, N-methyl-1-phenylmethanimine
17. In our hands, the most reactive bis[1,2]dithiolo[1,4]pyrrole 15,
that contained both thione and keto groups, failed to react with
imine 17 (1 equiv) in hot benzene, which was in stark contrast to
the cyclic pyrrolopyrazine 2. Nevertheless, repeating the
reaction in the presence of Ph3P (1 equiv) gave after 3 h the 1,3-
thiazine-4-one 18 in 54% yield, together with a near quantitative
amount of Ph3PS (Scheme 6).
mild
conditions
6,7-dihydropyrrolo[2,1-c][1,3]thiazino[3,2-
a]pyrazines-4(11bH)-(thi)ones in moderate to excellent yields.
The cyclisation is chemoselective preferring 3H-1,2-dithiol-3-
ones vs 3H-1,2-dithiol-3-thiones and provides access to a
partially saturated racemic mixtures of rigid non planar polycyclic
heterocycles rich in both sulfur and nitrogen starting from readily
available planar heterocycles. In several cases in situ sulfur
extrusion from the formed 1,4-thiazines was observed to give
new pyrrolo-fused systems. The biological properties of the new
pyrrolo[2,1-c][1,3]-thiazino[3,2-a]pyrazines
and
efforts
to
broaden the scope of this cyclisation reaction to non-cyclic
imines are in progress and will be reported at a later date.
Scheme 6. Synthesis of 1,3-thiazin-4-one 18.
Experimental Section
Plausible reaction mechanisms for the conversion of 1,2-
dithioles to 1,3-thiazines in the presence of imines are shown in
the Scheme 7. In the absence of phosphine or phosphite, we
presume the first step is the attack of imine nitrogen at the C3
position of the 1,2-dithiole 19 to give the ring opened
intermediate 20 that loses sulfur via a sulfur chain extension
mechanism to give the sulfide 21 which rapidly cyclizes onto the
iminium to afford the thiazine 22 (Route A). With weakly
nucleophilic imines, the use of a sulfur-extrusion reagent (Ph3P
or MeO3P) helps activate the 1,2-dithiole 19 by converting it to a
more reactive thiete 24, which tentatively then reacts rapidly with
the imine to give directly the monosulfide intermediate 21 (Route
B) (cf. thiete 4, Scheme 1).
General Information. The reagents were purchased from commercial
sources and used as received. 3H-Benzo[c][1,2]dithiole-3-thione (1a)20,
3H-[1,2]dithiolo[3,4-b]pyridine-3-thione (1b),21 4-ethyl-[1,2]dithiolo[4,3-
b]indole-3(4H)-thione (1c),22 3-thioxoindeno[1,2-c][1,2]dithiol-4(3H)-one
(1d),23 5-phenyl-3H-1,2-dithiole-3-thione (1h),21 4-phenyl-3H-1,2-dithiole-
3-thione (1i),24 4-chloro-5-(pyrid-2-ylthio)-3H-1,2-dithiole-3-thione (1j),25
4-chloro-5-(phenylthio)-3H-1,2-dithiole-3-thione
(1k),25
4-chloro-5-
phenoxy-3H-1,2-dithiole-3-thione (1l),25 4-chloro-5-morpholino-3H-1,2-
dithiole-3-thione (1m),25 3,4-dihydropyrrolo[1,2-a]pyrazine (2),26 3H-
benzo[c][1,2]-dithiol-3-one (8a),27 3H-[1,2]dithiolo[3,4-b]pyridine-3-one
(8b),28 5-phenyl-3H-1,2-dithiole-3-one (8c),28 4-ethyl-5-thioxo-3H,4H,5H-
bis([1,2]dithiolo)-[3,4-b:4',3'-e][1,4]thiazin-3-one (10),16 dimethyl 2-(4-
ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-ylidene)-
1,3-dithiole-4,5-di-carboxylate (12),17 4-ethyl-5-thioxo-4,5-dihydro-3H-
bis([1,2]dithiolo)[4,3-b:3',4'-d]pyrrol-3-one
(15),18a
N-methyl-1-
phenylmethanimine (17)29 were prepared according to the published
methods and characterized by NMR spectra. All synthetic operations
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
2
were performed under a dry argon atmosphere. Solvents were purified by
distillation from the appropriate drying agents.
6.75-6.80 (m, 1H, ArH), 7.21 (dd, 1H, ArH, 1J = 8.1, J = 4.4), 8.50 (dd,
1H, ArH, 1J = 4.4, 2J = 1.5), 8.72 (dd, 1H, ArH, 1J = 8.1, 2J = 1.5). 13C
NMR (75 MHz, CDCl3, δ, ppm): 44.4 and 48.9 (both for 1CH, CH2CH2),
59.3 (CH), 108.0, 109.5, 121.1, 121.2, 142.3 and 151.8 (6C, ArH), 120.4,
131.1 and 156.1 (3 sp2 C), 192.6 (C=S). MS (EI, 70 eV), m/z (I, %): 273
[M]+ (16), 153 (20), 119 (29), 106 (100), 93 (33).
Elemental analyses for C, H and N were performed with Perkin Elmer
2400 Elemental Analyser. Melting points were determined on a Kofler
1
hot-stage apparatus and are uncorrected. H and 13C NMR spectra were
taken with a Bruker AM-300 machine (at frequencies of 300.1 and 75.5
MHz), Bruker AC-200 machine (at frequency of 50.32 MHz) and Bruker
AV-400 machine (at frequency of 400.16 MHz) in CDCl3 or DMSO-d6
solutions, with TMS as the standard. J values are given in Hz. MS
spectra (EI, 70 eV) were obtained with a Finnigan MAT INCOS 50
instrument. IR spectra were measured with a Bruker “Alpha-T” instrument
in KBr pellets.
9-Ethyl-5,6,9,13b-tetrahydro-14aH-
pyrrolo[2'',1'':3',4']pyrazino[2',1':2,3][1,3]thiazino[5,6-b]indole-8(8aH)-
thione (3c). Yellow solid, (275 mg, 81%), Rf = 0.67 (CH2Cl2/hexane,
65:35). Mp = 162–163 °С. Found: C, 63.64; H, 5.00; N, 12.29. Anal.
calcd for C18H17N3S2 (%):C, 63.68; H, 5.05; N, 12.38. IR νmax (KBr, cm–1):
2920 and 2964 (CH), 1468, 1460, 1364, 1336, 1328, 1292, 1284, 1232,
1160, 1072, 928, 752, 728. 1H NMR (300 MHz, CDCl3, δ, ppm, J/Hz):
1.45 (t, 3H, CH3, J = 7.1), 4.16 (ddd, 1H, CH2, 1J = 13.4, 2J = 8.7, 3J =
4.4), 4.25-4.38 (m, 2H, CH2), 4.73 and 5.09 (two dqw for 2H, CH2CH3, 1J
X-Ray Diffraction: Crystals of 14 (C64.38H64.38N12O5.08S16, M = 1600.46)
are monoclinic, space group P21/n, at 120 K: a = 7.6376(3), b =
17.4612(7), c = 26.4967(11) Å, β = 94.9680(10)°, V = 3520.4(2) Å3, Z = 2,
dcalc = 1.510 gcm–3, (MoK) = 5.51 сm-1, F(000) = 1663. Intensities of
= 14.2, 2J = 7.1), 5.29 (ddd, 1H, CH2, J = 13.7, 2J = 3.7, 3J = 3.7), 6.22-
1
6.26 (m, 2H, ArH), 6.31 (dd, 1H, ArH, 1J = 3.6, 2J = 1.3), 6.77 (dd, 1H,
1
2
1
2
3
ArH, J = 2.6, J = 1.6), 7.16 (ddd, 1H, ArH, J = 8.1, J = 5.9, J = 2.2),
28282 reflections were measured with
a Bruker APEX2 CCD
7.36-7.46 (m, 2H, ArH), 7.58 (dd, 1H, ArH, J = 8.1, J = 0.9). 13C NMR
(75 MHz, CDCl3, δ, ppm): 15.4 (CH3), 40.2, 44.9 and 46.3 (all three for
1CH, 3*CH2), 61.9 (CH), 107.9, 109.3, 111.3, 120.7, 121.1, 122.0 and
126.9 (7CH, Ar), 116.4, 122.3, 123.2, 133.9 и 140.4 (5 sp2 C), 182.1
(C=S). MS (EI, 70 eV), m/z (I, %): 339 [M]+ (59), 219 (32), 191 (100), 146
(30), 119 (9), 106 (30), 94 (28).
1
2
diffractometer [(MoK) 0.71072Å, ω-scans, 2<58], and 9347
=
independent reflections [Rint = 0.0431] were used in further refinement.
The structure was solved by direct method and refined by the full-matrix
least-squares technique against F2 in the anisotropic-isotropic
approximation. Hydrogen atoms of solvate water molecules were found
in difference Fourier synthesis, and the positions of others were
calculated. All hydrogen atoms were refined in the isotropic
approximation within the riding model. The refinement converged to wR2
= 0.1220 and GOF = 0.995 for all the independent reflections (R1 =
0.0441 was calculated against F for 7004 observed reflections with
I>2(I)). All calculations were performed using SHELXTL PLUS 5.0.30
CCDC 1886096 contains the supplementary crystallographic information
for 14.
8-Thioxo-5,6-dihydro-14aH-indeno[2,1-e]pyrrolo[2',1':3,4]pyrazino[2,1-
b][1,3]thiazin-9(8H)-one (3d): Brown solid, (159 mg, 49%), Rf = 0.21
(CH2Cl2). Mp = 297–298 °С. Found: C, 63.13; H, 3.56; N, 8.50. Anal.
calcd for C17H12N2OS2 (%): C, 62.94; H, 3.73; N, 8.63. IR νmax (KBr, cm–
1): 2954, 2923, 2853, 1594, 1466, 1440, 1399, 1356, 1355, 1314, 1272,
1152, 960, 875, 810, 788, 745, 729, 661, 507. 1H NMR (400 MHz, CDCl3,
δ, ppm, J/Hz): 3.89 (ddd, 1H, CH2, 1J = 13.8, 2J = 9.9, 3J = 4.2), 4.19-4.33
(m, 2H, CH2), 5.30 (ddd, 1H, CH2, 1J = 13.7, 2J = 3.5, 3J = 3.5), 6.27 (dd,
1H, ArH, 1J = 3.7, 2J = 2.7), 6.34 (dd, 1H, ArH, 1J = 3.7, 2J = 1.2), 6.38 (s,
1H, CH), 6.82 (dd, 1H, ArH, 1J = 2.7, 2J = 1.7), 7.32-7.35 (m, 1H, ArH),
7.47-7.53 (m, 2H, ArH), 7.60-7.64 (m, 1H, ArH). 13C NMR (50 MHz,
CDCl3, δ, ppm): 44.7 and 45.6 (both for 1СH, CH2CH2), 61.4 (CH), 108.6,
109.7, 121.9, 122.7, 123.2, 132.6 and 133.9 (7CH, Ar), 119.9, 127.7,
131.3, 138.3 and 163.2 (5 sp2 C), 186.4 (C=O), 188.2 (C=S). MS (EI, 70
eV), m/z (I, %): 324 [M]+ (53), 204 (14), 119 (100), 93 (67).
General procedure for the preparation of 1,3-thiazine-4-thiones in
3,4-dihydropyrrolo[1,2-a]pyrazine. The mixture of 1,2-dithiolo-3-thione
1a-i (1 mmol) and 3,4-dihydropyrrolo[1,2-a]pyrazine 2 (840 mg, 7 mmol)
was stirred at ca. 20 °C for the time given below and separated by
column chromatography (silica gel Merck 60, hexane/CH2Cl2 mixtures,
and then CH2Cl2).
5,6-Dihydro-8H,13aH-pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]benzothiazine-
8-thione (3a). Yellow solid, (174 mg, 64%), Rf = 0.2 (CH2Cl2/hexane,
50:50). Mp = 132–133 °С. Found: C, 61.70; H, 4.42; N, 10.30. Anal.
calcd for C14H12N2S2: C, 61.73; H, 4.44; N, 10.28%. IR νmax (KBr, cm–1):
2872 (CH2), 1588, 1448, 1436, 1396, 1308, 1260, 1224 (C=S), 1072, 932,
10,14,14-Trimethyl-5,6,13,14-tetrahydro-8H,15aH-pyrrolo[2'',1'':3',4']-
pyrazino[2',1':2,3][1,3]thiazino[6,5-c]quinoline-8-thione (3e). Yellow solid,
(147 mg, 40%), Rf = 0.36 (CH2Cl2). Mp = 192–193 °С. Found: C, 65.31;
H, 5.69; N, 11.37. Anal. calcd for C20H21N3S2 (%): C, 65.36; H, 5.76; N,
11.43. IR νmax (KBr, cm–1): 2960 and 2920 (CH), 1496, 1424, 1392, 1292,
1212, 1076, 936, 832, 720. 1H NMR (300 MHz, CDCl3, δ, ppm, J/Hz):
1.37, 1.47 and 2.28 (all three s, 9H, CH3), 3.35-3.50 (brs, 1H, NH), 4.11-
4.27 (m, 3H, CH2), 5.25-5.33 (m, 1H, CH2), 5.94 (s, 1H, CH), 6.24 (dd,
1
768, 712. H NMR (400 MHz, CDCl3, δ, ppm, J/Hz): 4.12 (ddd, 1H, CH2,
1J = 13.7, 2J = 9.8, 3J = 3.9), 4.23-4.36 (m, 2H, CH2), 5.43 (ddd, 1H, CH2,
1J = 13.9, 2J = 3.7, 3J = 3.4), 6.10 (s, 1H, CH), 6.24 (dd, 1H, ArH, 1J = 3.7,
1
2
2J = 2.7), 6.27-6.29 (m, 1H, ArH), 6.77 (dd, 1H, ArH, J = 2.7, J = 1.7),
1
2
3
7.26-7.32 (m, 2H, ArH), 7.38 (ddd, 1H, ArH, J = 7.9, J = 6.7, J = 1.5),
8.53 (dd, 1H, ArH, 1J = 7.8, 2J = 1.5). 13C NMR (50 MHz, CDCl3, δ, ppm):
44.4 and 48.7 (both for 1CH, CH2CH2), 59.4 (CH), 107.8, 109.3, 121.0,
126.2, 126.9, 131.4 and 135.2 (7 СH, Ar), 121.2, 134.1 и 135.1 (3 sp2 C),
193.6 (C=S). MS (EI, 70 eV), m/z (I, %): 272 [M]+ (100), 152 (63), 119
(25), 106 (64).
1
2
2
3
1H, ArH, J = 3.7, J = 2.7), 6.30 (ddd, 1H, ArH, 1J = 3.7, J = 1.5, J =
0.6), 6.55 (d, 1H, ArH, J = 8.0), 6.78 (dd, 1H, ArH, 1J = 2.6, 2J = 1.6),
6.88 (ddd, 1H, ArH, 1J = 8.0, 2J = 1.9, 3J = 0.5), 7.49 (d, 1H, ArH, J=1.8).
13C NMR (75 MHz, CDCl3, δ, ppm): 21.0 (CH3), 26.3 and 27.2 (both for
1СH, C(CH3)2), 44.7 and 46.3 (both for 1СH, CH2CH2), 56.4 (C(CH3)2),
59.7 (C-H), 108.1, 109.2, 115.3, 121.2, 128.3 and 128.8 (6CH, Ar), 120.9
123.2, 127.5, 131.1, 140.7 and 145.0 (6 sp2 C), 189.8(C=S). MS (EI, 70
eV), m/z (I, %): 367 [M]+ (7), 247 (10), 232 (100), 119 (17), 106 (21).
5,6-Dihydro-8H,13aH-pyrido[3,2-e]pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]-
thiazine-8-thione (3b). Yellow solid, (240 mg, 88%) Rf = 0.41 (CH2Cl2).
Mp = 130–131 °С. Found: C, 57.23; H, 4.16; N, 15.25. Anal. calcd for
C13H11N3S2 (%): C, 57.12; H, 4.06; N, 15.37. IR νmax (KBr, cm–1): 2930
(CH2), 1568, 1548, 1436, 1412, 1204, 1156, 1072, 940, 736, 516. 1H
NMR (300 MHz, CDCl3, δ, ppm, J/Hz): 4.03 (ddd, 1H, CH2, 1J = 13.9, 2J =
9.2, 3J = 4.7), 4.23-4.37 (m, 2H, CH2), 5.32 (ddd, 1H, CH2, 1J = 13.6, 2J =
3.7, 3J = 3.3), 6.21-6.26 (m, 2H, CH and ArH), 6.28-6.31 (m, 1H, ArH),
10,11,14,14-Tetramethyl-5,6,13,14-tetrahydro-8H,15aH-pyrrolo-
[2'',1'':3',4']pyrazino[2',1':2,3][1,3]thiazino[6,5-c]quinoline-8-thione
Yellow solid, (65 mg, 17%), Rf = 0.38 (CH2Cl2). Mp = 122–123 °С).
Found: C, 66.01; H, 6.12; N, 11.08. Anal. calcd for C21H23N3S2 (%): C,
66.10; H, 6.08; N, 11.01. IR νmax (KBr, cm–1): 2960, 2920 and 2860 (CH),
(3f).
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
1620, 1452, 1432, 1396, 1380, 1296, 1204, 1072, 932, 732, 716. 1H
NMR (300 MHz, CDCl3, δ, ppm, J/Hz): 1.36 and 1.44 (both s, 6H, 2*CH3),
2.17 (s, 6H, 2*CH3), 2.75-3.55 (brs, 1H, NH), 4.08-4.28 (m, 3H, CH2),
General procedure for the preparation of 1,3-thiazine-4-thiones
P(OMe)3. A mixture of pyrrolopyrazine 2 (1 mmol), 4-chloro-1,2-dithiole-
3-thione 1j-m (1 mmol) and P(OMe)3 (124 mg, 1 mmol) in MeCN (5 ml)
was refluxed by the time given below up to disappearance of starting
material (TLC control), evaporated by reduced pressure and separated
by column chromatography (silica gel Merck 60, hexane / CH2Cl2
mixtures, and then CH2Cl2).
1
5.21-5.32 (m, 1H, CH2), 5.91 (s, 1H, CH), 6.21 (dd, 1H, ArH, J = 3.7, 2J
= 2.7), 6.25-6.30 (m, 1H, ArH), 6.42 (s, 1H, ArH), 6.75 (dd, 1H, ArH, 1J =
2.6, 2J = 1.5), 7.41 (s, 1H, ArH). 13C NMR (75 MHz, CDCl3, δ, ppm): 19.2
and 19.9 (both for 1СH, 2*CH3), 26.3 and 27.2 (both for 1СH, C(CH3)2),
44.7 and 46.3 both for 1СH, CH2CH2), 56.3 (C(CH3)2), 59.7 (C-H), 108.0,
109.2, 116.7, 121.1 and 128.8 (5CH, Ar), 121.0, 121.1, 126.3, 131.1,
136.7, 141.0 and 143.8 (7 sp2 C), 189.9 (C=S). MS (EI, 70 eV), m/z
(I, %): 381 [M]+ (14), 261 (13), 246 (100), 119 (8), 106 (15).
3-Chloro-2-(pyrid-2-ylthio)-6,7-dihydro-4H,11bH-pyrrolo[2',1':3,4]-
pyrazino[2,1-b][1,3]thiazine-4-thione (3j). Yellow solid, (139 mg, 38%,
P(OMe)3), Rf = 0.21 (CH2Cl2). Mp = 140–141 °С. Found: C, 49.33; H,
3.35; N, 11.39. Anal. calcd for C15H12ClN3S3 (%): C, 49.23; H, 3.31; N,
11.48. IR νmax (KBr, cm–1): 2972 and 2912(CH), 1568, 1560, 1456, 1432,
1416, 1392, 1292, 1268, 1212, 1192, 1172, 1148, 1120, 1072, 932, 768,
(4-Nitrophenyl)(10,14,14-trimethyl-8-thioxo-5,6,8,14-tetrahydro-
13H,15aH-pyrrolo[2'',1'':3',4']pyrazino[2',1':2,3][1,3]thiazino[6,5-c]quinolin-
13-yl)methanone (3g). Yellow solid, (160 mg, 31%), Rf = 0.45 (CH2Cl2).
Mp = 256–257 °С. Found: C, 62.83; H, 4.72; N, 10.80. Anal. calcd for
C27H24N4O3S2 (%): C, 62.77; H, 4.68; N, 10.84. IR νmax (KBr, cm–1): 2972
and 2928 (CH), 1660 (C=O), 1524 (NO2), 1492, 1404, 1336(NO2), 1212,
932, 772, 736, 712. NMR 1H (300 MHz, CDCl3, δ, ppm, J/Hz): 1.47, 2.08
and 2.24 (all three s, 9H, CH3), 4.13 (ddd, 1H, CH2, 1J = 13.4, 2J = 7.9, 3J
= 5.9), 4.25-4.37 (m, 2H, CH2), 5.33 (ddd, 1H, CH2, 1J = 13.8, 2J = 3.9, 3J
1
748, 720. H NMR (300 MHz, CDCl3, δ, ppm, J/Hz): 3.84 (ddd, 1H, CH2,
1J = 13.9, 2J = 7.0, 3J = 7.0), 4.15-4.29 (m, 2H, CH2), 5.26 (ddd, 1H, CH2,
1J = 13.9, 2J = 3.2, 3J = 3.2), 6.13 (s, 1H, CH), 6.14-6.20 (m, 2H, ArH),
6.71-6.76 (m, 1H, ArH), 7.26 (t, 1H, ArH, J = 6.2), 7.51 (d, 1H, ArH, J =
8.1), 7.70 (t, 1H, ArH, J = 7.7), 8.56 (d, 1H, ArH, J = 4.8). 13C NMR (75
MHz, CDCl3, δ, ppm): 44.5 and 48.4 (both for 1СH, CH2CH2), 60.3 (CH),
108.4, 109.4, 121.5, 123.4, 127.7, 137.5 and 150.3 (7CH, Ar), 119.9,
124.6, 142.3 and 152.5 (4 sp2 C), 186.5 (C=S). MS (EI, 70 eV), m/z
(I, %): 367 [M+2]+ (11), 365 [M]+ (23), 330 [M-Cl]+ (14), 257 [M-
(2PyS)+2]+ (11), 255 [M-(2PyS)]+ (25), 247 (4), 245 (10), 210 (100), 137
(51), 135 (94), 119 (39).
2
= 3.7), 6.01 (s, 1H, CH), 6.25 (dd, 1H, ArH, 1J = 3.7, J = 2.2), 6.31-6.38
(m, 2H, ArH), 6.67 (dd, 1H, ArH, 1J = 8.1, 2J = 1.5), 6.82 (dd, 1H, ArH, 1J
= 2.9, 2J = 1.5), 7.45 (s, 1H, ArH), 7.68 and 8.08 (both d, 4H, p-C6H4NO2,
J=8.8). NMR 13C (75 MHz, CDCl3, δ, ppm): 21.2, 22.4 and 24.5(all three
for 1СH, 3*CH3), 44.7 and 46.5 (both for 1СH, CH2CH2), 60.1 (C-H), 63.2
(C(CH3)2), 108.5, 109.5, 121.6, 126.4, 128.1 and 128.3 (6CH, Ar), 123.5
and 130.9 both for 2CH, Ar), 120.2, 129.9, 130.8, 134.4, 135.1, 143.4,
148.7, 149.2, 168.8 (9 sp2 C), 189.5 (C=S). MS (EI, 70 eV), m/z (I, %):
516 [M]+ (3), 150 (34), 120 (30), 106 (51), 64 (100).
3-Chloro-2-(phenylthio)-6,7-dihydro-4H,11bH-pyrrolo[2',1':3,4]pyrazino-
[2,1-b][1,3]thiazine-4-thione (3k). Pale-brown solid, (164 mg, 45%,
P(OMe)3), Rf = 0.35 (CH2Cl2/hexane, 65:35). Mp = 142–143 °С. Found: C,
52.51; H, 3.82; N, 7.95. Anal. calcd for C16H13ClN2S3 (%): C, 52.66; H,
3.59; N, 7.68. IR νmax (KBr, cm–1): 2920 and 2868 (CH), 1722, 1652,
1460, 1440, 1380, 1271, 1205, 1172, 1073, 934, 746, 728, 688. 1H NMR
(300 MHz, CDCl3, δ, ppm, J/Hz): 3.79 (ddd, 1H, CH2, 1J = 13.9, 1J = 9.9,
1J = 4.0), 4.07-4.23 (m, 2H, CH2), 5.24 (ddd, 1H, CH2, 1J = 13.9, 2J = 3.1,
3J = 2.9), 6.11-6.16 (m, 3H, ArH), 6.70 (s, 1H, CH), 7.36-7.50 (m, 3H,
ArH), 7.57 (d, 2H, ArH, J = 7.3). 13C NMR (75 MHz, CDCl3, δ, ppm): 44.5
and 48.4 (both for 1СH, CH2CH2), 60.2 (CH), 108.3, 109.3, 121.5 and
131.0 (4CH, Ar), 129.5 and 136.3 (both for 2CH, Ar), 127.7, 119.8, 121.4
and 148.5 (4 sp2 C), 186.6 (C=S). MS (EI, 70 eV), m/z (I, %): 366 [M+2]+
(7), 364 [M]+ (13), 257 [M-PhS+2]+ (21), 255 [M-PhS]+ (53), 137
[C3ClS2+2]+ (53), 135 [C3ClS2]+ (100), 119 (31), 109 [PhS] (21).
2-Phenyl-6,7-dihydro-4H,11bH-pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]thiaz-
ine-4-thione (3h). Yellow solid, (137 mg, 46%), Rf = 0.24 (CH2Cl2/hexane,
50:50). Mp = 138–139 °С. Found: C, 64.35; H, 4.78; N, 9.35. Anal. calcd
for C16H14N2S2 (%): C, 64.39; H, 4.73; N, 9.39. IR νmax (KBr, cm–1): 2976,
2920 and 2860 (CH), 1552, 1488, 1448, 1408, 1344, 1320, 1220, 1160,
1076, 932, 752, 720. 1H NMR (400 MHz, CDCl3, δ, ppm, J/Hz): 3.89 (ddd,
1H, CH2, 1J = 13.7, 2J = 9.3, 3J = 4.9), 4.18-4.29 (m, 2H, CH2), 5.29 (ddd,
1H, CH2, 1J = 13.7, 2J = 3.4, 3J = 3.4), 6.20 (s, 1H, CH), 6.27 (dd, 1H,
1
2
1
ArH, J = 3.7, J = 3.7), 6.35-6.37 (m, 1H, ArH), 6.78 (dd, 1H, ArH, J =
2.7, 2J = 1.7), 7.39 (s, 1H, CH), 7.42-7.51 (m, 3H, ArH), 7.71-7.74 (m, 2H,
ArH). 13C NMR (50 MHz, CDCl3, δ, ppm): 44.6 and 46.6 (both for 1СH,
CH2CH2), 59.2 (CH), 107.9, 109.4, 121.2, 125.1 and 131.1 (5CH, Ar and
CH), 128.3 and 129.1 (both for 2CH, Ph), 120.7, 135.2 and 145.2 (3 sp2
C), 191.9 (C=S). MS (EI, 70 eV), m/z (I, %): 298 [M]+ (100), 178 (41), 119
(26), 106 (89), 77 [Ph]+ (17).
3-Chloro-2-phenoxy-6,7-dihydro-4H,11bH-pyrrolo[2',1':3,4]pyrazino[2,1-
b][1,3]thiazine-4-thione (3l). Pale-brown solid, (12 mg, 35%, P(OMe)3), Rf
= 0.25 (CH2Cl2/hexane, 65:35). Mp 66-68 °С. Found: C, 55.21; H, 3.82; N,
7.98. Anal. calcd for C16H13ClN2OS2 (%):C, 55.08; H, 3.76; N, 8.03. IR
νmax (KBr, cm–1): 2920 and 2869 (CH), 1519, 1484, 1381, 1218, 1192,
1168, 1072, 992, 881, 758, 730, 690. 1H NMR (300 MHz, CDCl3, δ, ppm,
J/Hz): 3.87 (ddd, 1H, CH2, J=13.8, 8.6, 5.5), 4.14-4.27 (m, 2H, CH2), 5.28
(ddd, 1H, CH2, J=13.8, 3.1, 2.9), 6.13-6.17 (m, 1H, Ar), 6.18-6.22 (m, 1H,
Ar), 6.34 (s, 1H, CH), 6.70-6.74 (m, 1H, ArH), 7.11 (d, 2H, Ar, J=7.3),
7.26 (d, 1H, ArH, J=7.3), 7.38 (t, 2H, ArH, J=7.3). 13C NMR (75 MHz,
CDCl3, δ, ppm): 44.6 and 48.5 (both for 1С, CH2CH2), 59.8 (CH), 108.4,
109.5, 121.6 and 126.6 (4CH, Ar), 120.4 and 129.9 (both for 2CH, Ar)
116.7, 119.6, 153.2 and 158.6 (4 sp2 C), 189.7 (C=S). MS (EI, 70 eV),
m/z (I, %): 350 [M+2]+ (16), 348 [M]+ (40), 273 [M-Ph+2]+ (11), 271 [M-
Ph]+ (29), 257 [M-PhO+2]+ (9), 255 [M-PhO]+ (20), 241 [M-Ph-S+2]+ (17),
239 [M-Ph-S]+ (47), 137 [C3ClS2+2]+ (42), 135 [C3ClS2]+ (100), 119 (63).
3-Phenyl-6,7-dihydro-4H,11bH-pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]thiaz-
ine-4-thione (3i). Pale-brown solid, (158 mg, 53%), Rf
= 0.53
(CH2Cl2/hexane, 65:35). Mp = 66–67 °С. Found: C, 64.43; H, 4.81; N,
9.35. Anal. calcd for C16H14N2S2 (%): C, 64.39; H, 4.73; N, 9.39. IR νmax
(KBr, cm–1): 3020, 2916 and 2868 (CH), 1528, 1488, 1436, 1388, 1320,
1300, 1208, 1168, 1072, 932, 812, 736, 696, 624. 1H NMR (300 MHz,
1
2
3
CDCl3, δ, ppm, J/Hz): 3.97 (ddd, 1H, CH2, J = 13.7, J = 8.3, J = 5.5),
4.18-4.30 (m, 2H, CH2), 5.30 (ddd, 1H, CH2, 1J = 13.7, 2J = 3.5, 3J = 3.5),
6.16 (s, 1H, CH), 6.27 (dd, 1H, ArH, 1J = 3.5, 2J = 2.9), 6.34 (dd, 1H, ArH,
1J = 3.7, 2J = 1.3), 6.79 (dd, 1H, ArH, 1J = 2.5, 2J = 1.7), 7.23 (s, 1H, CH),
7.31-7.42 (m, 5H, ArH). 13C NMR (75 MHz, CDCl3, δ, ppm): 44.7 and
47.1 (both for 1СH, CH2CH2), 59.6 (CH), 107.9, 109.3, 121.2, 127.5 and
128.7 (5CH, Ar and CH), 128.1 and 128.9 (both for 2CH, Ar) 121.0, 141.0
and 141.2 (3 sp2 C), 191.8 (C=S). MS (EI, 70 eV), m/z (I, %): 298 [M]+
(51), 265 [M-SH]+ (31), 177 (85), 119 (50), 106 (100).
3-Chloro-2-morpholin-4-yl-6,7-dihydro-4H,11bH-pyrrolo[2',1':3,4]-
pyrazino[2,1-b][1,3]thiazine-4-thione (3m). Orange solid, (99 mg, 29%,
P(OMe)3), Rf = 0.16 (CH2Cl2/acetone, 99:1). Mp 232-233 °С. Found: C,
49.21; H, 4.98; N, 12.08. Anal. calcd for C14H16ClN3OS2 (%): C, 49.18; H,
4.72; N, 12.29. IR νmax (KBr, cm–1): 2964, 2919 and 2861 (CH), 1512,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
1438, 1421, 1342, 1320, 1309, 1288, 1256, 1110, 1060, 994, 985, 888,
722. 1H NMR (300 MHz, DMSO-d6, δ, ppm, J/Hz): 3.41-3.72 (m, 6H,
CH2), 3.74-3.85 (m, 3H, CH2), 3.92-4.07 (m, 1H, CH2), 4.16-4.33 (m, 2H,
CH2), 6.07-6.11 (m, 1H, ArH), 6.11-6.14 (m, 1H, ArH), 6.46 (s, 1H, CH),
6.85-6.90 (m, 1H, ArH). 13C NMR (75 MHz, DMSO-d6, δ, ppm): 43.9,
44.1, 49.9 and 50.8 (4СH, 4*NCH2), 59.3 (CH), 66.1 (2CH, OCH2) 106.3,
108.3 and 120.9 (3CH, Ar), 109.2, 120.7 and 156.5 (3 sp2 C), 198.0
(C=S). MS, m/z (%): 343 [M+2]+ (20), 341 [M]+ (48), 307 [M-Cl]+ (12), 223
(43), 221 (100), 119 (48).
9-Ethyl-10-thioxo-5,6-dihydro-8H,9H,10H,14aH-[1,2]dithiolo[4',3':5,6]-
[1,4]thiazino[3,2-e]pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]thiazin-8-one (11).
Red solid, (193 mg, 45%), 3 h, Rf = 0.42 (CH2Cl2/acetone, 98:2). Mp =
120–121 °С. Found: C, 43.90; H, 3.51; N, 10.12. Anal. calcd for
C15H13N3OS5 (%):C, 43.77; H, 3.18; N, 10.21. IR νmax (KBr, cm–1): 2958,
2922 and 2876 (CH), 1641, 1469, 1455, 1445, 1433, 1380, 1355, 1340,
1279, 1206, 1194, 1083, 1074, 977, 933, 758, 732. 1H NMR (300 MHz,
CDCl3, δ, ppm, J/Hz): 1.30 (t, 3H, CH2CH3, J = 7.1), 3.33 and 4.41 (both
dq, 2H, CH2CH3, 1J = 14.5, 2J = 7.3), 3.46 (ddd, 1H, CH2, 1J = 13.4, 2J =
3
1
2
8.8, J = 5.0), 4.05-4.20 (m, 2H, CH2), 4.58 (dt, 1H, CH2, J = 13.3, J =
3.1), 6.15-6.22 (m, 1H, ArH), 6.23-6.27 (m, 1H, ArH), 6.32 (s, 1H, CH),
6.67-6.76 (m, 1H, ArH). 13C NMR (75 MHz, CDCl3, δ, ppm): 17.4
(CH2CH3), 39.4, 40.0 and 44.5 (3CH, NCH2), 59.5 (CH), 107.5, 109.2 and
121.1 (3CH, Ar), 116.2, 121.0, 131.9, 138.7 and 140.5 (5 sp2 C), 159.2
(C=O), 196.5 (C=S). MS (EI, 70 eV), m/z (I, %): 379 [M-S]+ (74), 291 (12),
259 (65), 231 (34), 119 (100).
General procedure for the preparation of 1,3-thiazine-4-ones The
mixture of 1,2-dithiolo-3-one (1 mmol), Ph3P (262 mg, 1 mmol) and 3,4-
dihydropyrrolo[1,2-a]pyrazine 2 (120 mg, 1 mmol) in benzene (5 ml) was
stirred at room temperature for the time given below up to disappearance
of starting material (TLC control), evaporated by reduced pressure and
separated by column chromatography (silica gel Merck 60, hexane /
CH2Cl2 mixtures, and then CH2Cl2).
Dimethyl
2-(9-ethyl-8-oxo-11-thioxo-5,6-dihydro-8H,9H,13aH-pyrrolo-
[2',1':3,4]pyrazino[2,1-b][1,4]thiazino[3,2-e][1,3]thiazin-10(11H)-ylidene)-
1,3-dithiole-4,5-dicarboxylate (13). Dark red solid, (365 mg, 66%), 3 h, Rf
= 0.38 (CH2Cl2/acetone, 98:2). Mp = 187–188 °С. Found: C, 45.63; H,
3.54; N, 7.52. Anal. calcd for C21H19N3O5S5 (%): C, 45.55; H, 3.46; N,
7.59. IR νmax (KBr, cm–1): 2948 and 2868 (CH), 1740 и 1728 (C=O(O)),
1640 (C=O(N)), 1428, 1416, 1376, 1360, 1328, 1248, 1100, 992, 760,
732, 700, 484, 472. 1H NMR (300 MHz, CDCl3, δ, ppm, J/Hz): 1.26 (t, 3H,
5,6-Dihydro-8H,13aH-pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]benzothiazine-
8-one (9a). Colorless solid, (223 mg, 87%), 3 h, Rf = 0.12 (CH2Cl2). Mp =
155–156 °С. Found: C, 65.53; H, 4.42; N, 10.70. Anal. calcd for
C14H12N2OS (%): C, 65.60; H, 4.72; N, 10.93. IR νmax (KBr, cm–1): 2923,
2880, 1639, 1587, 1445, 1389, 1364, 1335, 1274, 1235, 1191, 1074, 939,
794, 752, 709, 701, 605, 486, 407. 1H NMR (300 MHz, CDCl3, δ, ppm,
J/Hz): 3.53 (ddd, 1H, CH2, 1J = 13.6, 2J = 9.0, 3J = 5.0), 4.14-4.25 (m, 2H,
CH2), 4.74 (ddd, 1H, CH2, 1J = 13.2, 2J = 3.3, 3J = 3.4), 6.21-6.25 (m, 2H,
ArH), 6.36 (s, 1H, CH), 6.70-6.72 (m, 1H, ArH), 7.27-7.34 (m, 2H, ArH),
7.38-7.43 (m, 1H, ArH), 8.13-8.17 (m, 1H, ArH). 13C NMR (75 MHz,
CDCl3, δ, ppm): 40.2 and 44.7 (both for 1СH, CH2CH2), 56.7 (CH), 107.0,
109.2, 120.8, 126.4, 127.2, 131.1 and 132.1 (7СH, Ar), 121.8, 128.7 and
137.4 (3 sp2 C), 165.0 (C=O). MS (EI, 70 eV), m/z (I, %): 256 [M]+ (13),
135 (57), 136 (34), 120 (100).
1
CH2CH3, J = 7.1), 3.18 and 3.27 (both dqw, 2H, CH2CH3, J = 14.0, 2J =
7.1), 3.48 (ddd, 1H, CH2, 1J = 13.7, 2J = 9.6, 3J = 4.3), 3.91 and 3.93
1
(both s, 6H, Me), 4.05-4.20 (m, 2H, CH2), 4.59 (ddd, 1H, CH2, J = 13.2,
2J = 3.2, 3J = 3.2), 6.20 (dd, 1H, ArH, 1J = 3.6, 2J = 2.7), 6.27 (dd, 1H,
ArH, 1J = 3.8, 2J = 1.7), 6.44 (s, 1H, CH), 6.71 (dd, 1H, ArH, 1J = 2.7, 2J =
1.6). 13C NMR (75 MHz, CDCl3, δ, ppm): 13.8 (CH2CH3), 40.4, 44.8 and
48.4 (3CH, NCH2), 53.6 and 53.8 (2CH, 2*OCH3), 58.2 (CH), 107.6,
109.4 and 121.5 (3CH, Ar), 120.3, 128.0, 132.5, 133.6, 135.3, 140.3,
159.7, 160.0, 161.1 and 161.5 (10 sp2 C), 196.0 (C=S). MS (EI, 70 eV),
m/z (I, %): 553 [M]+ (4), 433 (14), 404 (23), 376 (25), 274 (66), 152 (40),
119 (100).
5,6-Dihydro-8H,13aH-pyrido[3,2-e]pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]-
thiazin-8-one (9b). Colorless solid, (252 mg, 98%), 3 h, Rf = 0.42
(CH2Cl2/acetone, 95:5). Mp = 143–144 °С. Found: C, 60.33; H, 4.16; N,
16.25. Anal. calcd for C13H11N3OS (%): C, 60.68; H, 4.31; N, 16.33. IR
νmax (KBr, cm–1): 2933 and 2887(CH), 1640, 1573, 1450, 1398, 1333,
1281, 1193, 1171, 1144, 1081, 763, 727, 644, 608, 496. 1H NMR (300
Synthesis
of
dimethyl
2-(9-ethyl-8-oxo-11-thioxo-5,6-dihydro-
8H,9H,13aH-pyrrolo[2',1':3,4]pyrazino[2,1-b][1,4]thiazino[3,2-e][1,3]-
thiazin-10(11H)-ylidene)-1,3-dithiole-4,5-dicarboxylate (13) from dimethyl
2-(4-ethyl-3-oxo-6-thioxo-3H,4H-[1,2]dithiolo[3,4-b][1,4]thiazin-5(6H)-
ylidene)-1,3-dithiole-4,5-dicarboxylate (11). A mixture of 1,2-dithiole-3-
thione 11 (465 mg, 1 mmol), DMAD (142 mg, 1 mmol) and Yb(OTf)3 (124
mg, 0.2 mmol) in CH2Cl2 (20 ml) was stirred at room temperature for 0.5
h, evaporated by reduced pressure and separated by column
chromatography (silica gel Merck 60, hexane/CH2Cl2 mixtures, and then
CH2Cl2). Yield 13: 404 mg, 73%.
2
3
MHz, CDCl3, δ, ppm, J/Hz): 3.54 (ddd, 1H, CH2, 1J = 13.7, J = 8.2, J =
6.1), 4.16-4.27 (m, 2H, CH2), 4.70 (ddd, 1H, CH2, 1J = 13.2, 2J = 3.3, 3J =
3.3), 6.22-6.24 (m, 1H, ArH), 6.27-6.29 (m, 1H, ArH), 6.49 (s, 1H, CH),
2
6.71-6.74 (m, 1H, ArH), 7.24 (dd, 1H, ArH, 1J = 7.7, J = 4.8), 8.38 (dd,
1H, ArH, 1J = 7.8, 2J = 2.0), 8.55 (dd, 1H, ArH, 1J = 4.8, 2J = 2.2). 13C
NMR (75 MHz, CDCl3, δ, ppm): 40.5 and 44.5 (both for 1СH, CH2CH2),
56.0 (CH), 107.2, 109.3, 121.0, 121.2, 138.4 and 152.4 (6CH, Ar), 120.8,
125.0 and 159.7 (3 sp2 C), 164.4 (C=O). MS (EI, 70 eV), m/z (I, %):
257[M]+ (34), 138 (8), 137 (6), 119 (100), 93 (36).
9-Ethyl-10-thioxo-5,6,9,10-tetrahydro-8H,13aH-[1,2]dithiolo[3',4':4,5]-
pyrrolo[2,3-e]pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]thiazin-8-one (14).
2-Phenyl-6,7-dihydro-4H,11bH-pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]-
thiazin-4-one (9c). Colorless solid, (254 mg, 90%), 2 h, Rf = 0.12
(CH2Cl2/acetone, 99:1). Mp = 92 °С (under argon). Found: C, 68.31; H,
4.89; N, 9.85. Anal. calcd for C16H14N2OS (%): C, 68.06; H, 5.00; N, 9.92.
IR νmax (KBr, cm–1): 2922, 2869, 1639, 1489, 1445, 1390, 1332, 1277,
1230, 1050, 764, 721. 1H NMR (300 MHz, CDCl3, δ, ppm, J/Hz): 3.42
(ddd, 1H, CH2, 1J = 13.5, 2J = 8.2, 3J = 5.9), 4.08-4.18 (m, 2H, CH2), 4.58
(ddd, 1H, CH2, 1J = 13.1, 2J = 3.2, 3J = 3.2), 6.21-6.26 (m, 1H, ArH), 6.29-
6.34 (m, 1H, ArH), 6.36 (s, 1H, CH), 6.56 (s, 1H, CH), 6.70-6.74 (m, 1H,
ArH) 7.38-7.48 (m, 3H, ArH) 7.64-7.70 (m, 2H, ArH). 13C NMR (75 MHz,
CDCl3, δ, ppm): 39.4 and 44.8 (both for 1СH, CH2CH2), 57.2 (CH), 107.1,
109.2, 115.7, 121.0 and 130.9 (5CH, Ar or CH), 127.9 and 128.9 (both
for 2CH, Ar), 121.2, 135.7 and 153.2 (3 sp2 C), 166.0 (C=S). MS (EI, 70
eV), m/z (I, %): 282 [M]+ (17), 134 (40), 120 (100), 77 [Ph]+ (26).
A) From 9-ethyl-10-thioxo-5,6-dihydro-8H,9H,10H,14aH-[1,2]dithiolo-
[4',3':5,6][1,4]thiazino[3,2-e]pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]thiazin-8-
one (11). A solution of thiazine 11 (0.1 mmol, 41 mg) in benzene (2 ml)
was stirred at room temperature for 4 days up to disappearance of
starting material (TLC control), evaporated by reduced pressure and
separated by column chromatography (silica gel Merck 60,
hexane/CH2Cl2 mixtures, and then CH2Cl2). Orange solid, (36 mg, 95%),
Rf = 0.13 (CH2Cl2/hexane, 50:50). Mp = 180–181 °С. Found: C, 47.83; H,
3.52; N, 10.81. Anal. calcd. for C15H13N3OS4 (%): C, 47.47; H, 3.45; N,
11.07. IR νmax (KBr, cm–1): 2924 and 2880(CH), 1632(C=O(N)), 1452,
1436, 1368, 1336, 1296, 1092, 1028, 756, 724. 1H NMR (400 MHz,
CDCl3, δ, ppm, J/Hz): 1.48 (t, 3H, CH2CH3, J=7.0), 3.61 (ddd, 1H, CH2, 1J
= 13.4, 2J = 8.0, 3J = 5.6), 4.20-4.24 (m, 2H, CH2), 4.59 (dt, 1H, CH2, 1J =
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
2
2
13.3, J = 3.6), 5.04 and 5.25 (both dq, for 1H, CH2CH3, 1J = 13.4, J =
137.5, 138.7 and 141.4 (5 sp2 C), 159.2 (C=O), 196.2 (C=S). MS (EI, 70
eV), m/z (I, %): 378 [M]+(64), 259 (100), 231 (43), 118 (56), 77 [Ph]+(60).
7.0), 6.24 (dd, 1H, ArH, 1J = 3.8, 2J = 2.7), 6.29 (dd, 1H, ArH, 1J = 3.7, 2J
= 1.6), 6.48 (s, 1H, CH), 6.74 (dd, 1H, ArH, J = 2.6, J = 1.7). 13C NMR
(75 MHz, CDCl3, δ, ppm): 17.5 (CH2CH3), 39.6, 40.1 and 44.7 (3CH,
NCH2), 59.8 (CH), 107.7, 109.4 and 121.2 (3CH, Ar), 116.4, 121.2, 132.1,
138.9 and 140.7 (5 sp2 C), 159.3 (C=O), 196.6 (C=S). MS (EI, 70 eV),
m/z (I, %): 379 [M]+ (20), 259 (27), 231 (20), 119 (100).
1
2
Acknowledgements
We gratefully acknowledge financial support from the Ministry of
Education and Science of the Russian Federation (grant no.
4.9651.2017/BP). The contribution of the Center for Molecular
Composition Studies of INEOS RAS is gratefully acknowledged.
Authors are grateful to Professor Kh. S. Shikhaliev for the
generous gift of 1,2-dithiole-3-thiones 1e-g.
B) From 4-ethyl-5-thioxo-4,5-dihydro-3H-bis([1,2]dithiolo)[4,3-b:3',4'-d]-
pyrrol-3-one (15). A mixture of pyrrolopyrazine 2 (120 mg, 1 mmol) and
4-ethyl-5-thioxo-4,5-dihydro-3H-bis([1,2]dithiolo)[4,3-b:3',4'-d]pyrrol-3-one
15 (291 mg, 1 mmol) in benzene (5 ml) was stirred for 3 h up to
disappearance of starting material (TLC control), evaporated by reduced
pressure and separated by column chromatography (silica gel Merck 60,
hexane / CH2Cl2 mixtures, and then CH2Cl2). Yield 13: 284 mg, 75%.
Keywords: 1,2-dithiole-3-thiones (3-ones); 3,4-
dihydropyrrolo[1,2-а]pyrazine; cyclic imines; substitution
reaction; thiazino[3,2-a]pyrazine-4(11bH)-(thi)ones
C) From 4-ethyl-5-thioxo-3H,4H,5H-bis([1,2]dithiolo)[3,4-b:4',3'-e][1,4]-
thiazin-3-one (10). A mixture of pyrrolopyrazine 2 (120 mg, 1 mmol) and
4-ethyl-5-thioxo-3H,4H,5H-bis([1,2]dithiolo)[3,4-b:4',3'-e][1,4]thiazin-3-
one 9 (323 mg, 1 mmol) in benzene (5 ml) was refluxed for 3 h up to
disappearance of starting material (TLC control), evaporated by reduced
pressure and separated by column chromatography (silica gel Merck 60,
hexane/CH2Cl2 mixtures, and then CH2Cl2). Yield 13: 212 mg, 56%.
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Synthesis of 10-thioxo-9-ethyl-5,6,12,13-tetrahydro-8H,10H,19aH,20aH-
pyrrolo [2''',1''':3'',4'']pyrazino[2'',1'':2',3'][1.3]thiazino[6',5':4,5]pyrrolo[3,2-
e]pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]thiazine-8-one (16). A solution of 9-
ethyl-10-thioxo-5,6-dihydro-8H,9H,10H,14aH-[1,2]dithiolo[4',3':5,6][1,4]-
thiazino[3,2-e]pyrrolo[2',1':3,4]pyrazino[2,1-b][1,3]thiazin-8-one 11 (379
mg, 1 mmol) in pyrrolopyrazine 2 (840 mg, 7 mmol) was stirred at room
temperature for 4 days up to disappearance of starting material (TLC
control), evaporated by reduced pressure and separated by column
chromatography (silica gel Merck 60, hexane/CH2Cl2 mixtures, and then
CH2Cl2). Yellow solid, (346 mg, 74%), Rf = 0.31 (CH2Cl2). Mp = 154–
155 °С. Found: C, 56.86; H, 4.34; N, 14.72. Anal. calcd for C22H21N5OS3
(%): C, 56.51; H, 4.53; N, 14.98. IR νmax (KBr, cm–1): 2961, 2924 and
2868, 1645, 1448, 1436, 1404, 1359, 1339, 1280, 1229, 1198, 1159,
1071, 932, 720. NMR 1H (300 MHz, CDCl3, δ, ppm, J/Hz): 1.48 (t, 3H,
CH2CH3, J = 7.0), 3.64 and 5.45 (both dq, 2H, CH2CH3, 1J = 13.5, 2J =
6.7), 4.14-4.27 (m, 5H, CH2), 4.48 (dq, 1H, CH2, 1J = 13.6, 2J = 3.7),
5.08-5.19 (m, 2H, CH2), 6.08 and 6.37 (both s, 2H, CH), 6.19-6.21 (m, 2H,
ArH), 6.23-6.27 (m, 2H, ArH), 6.67-6.72 (m, 1H, ArH), 6.73-6.75 (m, 1H,
ArH). NMR 13C (75 MHz, CDCl3, δ, ppm): 17.0 (CH2CH3), 39.8, 42.1,
44.7, 44.8 and 46.3 (5CH, 5*NCH2), 58.6 and 61.7 (2CH, 2*CH), 107.3,
108.0, 109.2 and 109.4 (all for 1CH, Ar), 120.9 (2CH, Ar), 118.3, 120.2,
121.7, 121.8, 125.2 and 132.7 (6 sp2 C), 159.1 (C=O), 181.3 (C=S). MS
(EI, 70 eV), m/z (I, %): 347 (2), 227 (33), 119 (100).
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starting material (TLC control), evaporated by reduced pressure and
separated by column chromatography (silica gel Merck 60,
hexane/CH2Cl2 mixtures, and then CH2Cl2). Yellow solid, (204 mg, 54%),
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Anal. calcd for C16H14N2OS4 (%): C, 50.76; H, 3.73; N, 7.40. IR νmax (KBr,
cm–1): 2924(CH), 1636(C=O(N)), 1464, 1428, 1380, 1288, 1232, 1212,
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1
CH2CH3, J = 7.0, 2J = 1.5), 5.76 (s, 1H, CH), 7.31 (s, 5H, Ph). NMR 13
C
(75 MHz, CDCl3, δ, ppm): 17.4 (CH2CH3), 35.3 and 39.4 (2CH, NCH2 and
NCH3), 66.6 (CH), 126.5, 128.9 and 129.1 (5CH, Ph), 111.6, 132.1,
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Vladimir A Ogurtsov, graduated from D. I. Mendeleev University of Chemical Technology of Russia in 1981. He
obtained his PhD degree in 1986 at the N.D. Zelinsky Institute of Organic Chemistry under supervision of Professor
Lenor. I. Khmelnitskii. His current research is focused on the synthesis and reactivity of sulfur heterocycles.
Yury V. Karpychev, graduated from Nizhny Novgorod State Technical University, Dzerzhinsk Polytechnical
Institute in 2005. He obtained his PhD degree in 2012 at the N.D. Zelinsky Institute of Organic Chemistry under
supervision of Professor Oleg. A. Rakitin. From 2012 he is working as a Head of the laboratory at JSC State
Scientific Research Institute “Kristall”, Dzerzhinsk. His current research is focused on the synthesis of nitrogen
heterocycles.
Panayiotis A. Koutentis (CSci, CChem, FRSC) was born in Bristol (UK) (1969) and obtained his BSc (1992)
and PhD (1997) at Imperial College (London, UK) working under the supervision of the late Prof. Charles W.
Rees (FRS, CBE). This was followed by a short stay with Prof. Roger Alder, (Bristol, 1997), and then
postdoctoral work with Prof. Fred Wudl (UCLA, 1997-8), and with Prof. Robert Haddon (Lexington, Kentucky,
1999). In 1999, Prof. Koutentis was appointed Lecturer at the University of Cyprus and in 2009 achieved
tenure; from 2015 he is Professor at the Department of Chemistry, University of Cyprus, Nicosia. His research
interests are synthesis, chemistry and application of rare heterocycles extending to the fields of medicinal and
materials chemistry.
Dr. Habil. Yulia V. Nelyubina is Head of the Center for molecular composition studies at A.N. Nesmeyanov
Institute of Organoelement Compounds (INEOS RAS). After graduating from the Higher Chemical College of
Russian Academic of Sciences (2008), she obtained her Ph.D. degree (2009) and then Dr. Habil. degree (2018)
at INEOS RAS. She has an expertise in X-ray diffraction analysis, including detailed studies of electron density
distribution in crystals, and her scientific interests cover the search for new “structure-property” relations and
their use in rational design of new molecular materials, e.g., in molecular spintronics.
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10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
Petr V. Primakov is an undergraduate student at Moscow State University. In 2018, he started his journey
into X-ray diffraction analysis under the supervision of Dr. Habil. Yulia V. Nelyubina. His current research is
focused on coordination compounds, including metal-organic frameworks, and their synthesis by using 3D-
printing technologies.
Oleg A. Rakitin (FRSC) was born in 1952, in Moscow (Russia). He received his PhD in 1980 and his D. Science
degree in 1992 and the Professor title in 2009 at the N.D. Zelinsky Institute of Organic Chemistry, where he is
working as a Head of the laboratory of polysulfur-nitrogen heterocycles. His professional interests include
chemistry of heterocyclic compounds, especially sulfur-nitrogen heterocycles and chemistry of materials.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900142
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
Introduction
Nitrogen-Sulfur Heterocycles
Results and discussion
Conclusions
Vladimir A. Ogurtsov, Yury V.
Karpychev, Yulia V. Nelyubina,
Petr V. Primakov, Panayiotis A.
Koutentis, and Oleg A. Rakitin*
Experimental section
Acknowledgments
References
Page No.–Page No.
Synthesis
of
6,7-
dihydropyrrolo[2,1-
c][1,3]thiazino[3,2-a]pyrazine-
4(11bH)-(thi)ones from 1,2-
dithiolo-3-(thi)ones
Both monocyclic and fused 1,2-di-thiolo-3-(thi)ones underwent addition of 3,4-dihydropyrrolo[1,2-а]pyrazine with selective extrusion
of S2 atom and formation of 6,7-dihydropyrrolo[2,1-c][1,3]thi-azino[3,2-a]pyrazine-4(11bH)-(thi)ones. 1,2-Dithiolo-3-one moiety was
found more reactive than the corresponding 1,2-dithiole-3-thione one.
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