1,3-Dipolar cycloaddition of 3-alkylsulfanyl-2-arylazo-3-(tert-cycloalkylamino)acrylonitriles with N-methyl- and N-phenylmaleimides

Article abstract of DOI:10.1016/j.tet.2014.12.087

A series of 1,2-diaza-1,3-butadienes with terminal S,N-acetal function were obtained and reacted with N-methyl- and N-phenylmaleimides. As a result of the 1,3-dipolar cycloaddition, a range of new functionalized nonaromatic heterocyclic compounds including: octahydro-1H-pyrrolo[3,4-a]indolizine, octahydropyrrolo[3′,4′:3,4]pyrrolo[1,2-a]azepine, hexahydropyrrolo[3′,4′:3,4]pyrrolo[2,1-c][1,4]oxazine and -thiazine, were obtained with good yields in mild conditions. Experimental and theoretic results allowed establishment of a relationship between the structures of the tert-cycloalkylamine group and the activity of the azomethine ylides generated.

Full text of DOI:10.1016/j.tet.2014.12.087

Accepted Manuscript
1,3-Dipolar cycloaddition of 3-alkylsulfanyl-2-arylazo-3-(tert-
cycloalkylamino)acrylonitriles with N-methyl- and N-phenylmaleimides
Nataliya P. Belskaya, Svetlana G. Lesogorova, Julia O. Subbotina, Aleksandr V.
Koksharov, Pavel A. Slepukhin, Wim Dehaen, Vasiliy A. Bakulev
PII:
S0040-4020(14)01803-1
10.1016/j.tet.2014.12.087
TET 26308
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 18 October 2014
Revised Date: 10 December 2014
Accepted Date: 23 December 2014
Please cite this article as: Belskaya NP, Lesogorova SG, Subbotina JO, Koksharov AV, Slepukhin
PA, Dehaen W, Bakulev VA, 1,3-Dipolar cycloaddition of 3-alkylsulfanyl-2-arylazo-3-(tert-
cycloalkylamino)acrylonitriles with N-methyl- and N-phenylmaleimides, Tetrahedron (2015), doi:
10.1016/j.tet.2014.12.087.
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2
,3-Dipolar cycloaddition of 3-alkylsulfanyl-
-aryazo-3-(tert-cycloalkylamino)acrylo-
Leave this area blank for abstract info.
nitriles with N-methyl- and N-
phenylmaleimides
Nataliya P. Belskaya, Svetlana G. Lesogorova, Julia O. Subbotina, Aleksandr V. Koksharov, Pavel A.
Slepukhin, Wim Dehaen and Vasiliy A. Bakulev
Ural Federal University, Mira Str. 19, Ekaterinburg 620002, Russia; Institute of Organic Synthesis of the Ural Branch of Russian Academy of Sciences, S.
Kovalevskaya Str. 20, Ekaterinburg 620219, Russia; Department of Chemistry, K.U. Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium

3
ACCEPTED MANUSCRIPT
1
,3-Dipolar cycloaddition of 3-alkylsulfanyl-2-arylazo-3-(tert-
cycloalkylamino)acrylonitriles with N-methyl- and N-phenylmaleimides
a
a
a
a
Nataliya P. Belskaya ∗ , Svetlana G. Lesogorova , Julia O. Subbotina , Aleksandr V. Koksharov , Pavel A.
b
c
a
Slepukhin , Wim Dehaen and Vasiliy A. Bakulev
a
Urals Federal University, Mira Str. 19, Ekaterinburg 620002, Russia
b
I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of Russian Academy of Sciences, S. Kovalevskaya Str. 20, Ekaterinburg 620219, Russia
Department of Chemistry, K.U. Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium
c
ABSTRACT
A series of 1,2-diaza-1,3-butadienes with terminal S,N-acetal function were obtained and reacted with N-methyl- and N-phenylmaleimides. As a
result of the 1,3-dipolar cycloaddition, a range of new functionalized nonaromatic heterocyclic compounds including: octahydro-1H-pyrrolo[3,4-
a]indolizine, octahydropyrrolo[3',4':3,4]pyrrolo[1,2-a]azepine, hexahydropyrrolo [3',4':3,4]pyrrolo[2,1-c][1,4]oxazine and -thiazine, were obtained
with good yields in mild conditions. Experimental and theoretic results allowed establishment of a relationship between the structures of the tert-
cycloalkylamine group and the activity of the azomethine ylides generated.
Keywords:
Diazadiene
S,N-acetal
Cycloaddition
Maleimide
Azomethine ylide
1
. Introduction
It is known that intramolecular [3+2]-cycloaddition of azomethine ylides is a powerful tool to construct various nitrogen-
1
containing cyclic systems from relatively simple precursors. Among the heterocycles targeted by azomethine ylide cycloaddition
1d,2
methods the most popular are substituted pyrrolidines, dihydropyrroles and pyrroles.
To construct the heterocyclic systems with more complicated ring frameworks it is necessary to select precursors containing
3
various functional groups, and enriched with double bonds and cyclic fragments. A direct strategy to achieve this purpose is the
employment of cyclic azomethine ylide moieties. The most known and widely described examples of azomethine ylides of this type
were generated from nitrogen-containing five-membered saturated heterocycles, such as proline and 1,3-thiazolidin-4-carboxylic
acid. Six-membered tert-cycloalkylamines most commonly utilized as substrates for the formation of this type of 1,3-dipole are
oxazin-2-one and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid. Piperidine-2-carboxylic acid is a less applied reagent. However,
not every route available for generation of linear azomethine ylides is also suitable for their cyclic analogues.
A traditional and widely spread method for the generation of azomethine ylides is the reaction of aldehydes and ketones with tert-
4
cycloalkylamines, first proposed by R. Grigg. Electron withdrawing groups usually are included into the structure of the starting
amines for the stabilization of the formed 1,3-dipole, such as: esters, carboxy- and carbonyl groups at the 2-position of morpholine
3e
and at the 2-position of pyrrolidine. This approach to cycloaddition was characterized by moderate yields and showed little exo/endo
3e,4b,5
selectivity.
On the other hand, examples of the azomethine ylides obtained from unsubstituted pyrrolidine, piperidine,
morpholine and, especially, azepine and thiomorpholine are more rare. The all abovementioned limitations of the known method for
the formation of azomethine ylides prompted a search for new sources and new methods to generate the cyclic analogs. An important
reason to develop new convenient routes to azomethine ylides, especially from tert-cycloalkyl amines, is the synthesis of nitrogen-
6
containing nonaromatic heterocycles, that composed the key core motif of natural alkaloids. New synthetic strategies for the
construction of pyrrolizidines, indolizidines and their structural analogous scaffolds are of importance to many areas of
pharmaceutical and biological research.
7
In this way, F. Laduron and H. G. Viehe have reported on the generation of trifluoromethyl azomethine ylides either by heating
α-trifluoromethyl thioaminals or by deprotonating trifluoromethyl thioamidium salts.
An original method for the generation of the azomethine ylides, is based on simultaneous formation of a cyclic fragment and a
8
dipolar moiety. Nonstabilized azomethine ylides have been formed from (2-azaallyl)stannanes and (2-azaallyl)silanes through an
intramolecular N-alkylation/demetallation cascade. The resulting ylides undergo intramolecular [3+2]-cycloaddition with
dipolarophiles to afford bicyclic or tricyclic products in good yield as 1:1 mixtures of exo- and endo-diastereomeres.
O-Methylation of α-hydroxy lactams, followed by treatment with cesium fluoride in the presence of methyl acrylate gave a
9
bicyclic adduct intermediate in the synthesis of (±)-retronecine and (±)-indicine. However, other imidate ylide cycloadditions were
10
proved to be inconsistent, and exhibited low yields.
11
In preliminary communications, we have shown that 1,2-diaza-1,4-butadienes 1 with alkylthio- and tert-aminogroups at the
terminal carbon atom are new convenient and available reagents, that rather easily and in mild conditions are able to generate
azomethine ylides. As a result of [3+2]-cycloaddition reactions between these compounds and N-methyl- and N-phenylmaleimides
2
a,b we have synthesized a new tricyclic derivatives 3,4 which can be considered as a synthetic analogues of natural alkaloids of the
pyrrolizidine type (Scheme 1).
∗
Belskaya Nataliya. Tel.: +7-922-60-3495; fax: +7-375-41-35; e-mail: n.p.belskaya@urfu.ru

4
ACCEPTED MANUSCRIPT
Scheme 1. Reaction of 3-alkylsulfanyl-2-arylazo-(3-pyrrolidin-1-yl)-acrylonitriles 1 with N-methyl- and N-phenylmaleimides 2a,b.
The aim of the current work was to estimate the scope and limitations of the transformation of 1,2-diaza-1,3-butadienes,
containing a terminal S,N-acetal function, to 1,3-dipoles, and to establish the relationship between the structure of the tert-
cycloalkylaminogroup (ring size and amount or nature of the heteroatoms) and the reactivity of the azomethine ylide formed.
2
. Results and discussion
Interaction of 3-alkylsulfanyl-2-arylazoacrylonitriles with N-methyl- and N-phenylmaleimides
The required 3-alkylsulfanylarylazoacrylonitriles 7-9 were synthesized by the S-alkylation of the arylhydrazonothioacetamides 5
11
according to a previously published method in excellent yields (Scheme 2, Table 1). All compounds 7-9 were satisfactorily
1
characterized by H NMR spectroscopy and EI-MS spectrometry (see the Supplementary data for synthetic details and full analytical
and spectroscopic characterization).
Scheme 2. Synthesis of 3-methyl-, 3-allyl- and 3-propargylsulfanyl-2-arylazoacrylonitriles 7-9.
Table 1
The yields of the methyl-, allyl-, propargylsulfanylarylazoacrylonitriles 7a-k, 8a-e and 9a-d
a
Compd,
№
Yield
7-9, (%)
66
Entry
X
Ar
R
1
2
3
4
5
6
7
8
9
7a
8a
9a
7b
8b
9b
7c
8c
9c
7d
8d
9d
7e
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
O
2
2
2
2
2
2
2
2
2
2
2
2
4-NO
4-NO
4-NO
4-ClC
4-ClC
4-ClC
Ph
2
2
2
C
C
C
6
6
6
H
H
H
4
4
4
Me
Allyl
82
Propargyl 91
6
H
4
Me
Allyl
90
91
6
6
H
H
4
4
Propargyl 84
Me
Allyl
83
89
Ph
Ph
Propargyl 72
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
0
4-MeOC
4-MeOC
4-MeOC
4-NO
4-MeOC
3,5-(CF
4-NO
4-ClC
6
6
6
H
H
H
4
4
4
Me
Allyl
82
74
Propargyl 67
2
C
6
H
4
Me
Me
Allyl
Me
Me
Me
Me
Me
64
86
73
70
92
58
85
67
7f
8e
7g
7h
7i
O
O
(CH
(CH
S
6
H
4
3 2 6 3
) C H
C
2
)
)
2
2
6
H
4
2
2
6
H
4
4-NO
4-ClC H
4-CF C H
3 6 4
2 6
C H
6 4
4
7j
7k
S
S
2
a
The isolated yield.
The reaction of 3-alkylsulfanylarylazoacrylonitriles 7a-k, 8a-e and 9a-d with N-methyl- and N-phenylmaleimides 2a,b was
performed at reflux in dry benzene with excess of the dipolarophiles 2 (Scheme 3, Table 2). Compounds 10a-k and 11a-j were
isolated by filtration and further purified by column liquid chromatography. The structures of tricyclic products 10-11 were
1
13
1
13
1
1
confirmed by elemental analysis, EI-MS, and H and C NMR spectra as well as 2D H- C HMQC, HMBC, H- H NOESY
experiments and X-ray data. The molecular ions of compounds 10a-k and 11a-j confirmed the addition of the reagents and the
elimination of methyl-, allyl- or propargylthiol. The IR spectra exhibited absorption bands of the C-H bonds with ν wavenumber at
-
1
-1
-1
1
2
800-3000 cm , the CN-bond ν at 2200 cm and the two carbonyl bonds ν in the region 1700-1720 cm . The H NMR spectra of
cycloadducts 10a-k and 11a-j in DMSO-d contain characteristic signals including: doublets for the H3a proton at δ 5.2-5.5 ppm,
6
doublets of triplets or multiplets at δ 4.2-4.6 ppm for H6 proton, and two doublet of doublets or triplets at δ 3.7-4.1 ppm (J = 9.2-10.0

5
ACCEPTED MANUSCRIPT
and J = 10.0-10.4 Hz) for Н9b. A main feature of the NMR spectra of compounds 10-11 were the downfield shift of the tert-
cycloalkylamine group protons. Registered chemical shift of the protons of this group and their multiplicity confirmed that they have
1
13
participated in the process. It should be mentioned that H and C NMR spectra octahydro-1H-pyrrolo[3,4-a]indolizine 10 and 11a-
d, octahydropyrrolo[3',4':3,4]pyrrolo[1,2-a]azepine 10h,i and 11g,h and hexahydropyrrolo[3',4':3,4]pyrrolo[2,1-c][1,4]thiazine 10j,k
and 11i,j, showed two sets of signals. Such spectral behavior was observed earlier for hexahydropyrrolo[3,4-a]pyrrolizines 3 and 4
(
3
Scheme 1). This fact demonstrates that a mixture of two stereoisomers for compounds 10a-d,h-k and 11a-d,g-j was obtained (Table
). Only the H, C spectra of pyrrolo[3,5-a][1,4]oxazines 10e-g and 11e-f, exhibited the presence of four isomers, although the
1
13
predominance for the one of isomers was also observed.
Scheme 3. 1,3-Dipolar cycloaddition of S,N-acetals 7a-k, 8a-e, and 9a-d vs. hetero-Diels-Alder reaction of the 1,2-diazo-1,3-butadiene system.
Table 2
The time of conversion of the starting materials and yields of cycloadducts 10 for the reactions of 7-9 with N-methyl- and N-phenylmaleimides 2a,b
Entry
Compounds 7-9
Ar
Reaction with 2a (R=Me)
Reaction with 2b (R=Ph)
1
№
X
R
№
Time of
conversion, (h)
2.5
Yield
10a-m, (%)
90
№
Time of
conversion, (h)
4.5
Yield
11a-m, (%)
63
1
7a
CH
2
Me
10a
11a
4
-NO
2
C
6
H
4
2
3
4
8a
9a
7b
CH
CH
CH
2
2
2
4-NO
4-NO
4-ClC H4
2
C
C
6
6
H
H
4
Allyl
Propargyl
Me
10a
10a
10b
1.5
1.0
43
97
70
90
11a
11a
11b
2.0
1.0
12
66
70
90
2
4
6
5
6
7
8
9
1
1
1
1
1
1
1
1
1
2
2
8b
9b
7c
8c
9c
7d
8d
9d
7e
7f
8e
7g
7h
7i
7j
7k
CH
CH
CH
CH
CH
CH
CH
CH
O
O
O
(CH
(CH
S
2
2
2
2
2
2
2
2
4-ClC H4
Allyl
Propargyl
Me
Allyl
Propargyl
Me
Allyl
Propargyl
Me
Me
Allyl
Me
Me
Me
10b
10b
10c
10c
10c
10d
10d
10d
10e
10f
10g
10h
10i
21
21
30
10
6
40
70
20
9
25
20
2.5
-
46
90
-
86
83
70
71
83
91
62
44
61
45
60
98
75
45
50
-
11b
11b
11c
11c
11c
11d
11d
11d
11e
11f
-
8
5
97
81
89
78
84
64
68
58
92
67
-
6
4-ClC H4
6
Ph
Ph
16
11
7
50
50
90
8
20
-
0.5
1.5
40
-
Ph
0
1
2
3
4
5
6
7
9
0
0
4-MeOC
4-MeOC
6
6
H
H
4
4
4-MeOC H4
6
4-NO C H
4
2
6
4-MeOC H4
6
3,5-(CF ) C H
3
3
2
6
2
)
)
2
4-NO C H
2
6
4
11g
11h
11i
-
86
78
67
-
2
2
4-ClC H4
6
4-NO C H
2
6
4
10j
10k
-
S
S
4-ClC H4
Me
Me
6
4-CF C H
4
3
6
11j
45
60
1
1
The stereochemistry of tricyclic compounds 7-8 was assigned in accordance to H- H NOESY experiments. In the case of the Z-
isomer there is a cross-peak for the H-ortho with H6 proton of tricyclic fragment (Scheme 4), while a strong NOESY cross-peak was
1
observed between H-ortho and H3a in E-isomer. Signal of the nodal proton H3a in H NMR spectra Z-isomer compounds 7-8 was
deshielded in comparison to the same signal of E-isomers
.
6
Scheme 4. Selected NMR spectra data for compound 11g (in DMSO-d )

6
ACCEPTED MANUSCRIPT
Table 3
1
The ratio of Z- and E-isomers for compounds 10 and 11a-d in DMSO-d
6
in according the H NMR data
1
Entry
Compound,
R
R = Me
Compound,
R = Ph
№
E-isomer, %
Z-isomer, %
№
E-isomer, %
Z-isomer, %
1
2
3
4
10a
10b
10c
10d
4-NO
4-ClC
Ph
2
C
H
6 4
6
H
4
74
70
65
60
26
30
35
11a
11b
11c
11d
74
-
81
54
26
-
19
36
4-MeOC
6
H
4
40
As can be concluded from the NMR spectral data for products 7-8 (Scheme 4), the E-isomer is the major one in contrast to
4,5
hexahydropyrrolo[3,4-a]pyrrolizines where both stereoisomers are present in equal ratio. All attempts to separate Z- and E-isomers
of compounds 10-11 with column chromatography have failed. This may be explained by the existence of dynamic equilibrium
1
1
between two stereo configurations generated from the nodal H3a proton due to the influence of electron-withdrawing group. The
,6-H shift to the nitrogen atom of the azo group leads to the formation of a tautomer A with a single C4-C4′ bond, then followed by
1
the rotation around this bond (Scheme 5).
Scheme 5 Proposed mechanism of dynamic equilibrium between the E- and Z-isomers compounds 10-11
Single-crystal X-ray determination was performed, confirming the formation of the endo-adduct of the 1,3-dipolar cycloaddition
of the major stereoisomer – namely E-isomer hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]oxazine 10g (Fig. 1).
Fig. 1. Structure of hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]oxazine 10g (X-ray data)
Mechanistic investigation
As discussed above, the 1,2-diaza-1,3-butadiene system did not take part in a [4+2]-cycloaddition reaction with N-methyl- or N-
11
phenylmaleimides 2a,b, instead the [3+2]-cycloaddition occurred (Scheme 6). Previously we have elucidated that this is possibly
due to a 1,6-hydrogen shift that proceeds with relative ease. The nature of this 1,6-shift is a pericyclic reaction assisted by a secondary
12
13
orbital interaction rather than a pseudopericyclic one. This was confirmed by NBO and ACID methods. The spatial distortion of
the π-system framework from planar geometry led to a weaker involvement of the lone pair of electrons located on N1 and a stronger
involvement of the π-electrons. The activation barrier for the respective transition state was higher than the activation energy for the
following cycloaddition. It is well known that relatively high activation barriers in pericyclic reactions are arising from electron-
14
electron repulsion, while in the course of a pseudopericyclic reaction this factor is avoided because of planar geometry and
15
favorable interaction between nucleophilic/electrophilic centers located on the π-system. By varying types of N-cycloalkyl groups in
the 1,2-diaza-1,3-butadiene system, one can achieve a stronger planarity of transition state and thus, the mode of reaction mechanism
can be controlled. Moreover, the change in planarity can also lead to a change in delocalization within the π-system and change the
energies of the frontier orbitals. Thus, indirectly, [4+2]- vs. [3+2]-cycloaddition can be controlled via a change of the character of the
frontier orbitals.

7
ACCEPTED MANUSCRIPT
CN
H
N
CN
H
N
CN
H
N
CN
3
SR1 1,6-H
SR1
SR1
4
SR1
2
1
N
N
Ar
N
Ar
N
Ar
N
N
N
N
Ar
N
5
H
6
A
B
C
7
O
7-9
R
N
O
NC
R1
N
NC
H
N
S
N
N
N
Ar
N
Ar
O
O
N
R1
H
O
O
S
N
R
D
R
1
0-11
Scheme 6. Proposed mechanism of azomethine ylide generation and cycloaddition to N-methyl- and N-phenylmaleimides 2a,b
To address the unresolved question of “structure-mechanism” relationship for this reaction we have performed density
16
11
functionalcalculations at the B3LYP/6-31G** level using Gaussian 09 RevC.01 to connect the geometrical features of S,N-acetals
with their reactivity. In the first step, we have fully optimized substrates 1a,b and 7a,d-g,i,l,m. The true character of the minima for
all structures was confirmed by calculation of the Hessian matrix. Geometric parameters of compounds 1 and 7 were collected in
Table 4.
Table 4
Optimized geometry parameters of compounds 1a,b and 7a,d-g,i,l,m (B3LYP/6-31+G**)
Entry
1
Compounds
№
1a
Optimized geometry parameters
Ar
4-NO
X
CH
rH7-C6, Å
1.096
rN1ꢀꢀꢀH7, Å
2.186
tN1N2C3C4, °
6.2
tN2C3C4N5, °
42.6
tC3C4N5C6, °
16.7
2
C
6
H
4
2
2
3
4
5
6
7
8
9
1b
7a
7d
7e
7f
7g
7l
7i
4-MeOC
4-NO
4-MeOC
4-NO
4-MeOC
4-NO
4-MeOC
4-NO
4-MeOC
6
H
4
CH
(CH
(CH
O
O
(CH
(CH
S
2
1.096
1.086
1.097
1.089
1.095
1.086
1.087
1.089
1.094
2.164
2.473
2.483
2.523
2.448
2.386
2.426
2.577
2.590
-10.1
-3.6
-6.6
-2.5
7.6
-3.5
-1.4
1.1
-36.7
40.4
-34.4
35.6
33.6
42.4
36.7
38.3
33.4
-20.2
31.6
-27.6
30.5
27.3
26.2
30.0
27.0
32.1
2
C
6
H
4
2
)
)
2
6
H
4
2
2
2
C
6
H
4
6
H
4
4
4
2
C
6
H
4
2
)
)
3
6
H
2
3
2 6 4
C H
1
0
7m
6
H
S
1.5
In the second step, the obtained electron density was analyzed by means of the Natural Bond Orbitals (NBO) localization
12
17
scheme and Atoms in Molecules (AIM) analysis. Results of NBO and AIM analyses were listed in Table 5.
Assuming that the transition state (TS) is a superposition of the starting and final states for the process, the TS for a 1,6-H transfer
in compounds 7 is expected to have a non-planar geometry. A non-planar atomic arrangement of the π-system of compounds 7 (see
torsion angles’ values at Table 4) is consistent with the assumption of a pericyclic mechanism. In addition, one can stipulate that the
shorter non-covalent interaction NꢀꢀꢀH should enhance reaction rates. The values of bond lengths, r(HꢀꢀꢀN) and r(CH), depend on the
type of tert-cycloalkylamino fragment and the nature of the substituent in the aromatic ring. As it follows from the results of
calculations (Table 4) the closest NꢀꢀꢀH contact was observed for arylazoacrylonitriles containing pyrrolidine (1a,b), piperidine (7a)
and azepine (7g,h) residues. Thus, a higher probability should be expected for the 1,6-H shift to occur. Indeed, the insertion of an
azepine or piperidine fragment led to the acceleration of the 1,3-cycloaddition reaction. According to experimentally observed values
of time vs. conversion (Table 2), the cycloaddition goes at a faster rate (2.5-4.5 h) for compounds 7a against 8-9 h for compounds 7e
or 40-46 h for compounds 7i. To estimate the nature and the strength of the NꢀꢀꢀH interaction we have performed NBO and AIM
analysis to obtain the electron density. According to the NBO data presented in the Table 5, a very weak bonding was registered
between N1 and H7, as a result of the overlapping of the π(N1-N2) or/and LP(N1) orbitals with the σ*(C6-H7) orbital. This
interaction was observed for the compounds 1a,b,7f. Interestingly, these alkylsulfanylarylazoacrylonitriles exhibited higher rates of
conversion (Table 5). The stabilization energy values for this interaction were between 0.6 and 2.8 kcal/mol.
The value of electron density ρ(BCPNꢀꢀꢀH) at the bond critical points, BCP (3,-1), can provide information about the strength of
this interaction. Topological AIM analysis of electron density for compounds 7 supported the existence of an interaction between N1
and H7 atoms in all compounds (except S,N-acetals 7e,j,n), since NꢀꢀꢀH bond critical point was located. According to hydrogen bond
-3
18
classification by AIM descriptors, the value of electron density, ρ(BCPNH), which was calculated to be in range between 2.000•10
-
2
a.u. and 3.500•10 a.u. (Table 5), suggests that the NꢀꢀꢀH hydrogen bond is moderately strong.
The degree of electron density expansion from the lone pair of electrons on the N1 atom to the vacant σ*(C6-H7) bond may be
quantitatively characterized by the covalence ratio factor (χ) for the formed NꢀꢀꢀH bond via equation (eq. 1), as previously introduced
19
by F. Weinhold and coworkers.

8
ACCEPTED MANUSCRIPT
ꢁ
ꢂ ꢄꢂ ꢆꢇꢈ
ꢃ ꢅ ꢃꢅ
ꢀ
= ꢁ
ꢊ≤ ꢋꢊꢊꢊꢊꢊ
(1)
ꢂ ꢄꢂ ꢆꢇꢁꢉ ꢄꢉ ꢆ
ꢃ
ꢅ
ꢃ
ꢅ
where R and R stand for the van der Waals radii and r и r for the covalent radii of the interacting atoms; d is experimentally
N
H
N
H
NH
determined (or calculated) contact.
Table 5
The data of the electron density analysis between C-H and NꢀꢀꢀH atoms during 1,6-H shift by the NBO and AIM (B3LYP/6-31+G**) methods and the X-ray
data
Entry
1
Compd., N
NBO (B3LYP/6-31+G**)
E(2)n → σ*, kcal/mol
2.64
AIM (B3LYP/6-31+G**)
E(2) π → σ*, kcal/mol
0.65
ρ(BCPNꢀꢀꢀH),
ρ (BCPC-H),
Covalence
ratio factor, χ
0.31
-2
-1
ɬ10 a.u.
ɬ10 a.u.
1a
2.1198
2.8524
2
3
4
1b
7a
7d
2.80
-
-
0.65
0.74
-
2.1928
1.2352
1.3733
2.8506
2.9162
2.8268
0.32
0.14
0.13
5
6
7
8
9
7e
7f
7g
7m
7j
-
-
-
-
2.7826
2.7741
2.8533
2.9143
2.8223
2.7882
0.13
0.15
0.19
0.16
0.07
0.07
0.58
1.4882
1.4846
1.3822
-
-
-
-
-
-
0.69
0.53
-
-
1
0
7n
The covalence ratio for these compounds were ~7-32% and this was decreasing in the series:
b > 1a > 7g > 7 m > 7f > 7a > 7d ≈ 7e > 7j ≈ 7n
The canonical orbital diagram (Fig. 2) constructed with the help of B3LYP/6-31G** level using the Gaussian 09 RevC.0116
1
method suggests that the cycloaddition reaction is driven by the interaction between the HOMO of the dipole (S,N-acetal 7g) and the
LUMO located on the dipolarophile 2a.
-
2.80 eV
5.57 eV
-
3.03 eV
E=2.54 eV
E=3.05 eV
-3.09 eV
∆
∆
-
-6.08 eV
-
8.74 eV
Fig. 2. Orbital diagram for the two directions of the S,N–acetals 7g reaction with N-methylmaleimides 2a
We suggested that the cycloaddition could proceed through two following reaction pathways:
a) The first one includes reaction of dienophile 2a with S,N-acetal 7 as the diene. This mechanism i.e. [4+2]-cycloaddition is
shown on the left side of the Fig. 2.
b) The second one starts with a 1,6-shift yielding dipole A. Then, the newly generated dipole reacts with dipolarophile 2a. This
process is depicted on the right half of the Fig. 2.
(
(

9
ACCEPTED MANUSCRIPT
A comparison of the energy gap between the frontier orbitals for both pathways favors the [3+2]-cycloaddition. Its gap ∆E was
calculated to be 2.54 kcal/mole, while for [4+2]-cycloaddition (pathway a) the energy gap was 3.05 kcal/mol.
According to NBO calculations the HOMO of dipole for 7g can be represented as a following combination of NBOs:
HOMO
LP(C7)
π(C4N6)
π*( C4N6)
π (N2C3)
LP (S5)
LP (N1)
π*(N2C3)
Ψ
(Dipole A) = 0.481 χ
+ 0.387χ
- 0.383 χ
+ 0.327χ
- 0.281χ
+0.241χ
+ 0.239χ
(2)
Higher coefficients for NBOs localized on C7, N6 and C4 atoms are in line with the involvement of the 1,3-dipole in
cycloaddition rather than the involvement of the diazadiene system.
Conclusion
In this paper, we describe the reactivity of azomethine ylides generated from alkylsulphanylarylazoacrylonitriles 7-9 toward
substituted maleimides 2a,b, which led to a [3+2]-cycloaddition reaction independent of the type of tert-cycloalkylaminogroup,
substituents at the aromatic ring and thio fragment. A variety of N- cycloalkyl groups, such as piperidine, morpholine, thiomorpholine
and azepine, may be introduced in structure of alkylsulfanylarylazoacrylonitriles without change in the reaction outcome. Thus we
have extended the scope of this new method for the generation of azomethine ylides from available diazadienes with terminal S,N-
acetal group.
A quantum chemistry study has shown that simultaneous 1,6-H shift occurs to generate reactive ylide species and this mechanism
distinguishes this method considerably from other well-known routes. Extended conjugation of the 1,2-diaza-1,3-butadiene π-system
linked with aromatic and tert-cycloalkylamino groups in the terminal positions is a key features in this approach.
Ylides lacking stabilizing groups in cycloalkylamine fragment underwent cycloaddition with N-methyl- and N-phenylmaleimides
resulting in non-aromatic heterocyclic endo-adducts with high yields. The observed high stereoselectivity of the reaction occurring in
mild conditions has allowed us to develop a facile synthesis of functionalized - dioxohexahydro-1H-pyrrolo[3,4-a]indolizine,
hexahydropyrrolo[3',4':3,4]pyrrolo[2,1-c][1,4]oxazine,
hexahydropyrrolo[3',4':3,4]pyrrolo[2,1-c][1,4]thiazine
and
octahydropyrrolo[3',4':3,4]pyrrolo[1,2-a]azepine. This protocol can be incorporated in new routes toward piperidine, or indolizidine
natural alkaloids and their analogs, since these heterocycles are the main cyclic fragments in their structure.
Experimental section
4
.1. General
Melting points were determined with a Stuart SMP3 apparatus. Н NMR and C NMR spectra were recorded on a Bruker Avance
1
13
1
13
II (400 MHz for H and 100.6 MHz for C) spectrometer using DMSO-d and CDCl as solvents. Chemical shifts (δ) have been
reported in parts per million (ppm) relative to TMS in H and C spectra. Coupling constants (J) values given in Hertz. Mass spectra
6
3
1
13
were performed on a «SHIMADZU GCMS-QP2010 Ultra» mass spectrometer using the electron impact ionization technique (40-
o
2
00 C, 70 eV). The IR data have been recorded on a Bruker Alpha (NPVO, ZnSe) IR-Fur spectrometer. Elemental analyses were
carried out using a CHNS/O analyzer Perkin-Elmer 2400 Series II instrument. Single crystal X-ray diffraction analyses have been
performed on an Xcalibur S CCD area-detector diffractometer (MoKα irradiation, ω-scanning with step 1o, 295(2) K). Absorption
2
0
correction was not performed. Solution and refinement of structures were accomplished with the SHELXTL program package.
o
For 10g, the crystal system is triclinic, a = 8.289(2) Å, b = 8.6627(12) Å, c = 13.0570(14) Å, α = 94.191(12) , β = 93.649(16)o, γ
99.640(16) , space group P-1, Volume 919.1(3) Å3, Z = 2, ꢁ = 0.216 mm . Reflections collected/independent/with [I >
σ(I)].038/5775/2453, R = 0.0315, completeness to θ = 26.00 98.5 %. S = 1.001, final R indices: R = 0.0487, wR = 0.0806 [I >
int
1 2
o
-1
=
2
2
o
1
2
σ(I)], R = 0.1296, wR = 0.0888 (all data). Largest diff. peak and hole: 0.461 and –0.419 ēÅ-3.
CCDC 902766 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via link www.ccdc.cam.ac.uk/data_request/cif.
Chromatographic purification of compounds 10-11 was done using silica gel (0.035–0.070, 60 Å). The reactions were monitored
on silica gel plates (Sorbfil UV–254) and visualization was effected by short wavelength UV light (254 nm). Solvents were dried and
distilled according to the common procedure.
16
All calculations have been done with a help of G09 2 suit. Structures were initially optimized at the B3LYP/6-31G* level of
theory. All located points had a minima character according to Hessian calculation. NBO analysis was performed at the same level of
21
theory by using the appropriate module, implemented in G09. The obtained B3LYP/6-31G* wave functions were studied by the
22
AIM method with the help of AIMAll software.
1
1,23
Arylhydrazonoethanethioamides 5 and S,N-acetals 7-9 were prepared by the procedure reported in our previous articles.
.2. Reaction S,N-acetals 7-9 with N-methyl- and N-phenylmaleimides 2a,b.
4
General procedure: A solution of 0.3 mmol of S,N-acetals 7-9 and 1.5 mmol dipolarophiles 2a,b was heated at reflux in 10 ml of
benzene (TLC). Products were filtered and purified by liquid column chromatography (eluent: chloroform-acetone 20:1)
4
(
.2.1.
10а). From 7a and 2a (0.105 g, 90%), 8a and 2a (0.114 g, 97%), 9a and 2a (0.083 g, 70%) as an orange solid, m.p. 269-270 C;
Mixture of isomers (1:3); [Found: C, 57.8; H, 4.47; N, 21.5. C H N O requires C, 57.86; H, 4.60; N, 21.3%]; ν 3100, 3030,
2-(2-Methyl-1,3-dioxo-6,7,8,9,9a,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizin-4-ylidene)-2-[(4-nitrophenyl)azo]acetonitrile
o
19
18
6
4
max
-
1
2
950, 2860, 2200, 1720 cm ; δ (400 MHz, DMSO-d ) 8.28 and 7.84, 8.28 and 7.65 (4H, two AA'XX', J 8.6 Hz, Ar), 5.22 and 4.72
H
6
(1H, two d, J 9.2 Hz, CH), 5.22 and 4.83 (1H, two d, J 12.2 Hz, CH), 4.29 (1Н, dt, J 10.2, 2.6 Hz, CH), 3.83 and 3.78 (1H, t, J 9.7
Hz, CH), 3.41-3.33 (m, 1H, CH), 2.89 (3H, s, NMe), 2.09-1.95 (1H, m, CH), 1.90-1.76 (2H, m, CH ), 1.63-1.49 (2H, m, CH ), 1.35-
2
2
1
.19 (1H, m, CH); δ (100.6 MHz, DMSO-d ) 174.5 (CO), 172.6 (CO), 160.5 (C), 146.2 (C), 125.2 (CH), 122.4 (CH), 117.1 (C),
c 6

1
0
ACCEPTED MANUSCRIPT
14.4 (C), 100.1 (C), 67.2 (CH), 53.8 (CH), 47.0 (CH ), 42.9 (CH), 29.1 (CH ), 25.6 (NCH ), 24.4 (CH ), 23.2 (CH ); m/z (I, %): 394
2 2 3 2 2
+
1
(25, М ).
4
.2.2. 2-[(4-Chlorophenyl)azo]-2-(2-methyl-1,3-dioxo-6,7,8,9,9a,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizin-4-
ylidene)acetonitrile (10b). From 7b and 2a (0.103 g, 90%), 8b and 2a (0.100 g, 86%), from 9b and 2a (0.98 g, 83%) as a yellow
o
solid, m.p. 273-274 C; Mixture of isomers (1:2); [Found: C, 59.5; H, 4.5; N, 18.1. C H ClN O requires C, 59.45; H, 4.73; N,
19
18
5
2
-
1
1
8.25%]; νmax 1710, 2190, 2860, 2920, 2955 cm ; δ (400 MHz, DMSO-d ) 7.68 and 7.49, (4H, AA'XX', J 8.8 Hz, Ar), 5.21 and 4.75
H
6
(1H, two d, J 9.2 Hz, CH) 5.20 and 4.64 (1H, d, J 11.9 Hz, CH), 4.21 (1Н, dt, J 10.0, 3.2 Hz, СН), 3.82 and 3.78 (1H, two dd, J 9.2,
1
0.4 Hz, CH ), 3.42-3.34 (1H, m, CH ), 2.89 and 2.87 (3H, two s, NMe), 2.07-1.94 (1H, m, CH ), 1.90-1.72 (2H, m, CH ), 1.59-1.45
2
2
2
2
(
2H, m, CH ), 1.27-1.12 (1H, m, CH ); δ (100.6 MHz, DMSO-d ) 174.8 (CO), 173.1 and 172.9 (C), 160.9 and 155.6 (C), 152.1 and
2 2 c 6
1
6
51.7 (C), 132.9 and 132.4 (C), 129.8 and 129.4 (CH), 123.6 and 123.2 (CH), 115.9 and 115.0 (C), 104.3 and 101.4 (C), 66.8 and
6.3 (CH), 53.9 and 52.9 (CH), 49.3 and 46.5 (CH ), 43.9 and 43.0 (CH), 29.2 and 29.0 (CH ), 25.7 and 25.6 (NCH ), 24.6 and 24.2
2
2
3
+
(CH ), 23.3 and 23.2 (CH ); m/z (I, %): 383 (20, М ).
2
2
4
(
.2.3. 2-(2-Methyl-1,3-dioxo-6,7,8,9,9a,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizin-4-ylidene)-2-(phenylazo)acetonitrile
10c). From 7c and 2a (74 g, 70%), from 8c and 2a (75 g, 71%), from 9c and 2a (87 g, 83%) as a yellow solid, m.p. 286-287 C;
Mixture of two isomers (4:7); [Found: C, 65.2; H, 5.4; N, 20.1. C H N O requires C, 65.32; H, 5.48; N, 20.04%]; ν 1710, 2200,
o
19
19
5
2
max
-
1
2
860, 2920, 2960, 3000, 3030, 3060 cm ; δ (400 MHz, DMSO-d ) 7.68 (1H, d, J 7.2 Hz, Ar), 7.55-7.18 (4H, m, Ar), 5.25 and 4.77
H
6
(1H, two d, J 12.6 Hz, CH), 5.20 and 4.63 (1H, two d, J 9.0 Hz, CH), 4.18 (1Н, dt, J 12.6, 9.0 Hz, СН), 3.82 and 3.76 (1H, two t, J
1
0.2 Hz, CH ), 3.43-3.18 (1H, m, CH ), 2.92 and 2.90 (3H, two s, NMe), 2.16-1.98 (1H, m, CH ), 1.97-1.70 (2H, m, CH ), 1.67-1.38
2
2
2
2
(
2H, m, CH ), 1.26-1.03 (1H, m, CH ); δ (100.6 MHz, DMSO-d ) 173.6 (CO), 171.9 and 171.6 (CO), 160.0 and 154.6 (C), 152.8
2 2 c 6
and 152.5 (C), 132.2 and 132.0 (C), 129.3 and 129.0 (CH), 128.9 and 128.8 (CH), 121.4 and 121.1 (C), 115.6 and 114.8 (C), 103.7
and 101.0 (C), 66.5 and 65.9 (CH), 53.69 and 52.6 (CH), 48.7 and 46.0 (CH ), 43.7 and 42.7 (CH), 28.9 and 28.6 (CH ), 24.1 and
2
2
+
2
3.7 (CH ), 23.0 and 22.8 (CH ); m/z (I, %): 349 (25, М ).
2
2
4
.2.4. 2-[(4-Methoxyphenyl)azo]-2-(2-methyl-1,3-dioxo-6,7,8,9,9a,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizin-4-
ylidene)acetonitrile (10d). From 7d and 2a (0.103 g, 91%), from 8d and 2a (0.070 g, 62%), from 9d and 2a (0.50 g, 44%) as a yellow
o
solid, m.p. 223-224 C; Mixture of isomers (2:3); [Found: C, 63.2; H, 5.7; N, 18.4. C H N O requires C, 63.31; H, 5.58; N,
20
21
5
3
-
1
1
5
8.46%]; νmax 1710, 2190, 2850, 2920, 2960, 3070 cm ; δ (400 MHz, DMSO-d ) 7.65, 7.49, 6.96, (4H, two AA'XX', J 9.0 Hz, Ar),
.24 and 4.77 (1H, two d, J 11.6 Hz, CH), 5.14 and 4.57 (1H, two d, J 9.0 Hz, CH), 4.11 (1Н, dt, J 11.6, 2.4 Hz, CH), 3.83 (3Н, s,
H
6
OMe), 3.80-3.72 (m, 1H, CH ), 3.30-3.20 (1H, m, CH ), 2.93 and 2.92 (3H, two s, NMe), 2.06 (1H, t, J 12.2 Hz, CH ), 2.00-1.89 (1H,
2
2
2
m, CH ), 1.85-1.80 (1H, m, CH ), 1.65-1.50 (2H, m, CH ), 1.35-1.10 (1H, m, CH ); δ (100.6 MHz, DMSO-d ) 175.0 (CO), 173.5
2
2
2
2
c
6
and 173.2 (CO), 160.2 and 154.2 (C), 159.8 and 159.7 (C), 147.5 and 147.1 (C), 123.5 and 123.2 (CH), 116.3 and 115.4 (C), 115.0
and 114.6 (C), 103.9 and 101.0 (C), 66.2 and 65.7 (CH), 55.9 and 55.8 (OCH ), 53.6 and 52.6 (CH), 49.1 and 46.3 (CH ), 44.0 and
3
2
+
4
3.0 (CH), 29.3 and 29.0 (CH ), 25.6 and 25.2 (NCH ), 24.6 and 24.3 (CH ), 23.4 and 23.2 (CH ); m/z (I, %): 379 (46, М ).
2 3 2 2
4
.2.5. 2-(8-Methyl-7,9-dioxo-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]oxazin-6-ylidene)-2-[(4-
o
nitrophenyl)azo]acetonitrile (10e). From 7e and 2a (0.072 g, 61%) as an orange solid, m.p. 326-327 C; Mixture of isomers
2:12:1:6); [Found: C, 54.7; H, 4.1; N, 21.3. C H N O requires C, 54.55; H, 4.07; N, 21.20%]; ν 1710, 2200, 2855, 2950, 3090
(
18
16
6
5
max
-
1
cm ; δ (400 MHz, DMSO-d ) 8.30, 7.89, 7.83, 7.69 (4H, four AA'XX', J 9.2 Hz, Ar), 5.31, 5.19, 5.07, 4.98 (1H, four d, J 9.2 Hz,
H
6
CH), 4.77, 4.68, 4.65, 4.59 (1H, four d, J 8.8 Hz, CH), 4.36 (1Н, dt, J 10.8, 3.6 Hz, СН), 4.11 (1Н, dt, J 12.0, 3.6 Hz, СН), 4.02-3.80
(
2H, m, CH ), 3.71-3.53 (2Н, m, CH ), 3.39-3.28 (1H, m, CH ), 2.88 and 2.86 (3H, two s, Me); δ (100.6 MHz, DMSO-d ) 175.4 and
2 2 2 c 6
1
1
6
75.3 and 174.1 (CO), 173.7 and 172.6 and 172.3 (CO), 162.7 and 162.2 (C), 158.0 and 157.4 and 157.0 (C), 146.5 and 146.4 (C),
25.4 and 125.2 (CH), 122.7 and 122.5 and 122.3 (CH), 115.3 and 115.0 and 114.4 (C), 106.1 and 103.3 and 102.7 and 100.0 (C),
8.4 and 68.3 (CH ), 64.8 and 64.3 (CH ), 64.1 and 67.7 (CH), 54.0 and 53.2 (CH), 46.9 and 46.8 (CH ), 41.9 and 41.1.6 (CH), 25.9
2
2
2
+
and 25.8 and 25.7 (NCH ); m/z (I, %): 396 (39, М ).
3
4
.2.6. 2-[(4-Methoxyphenyl)azo]-2-(8-methyl-7,9-dioxo-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]oxazin-6-
o
ylidene)acetonitrile (10f). From 7f and 2a (0.051 g, 45%) as a yellow solid, m.p. 280-281 C; Mixture of isomers (1:1); [Found: C,
6
-
1
0.0; H, 4.9; N, 18.4. C H N O requires C, 59.84; H, 5.02; N, 18.36%]; ν 1700, 2195, 2830, 2965, 2995 cm ; δ (400 MHz,
19 19 5 4 max H
DMSO-d ) 7.70, 7.54, 7.03, 7.00 (4H, two AA'XX', J 9.2 Hz, Ar), 5.11 and 4.56 (1H, two d, J 8.9 Hz, CH), 4.88 and 4.46 (1H, two d,
6
J 12.3 Hz, CH), 4.22 (1Н, dt, J 12.3, 3.6 Hz, СН), 4.09 (1Н, dt, J 12.0, 3.2 Hz, СН), 3.91 (3Н, s, ОМе), 3.93-3.75 (2H, m, CH2),
3
1
6
.63-3.45 (2H, m, CH ), 2.87 and 2.73 (4H, m, NMe+CH); δ (100.6 MHz, DMSO-d ) 174.7 (CO), 173.4 and 172.8 (CO), 160.4 and
2
c
6
60.1 (C), 159.7 and 155.1 (C), 147.7 and 147.3 (C), 128.8 and 123.6 (CH), 115.1 and 115.0 (C), 114.9 and 114.6 (CH), 102.7 (C),
4.8 and 64.9 (CH ), 62.5 and 62.4 (CH ), 59.8 and 59.7 (CH), 55.9 and 55.6 (NMe), 52.6 and 55.3 (CH), 49.4 and 45.6 (CH ), 4.3
2
2
2
+
and 40.7 (CH), 25.8 (OMe); m/z (I, %): 381 (29, М ).
4
.2.7. 2-[3,5-Bis(trifluoromethyl)phenyl]azo-2-(8-methyl-7,9-dioxo-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-
o
a][1,4]oxazin-6-ylidene)acetonitrile (10g). From 8e and 2a (0.09 g, 60%) as a yellow solid, m.p. 225-226 C; Mixture of isomers
(
12:3:2:2); [Found: C, 49.1; H, 2.9; N, 14.4. C H F N O requires C, 49.29; H, 3.10; N, 14.37%]; δ (400 MHz, DMSO-d ) δ 8.29,
20 15 6 5 3 H 6
8
4
3
.21, 8.16, 7.97, 7.95, 7.88, 7.82, 7.78, 7.53 (3Н, all s, Ar), 5.23, 5.11, 5.05 and 4.95 (1H, four d, J 9.6 Hz, CH), 4.75, 4.71, 4.68 and
.63 (1H, four d, J 8.8 Hz, CH), 4.33 (1H, dt, J 10.8, 3.2 Hz, CH), 4.14 (1Н, dd, J 11.6, 3.2 Hz, СН ), 3.96-3.83 (2Н, m, СН ), 3.70-
2
2
+
.53 (2Н, m, СН ), 3.34 (1Н, t, J 11.6 Hz, СН ), 2.92 and 2.91 (3Н, two s, Me); m/z (I, %): 487 (40, М ).
2
2
4
.2.8. 2-(2-Methyl-1,3-dioxo-3a,6,7,8,9,10,10a,10b-octahydropyrrolo[1,2]pyrrolo[3,5-a]azepin-4-ylidene)-2-[(4-
o
nitrophenyl)azo]acetonitrile (10h). From 7g and 2a (0.120 g, 98%) as an orange solid, m.p. 205-206 C; Mixture of isomers (3:7);
-
1
[
Found: C, 58.7; H, 4.9; N, 20.39. C H N O requires C, 58.82; H, 4.94; N, 20.58%]; ν 1720, 2195, 2850, 2925 cm ; δ (400
20 20 6 4 max H

1
1
ACCEPTED MANUSCRIPT
MHz, DMSO-d ) 8.28, 7.83, 7.65 (8.28, 7.83, 8.28 and 7.65 (4H, two AA'XX', J 9.2 Hz, Ar), 5.33 and 4.82 (1H, two d, J 9.2 Hz,
6
CH), 4.77-4.62 (1H, m, CH), 4.46 and 4.33 (1Н, two dt, J 5.2, 15.2 Hz, CH), 3.76-3.61 (1Н, m, CH), 3.45-3.32 (1Н, m, CH), 2.88
(
3H, s, NMe), 2.10-1.97 (1H, m, CН), 1.93-1.73 (3H, m, CН ), 1.70-1.49 (3H, m, CH ), 1.35-1.23 (1H, m, CH); δ (100.6 MHz,
2
2
c
DMSO-d ) 175.1 (CO), 172.3 (CO), 163.2 (C), 157.9 and 157.5 (C), 146.0 (C), 123.5 and 123.2 (CH), 116.3 and 115.4 (C), 115.0 and
6
1
14.6 (C), 103.9 and 101.0 (C), 66.2 and 65.7 (CH), 55.9 and 55.8 (OCH ), 53.6 and 52.6 (CH), 49.1 and 46.3 (CH ), 44.0 and 43.0
3 2
+
(CH), 29.3 and 29.0 (CH ), 25.6 and 25.2 (NMe), 24.6 and 24.3 (CH ), 23.4 and 23.2 (CH ); m/z (I, %): 408 (11, М ).
2
2
2
4
.2.9. 2-[(4-Chlorophenyl)azo]-2-(2-methyl-1,3-dioxo-3a,6,7,8,9,10,10a,10b-octahydropyrrolo[1,2]pyrrolo[3,5-a]azepin-4-
o
ylidene)acetonitrile (10i). From 7h and 2a (0.09 g, 75%) as a yellow solid, m.p. 250-251 C; Mixture of isomers (2:3); [Found: C,
6
-
1
0.5; H, 4.8; N, 17.3. C H ClN O requires C, 60.38; H, 5.07; N, 17.60%]; ν 1700, 2200, 2860, 2920, 2955, 3050, 3080 cm ; δ
20 20 5 2 max H
(
400 MHz, DMSO-d ) 7.65, 7.37, 7.48 and 7.38 (4H, two AA'XX', J 8.8 Hz, Ar), 5.24 and 4.74 (1H, two d, J 9.2 Hz, CH), 4.63-4.53
6
(
1H, m, CH), 4.51 and 4.35 (1Н, two dt, J 5.2, 14.8 Hz, СН), 3.85 and 3.79 (1Н, two t, J 10.0 Hz, CH ), 3.63-3.49 (1Н, m, CH ), 2.91
2
2
and 2.90 (3H, two s, Me), 2.08-1.95 (1Н, m, CH ), 1.94-1.76 (3H, m, CH ), 1.71-1.52 (3H, m, CH ), 1.37-1.19 (1H, m, CH ); δ
2
2
2
2
C
(
100.6 MHz, DMSO-d ) 175.3 (CO), 172.8 and 172.6 (CO), 161.8 and 156.2 (C), 152.1 and 151.9 (C), 132.6 and 132.4 (C), 129.8
6
and 129.4 (CH), 123.6 and 123.2 (CH), 116.0 and 115.1 (C), 104.3 and 101.2 (C), 69.8 and 69.0 (CH), 54.5 and 53.5 (CH), 50.3 and
7.9 (CH ), 44.1 and 43.4 (CH), 30.4 and 30.3 (CH ), 28.0 and 27.8 (CH ), 27.1 and 26.4 (CH ), 25.6 and 25.5 (NCH ), 24.0 and 23.6
4
2
2
2
2
3
+
(CH ); m/z (I, %): 397 (15, М ).
2
4
.2.10. 2-(8-Methyl-7,9-dioxo-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]thiazin-6-ylidene)-2-[(4-
o
nitrophenyl)azo]acetonitrile (10j). From 7i and 2a (0.055 g, 45%) as an orange solid, m.p. 278-279 C; Mixture of isomers (1:3);
-
1
[
Found: C, 52.7; H, 3.6; N, 20.2. C H N O S requires C, 52.42; H, 3.91; N, 20.38%]; ν 1705, 2195, 2920, 2960 cm ; δ (400
18 16 6 4 max H
MHz, DMSO-d ) 8.26, 7.86, 8.25 and 7.67 (4H, two АА'ХХ', J 8.8 Hz, Ar), 5.60 and 5.19 (1Н, two dt, J 13.2, 2.8 Hz, СН), 5.22 and
6
4
2
.73 (1H, two d, J 9.2 Hz, CH), 4.51-4.41 (1Н, m, СН), 3.96 and 3.90 (1Н, two t, J 10.0 Hz, СН ), 3.58 (1Н, t, J 11.6 Hz, СН ), 3.03-
2
2
.95 (1H, m, CH ), 2.92 and 2.91 (3Н, two s, Ме), 2.84-2.72 (2H, m, CH ), 2.71-2.64 (1H, m, CH ); δ (100.6 MHz, DMSO-d ) 174.2
2
2
2
c
6
(CO), 172.3 (CO), 163.2 (C), 157.4 (C), 146.3 (C), 125.5 and 125.2 (CH), 122.6 and 122.4 (CH), 115.3 and 114.6 (C), 103.1 (C),
6
2
7.9 and 67.6 (CH), 53.7 and 52.7 (CH), 52.6 and 49.6 (CH ), 44.4 and 43.5 (CH), 29.5 (CH ), 25.8 (NCH ), 25.7 and 25.6 (CH ),
2
2
3
2
+
3.3 and 23.2 (CH ); m/z (I, %): 412 (30, М ).
2
4
.2.11. 2-[(4-Chlorophenyl)azo]-2-(8-methyl-7,9-dioxo-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]thiazin-6-
o
ylidene)acetonitrile (10k). From 7j and 2a (0.060g, 50%) as a yellow solid, m.p. 240-241 C; Mixture of isomers (3:5); [Found: C,
3.7; H, 4.1; N, 17.3. C H ClN O S requires C, 53.80; H, 4.01; N, 17.43%]; δ (400 MHz, DMSO-d ) 7.51, 7.40, 7.68 and 7.38
5
18
16
5
2
H
6
(4H, two АА'ХХ', J 8.4 Hz, Ar), 5.59 and 5.15 (1Н, two br. d, J 13.6 Hz, СН), 5.17 and 4.65 (1H, two d, J 9.2 Hz, CH), 4.38 (1Н, dt,
J 11.2, 3.2 Hz, СН ), 3.93 and 3.86 (1Н, two t, J 10.0 Hz, СН ), 3.63-3.48 (1H, m, CH ), 2.93 and 2.91 (3Н, two s, NMe), 2.98-2.87
2
2
2
(
1H, m, CH ), 2.84-2.61 (3H, m, CH );. δ (100 MHz DMSO-d ) 174.4 and 174.3 (CO), 172.7 and 172.5 (CO), 161.9 and 156.2 (C),
2 2 C 6
1
6
2
52.6 and 151.6 (C), 133.2 and 132.7 (C), 129.4 and 128.8 (CH), 123.7 and 123.4 (CH), 115.7 and 115.0 (C), 104.6 and 101.9 (C),
7.2 and 66.8 (CH), 53.2 and 52.2 (C), 51.9 and 49.2 (CH ), 44.5 and 43.6 (CH), 29.8 and 28.5 (CH ), 26.2 and 25.7 (CH ), 25.8 and
5.7 (NMe); m/z (I, %): 401 (34, М ).
2
2
2
+
4
.2.12. 2-(1,3-Dioxo-2-phenyl-6,7,8,9,9a,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizin-4-ylidene)-2-[(4-nitrophenyl)azo] acetonitrile
(
2
2
11a). From 7a and 2b (0.086 g, 63%), from 8a and 2b (0.090 g, 66%), from 9a and 2b (0.095 g, 70%) as an orange solid, m.p. 259-
o
60 C; Mixture of isomers (1:3); [Found: C, 63.1; H, 4.4; N, 18.4. C H N O requires C, 63.15; H, 4.42; N, 18.41%]; ν 1720,
24 20 6 4 max
-1
200, 2860, 2920, 2950, 3070 cm ; δ (400 MHz, DMSO-d ) 8.24, 7.81, 8.24 and 7.66 (4H, two AA'XX', J 9.1 Hz, Ar), 7.59-7.38
H
6
(3Н, m, Ar), 7.37-7.25 (2Н, m, Ar), 5.42 and 4.90 (1H, two d, J 9.2 Hz, CH), 5.30 and 4.88 (1H, two d, J 12.8 Hz, CH), 4.36 (1Н, dt,
J 12.2, 3.2 Hz, СН), 4.03 and 3.98 (1H, two t, J 10.0 Hz, CH ), 3.53-3.34 (1H, m, CH ), 2.22-2.09 (1H, m, CH ), 2.05-1.82 (2H, m,
2
2
2
CH ), 1.81-1.56 (2H, m, CH ), 1.54-1.10 (1H, m, CH ); δ (100.6 MHz, DMSO-d ) 173.9 (CO), 171.9 and 171.7 (CO), 162.0 (С),
2
2
2
C
6
1
1
57.6 (C), 154.5 (С), 146.3 and 146.1 (C), 132.7 and 132.5 (C), 129.5 and 129.4 (CH), 129.3 and 129.2 (CH), 127.9 and 127.7 (CH),
25.6 and 125.2 (CH), 122.4 and 122.2 (CH), 116.6 and 114.7 (C), 102.8 and 91.1 (C), 68.0 and 67.4 (CH), 53.7 (CH), 47.8 and 47.1
+
(CH ), 44.1 and 43.1 (CH), 29.1 (CH ), 24.2 and 23.38 and 23.4 (CH ); m/z (I, %): 456 (19, М ).
2
2
2
4
.2.13. 2-[(4-Chlorophenyl)azo]-2-(1,3-dioxo-2-phenyl-6,7,8,9,9a,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizin-4-
ylidene)acetonitrile (11b). From 7b and 2b (0.120 g, 90%), 8b and 2b (0.129 g, 97%), 9a and 2b (0.108 g, 81%) as an orange solid,
o
m.p. 279-280 C; Mixture of isomers (3:7); [Found: C, 64.6; H, 4.7; N, 15.7. C H ClN O requires C, 64.65; H, 4.52; N, 15.71%];
24
20
5
2
-
1
νmax 1700, 2200, 2850, 2920, 2950 cm ; δ (400 MHz, DMSO-d ) 7.64 (1Н, d, J 8.7 Hz, Ar), 7.58-7.23 (8H, m, Ar), 5.34 and 4.87
H
6
(1H, two d, J 9.2 Hz, CH), 5.29 and 4.80 (1H, two d, J 10.6 Hz, CH), 4.26 (1Н, dt, J 11.5, 3.2 Hz, СН), 4.07 and 3.94 (1H, dd, J 9.6,
9
.2 Hz, CH ), 3.50-3.29 (1H, m, CH ), 2.22-2.06 (1H, m, CH ), 2.01-1.78 (2H, m, CH ), 1.75-1.33 (2H, m, CH ), 1.27-1.02 (1H, m,
2
2
2
2
2
CH ); δ (100.6 MHz, DMSO-d ) 173.5 (CO), 171.7 and 171.5 (CO), 160.2 and 154.9 (C), 151.6 and 151.2 (C), 132.4 and 132.2 (C),
2
C
6
1
32.0 and 131.9 (C), 129.3 and 129.0 (CH), 128.9 (CH), 128.8 and 128.7 (CH), 127.3 and 127.2 (CH), 123.0 and 122.7 (CH), 115.4
and 114.6 (C), 103.7 and 101.0 (CN), 66.7 and 66.1 (CH), 53.8 and 52.7 (CH), 48.8 and 46.1 (CH ), 43.6 and 42.7 (CH), 28.9 and
2
+
2
8.6 (CH ), 24.1 and 23.7 (CH ), 22.9 and 22.8 (CH ); m/z (I, %): 445 (34, М ).
2 2 2
4
.2.14. 2-(1,3-Dioxo-2-phenyl-6,7,8,9,9a,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizin-4-ylidene)-2-(phenylazo)acetonitrile
(11c).
o
From 7c and 2b (0.110 g, 89%), 8c and 2b (0.096 g, 78%), 9c and 2b (0.103 g, 84%) as a yellow solid, m.p. 227-228 C; Mixture of
isomers (2:3); [Found: C, 69.9; H, 5.1; N, 16.8%. C H N O requires C, 70.1; H, 5.1; N, 17.0%]; ν 1720, 2195, 2860, 2930, 2950,
24
21
5
2
max
-
1
3
020, 3060 cm ; δ (400 MHz, DMSO-d ) 7.62 (1H, d, J 9.1 Hz, Ar), 7.58-7.17 (9H, m, Ar), 5.34 and 4.87 (1H, two d, J 13.2 Hz,
H
6
CH), 5.35 and 4.80 (1H, two d, J 9.8 Hz, CH), 4.24 (1Н, t, J 10.4 Hz, СН), 3.98 and 3.92 (1H, dt, J 10.2 Hz, CH ), 3.46-3.24 (1H, m,
2
CH ), 2.10-1.92 (1H, m, CH ), 1.90-1.68 (2H, m, CH ), 1.67-1.35 (2H, m, CH ), 1.22-1.02 (1H, m, CH ); δ (100.6 MHz, DMSO-d )
2
2
2
2
2
C
6

1
2
ACCEPTED MANUSCRIPT
1
1
73.6 (CO), 171.9 and 171.6 (CO), 160.0 and 154.6 (C), 152.8 and 152.5 (C), 132.2 and 132.0 (C), 129.3 and 129.0 (CH), 128.9 and
28.8 (CH), 128.7 and 128.6 (CH), 128.3 and 127.8 (CH), 127.3 and 127.2 (CH), 121.4 and 121.1 (CH), 115.6 and 114.8 (C), 103.7
and 101.0 (CN), 66.5 and 65.9 (CH), 53.7 and 52.6 (CH), 48.7 and 46.0 (CH ), 43.7 and 42.7 (CH), 28.9 and 28.6 (CH ), 24.1 and
2
2
+
2
3.7 (CH ), 23.0 and 22.8 (CH ); m/z (I, %): 411 (34, М ).
2
2
4
.2.15. 2-(1,3-Dioxo-2-phenyl-6,7,8,9,9a,9b-hexahydro-3aH-pyrrolo[3,4-a]indolizin-4-ylidene)-2-[(4-methoxyphenyl)azo]
acetonitrile (11d). From 7d and 2b (0.085 g, 64%), from 8d and 2b (0.090 g, 68%), from 9d and 2b (0.075 g, 58%) as a yellow solid,
o
m.p. 264-265 C; Mixture of isomers (2:3); [Found: C, 67.9; H, 5.2; N, 15.8. C H N O requires C, 68.01; H, 5.25; N, 15.90%]; ν
25
23
5
3
max
-
1
1
7
720, 2200, 2840, 2860, 2930, 2960, 3060 cm ; δ (400 MHz, DMSO-d ) 7.61 (1H, d, J 9.0 Hz, Ar), 7.53-7.48 (4H, m, Ar), 7.37-
.32 (2H, m, Ar), 7.02 and 6.97 (2H, two d, J 9.0 Hz, Ar), 5.34 and 4.77 (1H, two d, J 12.8 Hz, CH), 5.26 and 4.78 (1H, two d, J 8.2
H
6
Hz, CH), 4.24 (1Н, t, J 10.3 Hz, CH), 3.99 and 3.93 (1H, two dd, J 9.3, 10.6 Hz, CH ), 3.80 and 3.78 (3Н, two s, OMe), 3.40-3.30
2
(
1H, m, CH ), 2.07-1.98 (1H, m, CH ), 1.94-1.85 (1H, m, CH ), 1.84-1.76 (1H, m, CH ), 1.68-1.50 (2H, m, CH ), 1.42-1.30 (1H, m,
2 2 2 2 2
CH ); δ (100.6 MHz, DMSO-d ) 173.5 (CO), 172.0 and 171.6 (CO), 159.3 and 159.1 (C), 159.8 and 153.5 (C), 147.1 and 146.7 (C),
2
C
6
1
32.3 (C) and 132.1, 128.9 and 128.8 (CH), 128.7 and 128.6 (CH), 127.2 and 127.1 (CH), 122.9 and 122.7 (CH), 115.7 and 114.8
(
4
C), 114.5 and 114.1 (CH), 103.6 and 100.9 (C), 66.1 and 65.6 (CH), 55.4 and 55.3 (OMe), 53.4 and 52.3 (CH), 48.7 and 45.9 (CH ),
3.7 and 42.8 (CH), 28.9 and 28.6 (CH ), 24.1 and 23.8 (CH ), 23.0 and 22.9 (CH ); m/z (I, %): 441 (42, М ).
2 2 2
2
+
4
.2.16. 2-(7,9-Dioxo-8-phenyl-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]oxazin-6-ylidene)-2-[(4-
o
nitrophenyl)azo]acetonitrile (11e). From 7e and 2b (0.125 g, 92%) as an orange solid, m.p. 306-307 C; The mixture of four isomers
in ratio 10:4:2:1; [Found: C, 60.3; H, 4.0; N, 18.2. C H N O requires C, 60.26; H, 3.96; N, 18.33%]; ν 1720, 2200, 2850, 2920,
2
23
18
6
5
max
-
1
960, 3070 cm ; δ (400 MHz DMSO-d ) 8.23, 7.87, 8.23, 7.82, 8.23, 7.70, 8.23 and 7.41 (4H, four AA'XX', J 8.7 Hz, Ar), 7.55-7.25
H
6
(5Н, m, Ar), 5.42 and 5.31 and 5.16 and 5.06 (four d, 1H, J 9.3 Hz, CH), 4.93 and 4.85 and 4.76 and 4.70 (1H, four d, J 9.0 Hz, CH),
4
.43 (1Н, dt, J 9.5, 4.3 Hz, СН), 4.27-4.11 (1H, m, CH ), 4.10-3.88 (2H, m, CH ), 3.82-3.56 (2H, m, CH ), 3.55-3.39 (m, 1H, CH );
2
2
2
2
δ (100.6 MHz, DMSO-d ) 174.3 (CO), 172.6 and 171.9 (CO), 161.4 and 156.4 (CH), 152.0 and 151.6 (CH), 132.8 (C), 132.6 and
C
6
1
32.6 (C), 132.4 and 132.3 (C), 129.8 and 129.6 (CH), 129.5 and 129.4 (CH), 129.3 and 129.2 (CH), 127.6 and 127.5 (CH), 123.5
and 123.3 (CH), 116.1 and 115.2 (C), 104.5 and 101.5 (C), 70.1 and 69.3 (CH ), 54.8 and 53.7 (CH ), 50.4 and 48.0 (CH), 44.4 and
2
2
+
4
3.7 (CH), 30.6 and 30.5 (CH ), 28.2 and 28.0 (CH). m/z (I, %): 458 (40, М ).
2
4
.2.17.
2-(7,9-Dioxo-8-phenyl-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]oxazin-6-ylidene)-2-[(4-methoxyphenyl)
o
azo]acetonitrile (11f). From 7f and 2b (0.89 g, 67%) as a yellow solid, m.p. 249-250 C; Mixture of isomers (7:3); [Found: C, 65.1;
H, 4.8; N, 15.6. C H N O requires C, 65.00; H, 4.77; N, 15.79%]; δ (400 MHz, DMSO-d ) 7.70-7.57, 7.55-7.45 and 7.20-7.10
24
21
5
4
H
6
(9Н, three m, Ar), 5.20 and 4.87 (1H, two d, J 9.8 Hz, CH), 4.56 and 4.00 (1H, two d, J 11.4 Hz, CH), 4.28 (1Н, dt, J 11.2, 3.2 Hz,
СН), 4.17-4.09 (1H, m, CH ), 3.94-3.86 (2H, m, CH ), 3.80 (3Н, s, ОМе), 3.64-3.50 (2H, m, CH ), 3.35-3.28 (1H, m, CH ); m/z (I,
2
2
2
2
+
%
): 443 (30, М ).
4
.2.18. 2-(1,3-Dioxo-2-phenyl-3a,6,7,8,9,10,10a,10b-octahydropyrrolo[1,2]pyrrolo[3,5-a]azepin-4-ylidene)-2-[(4-
o
nitrophenyl)azo]acetonitrile (11g). From 7g and 2b (0.120 g, 86%) as an orange solid, mp 258-259 C; Mixture of two isomers (1:2);
-
1
[
Found: C, 63.6; H, 4.5; N, 18.1. C H N O requires C, 63.82; H, 4.71; N, 17.86%]; ν 1720, 2200, 2850, 2910, 2970 cm ; δ (400
25 22 6 4 max H
MHz DMSO-d ) 8.27, 7.67, 8.25 and 7.83 (4H, two AA'XX', J 8.8 Hz, Ar), 7.54-7.40 (3Н, m, Ar), 7.33-7.26 (2Н, m, Ar), 5.48 and
6
5
1
.00 (1H, two d, J 9.6 Hz, CH), 4.83-4.71 (1H, m, CH), 4.57 and 4.44 (1Н, two dt, J 3.6, 14.0 Hz, СН), 4.04 and 3.99 (1Н, two t, J
0.4 Hz, СН), 3.77-3.64 (1Н, m, CH ), 2.19-2.09 (1Н, m, CH ), 2.08-1.85 (3Н, m, CH ), 1.81-1.62 (3H, m, CH ), 1.55-1.34 (1H, m,
2
2
2
2
CH ); δ (100.6 MHz, DMSO-d ) 173.8 (CO), 171.2 and 171.0 (CO), 162.6 and 157.3 (C), 157.0 and 156.9 (C), 145.7 and 145.6
2
c
6
(C),132.9 and 132.1 (C), 129.1 and 129.0 (CH), 128.9 and 128.8 (CH), 127.1 and 127.0 (CH), 127.1 and 124.8 (CH), 121.7 and 122.0
(
2
CH), 115.1 and 114.2 (C), 105.3 and 102.3 (C), 70.2 and 69.5 (CH), 54.7 and 53.5 (CH), 50.4 and 47.9 (CH ), 43.7 and 43.0 (CH),
2
+
9.7 and 29.5 (CH ), 27.7 and 27.5 (CH ), 26.6 and 25.9 (CH ), 23.8 and 23.5 (CH ); m/z (I, %): 470 (12, М ).
2
2
2
2
4
.2.19. 2-[(4-Chlorophenyl)azo]-2-(1,3-dioxo-2-phenyl-3a,6,7,8,9,10,10a,10b-octahydropyrrolo[1,2]pyrrolo[3,5-a]azepin-4-
o
ylidene)acetonitrile (11h). From 7h and 2b (0.107 g, 78%) as a yellow solid, m.p. 166-167 C; Mixture of isomers (2:3); [Found: C,
6
-
1
5.0; H, 4.8; N, 15.4. C H ClN O requires C, 65.29; H, 4.82; N, 15.23%]; ν 1720, 2200, 2850, 2920 cm ; δ (400 MHz, DMSO-
25 22 5 2 max H
d6) 7.65-7.16, 7.56-7.42, 7.32-7.27 (9H, m, Ar), 5.47 and 4.94 (1H, two d, J 9.6 Hz, CH), 4.76-4.66 (1H, m, CH), 4.51 and 4.34 (1Н,
two dt, J 4.4, 13.6 Hz, СН), 4.08-3.85 (1Н, m, CH ), 3.70-3.57 (1Н, m, CH ), 2.10-2.07 (1Н, m, CH ), 2.00-1.77 (3H, m, CH ), 1.72-
2
2
2
2
1
.55 (3H, m, CH ), 1.45-1.22 (1H, m, CH ); δ (100.6 MHz, DMSO-d ) 174.4 (CO), 172.0 and 171.8 (CO), 161.7 and 156.1 (C),
2 2 C 6
1
1
5
%
52.1 and 151.9 (C), 132.7 and 132.6 (C), 132.4 and 132.3 (C), 129.8 and 129.6 (CH), 129.5 and 129.4 (CH), 129.3 and 129.2 (CH),
27.6 and 127.5 (CH), 123.5 and 123.2 (CH), 116.1 and 115.2 (CN), 104.5 and 101.4 (C), 70.0 and 69.3 (CH), 54.8 and 53.7 (CH),
0.4 and 48.0 (CH ), 44.4 and 43.7 (CH), 30.5 and 30.4 (CH ), 28.2 and 28.0 (CH ), 27.1 and 26.4 (CH ), 24.4 and 24.0 (CH ); m/z (I,
2
2
2
2
2
+
): 459 (13, М ).
4
.2.20. 2-(7,9-Dioxo-8-phenyl-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]thiazin-6-ylidene)-2-[(4-
o
nitrophenyl)azo]acetonitrile (11i). From 7i and 2b (0.095 g, 67%) as an orange solid, m.p. 299-300 C; Mixture of isomers (3:7);
-
1
[
Found: C, 58.3; H, 3.7; N, 17.5. C H N O S requires C, 58.22; H, 3.82; N, 17.71%]; ν 1715, 2200, 2915 cm ; δ (400 MHz,
23 18 6 4 max H
DMSO-d ) 8.26, 8.23, 7.83 and 7.69 (4H, two АА'ХХ', J 8.8 Hz, Ar), 7.51-7.33 (5Н, m, Ar), 5.57 (1Н, dt, J 10.8, 2.8 Hz, СН), 5.65
6
and 5.26 (1Н, two dt, J 3.2, 13.6 Hz, СН), 5.40 and 4.92 (1H, two d, J 9.2 Hz, CH), 4.12 and 4.06 (1Н, two t, J 10.0 Hz, СН ), 3.63
2
(
1Н, t, J 12.8 Hz, СН ), 3.18-3.06 (1H, m, CH ), 3.00 (1H, t, J 12.0 Hz, CH ), 2.90-2.83 (1H, m, CH ), 2.76-2.66 (1H, m, CH ); δ
2 2 2 2 2 c
(
100.6 MHz, DMSO-d ) 174.2 (CO), 172.7 and 172.6 (CO), 161.9 and 156.2 (C), 152.0 and 151.6 (C), 133.2 and 132.7 (C), 129.4
6
and 129.3 (CH), 128.1 (CH), 127.9 and 127.8 (CH), 127.0 and 126.9 (CH), 126.7 and 126.6 (CH), 122.5 and 122.2 (CH), 114.9 (C),

1
3
ACCEPTED MANUSCRIPT
05.0 and 102.5 (C), 67.2 and 66.8 (CH), 53.2 and 52.2 (CH), 49.2 and 43.6 (CH ), 40.7 and 40.5 (CH), 29.8 and 29.5 (CH ), 25.7
2 2
+
1
and 25.6 (CH); m/z (I, %): 474 (41, М ).
4
.2.21. 2-(7,9-Dioxo-8-phenyl-1,3,4,6a,9a,9b-hexahydropyrrolo[1,2]pyrrolo[3,5-a][1,4]thiazin-6-ylidene)-2-[4-
o
(trifluoromethyl)phenylazo]acetonitrile (11j). From 7k and 2b (0.090 g, 60%) as a yellow solid; mp 272-273 C; Mixture of isomers
(
7:3); [Found: C, 58.0; H, 3.5; N, 14.1. C H F N O S requires C, 57.94; H, 3.65; N, 14.08%]; δ (400 MHz DMSO-d ) 8.50-7.64
24
18
3
5
2
H
6
(4H, m, Ar), 7.53-7.35 (5H, m, Ar), 5.68 and 5.23 (1H, two dt, J 2.0, 12.4 Hz, СН), 5.37 and 4.88 (1H, two d, J 9.6 Hz, CH), 4.53
(
1H, dt, J 10.6, 2.8 Hz, СН), 4.10 and 4.04 (1H, two t, J 10.4 Hz, СН ), 3.60 (1H, t, J 12.8 Hz, СН ), 3.18-3.06 (1H, m, CH ), 3.02-
2
2
2
2
1
1
.92 (1H, m, CH ), 2.88-2.81 (1H, m,CH ), 2.75-2.65 (1H, m, CH ); δ (100.6 MHz, DMSO-d ) 173.5 (CO), 171.6 and 171.4 (CO),
2 2 2 c 6
62.4 and 157.0 (C), 155.8 (C),132.8 and 129.2 (C), 129.4 and 129.3 (CH), 128.1 (CH), 127.9 and 127.8 (CH), 127.0 and 126.9 (CH),
26.7 and 126.6 (CH), 122.5 and 122.2 (CH), 114.9 (C), 105.0 and 102.5 (C), 68.1 and 67.6 (CH), 53.8 and 52.7 (CH), 52.1 and 49.5
(
CH ), 44.7 and 43.9 (CH), 29.8 and 29.6 (CH ), 26.1 and 25.6 (CH); δ (100 MHz, DMSO-d ): -61.80 and -61.65 (two s, 3F, CF );
2 2 F 6 3
+
MS m/z (I, %): 497 (М , 35).
Acknowledgements
JOS personally thanks Prof. Arvi Rauk (University of Calgary, Canada) for assistance. JOS also thanks Compute Canada - Calcul
Canada and Western Canada Research Grid for provided computational resources. Vasiliy Bakulev thanks State task of Ministry
Education No 4.1626.2014/K.
Supplementary Data
Supplementary Data related to this article can be found at http://
1
. References and notes
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7
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ACCEPTED MANUSCRIPT
S1
Supplementary Data
1
,3-Dipolar Сycloaddition of 3-Alkylsulfanyl-2-arylazo-3-
(
tert-cycloalkylamino)acrylonitriles with N-Methyl- and N-
Phenylmaleimides
a
a
a
a
Nataliya P. Belskaya , Svetlana G. Lesogorova , Julia O. Subbotina , Aleksandr V. Koksharov , Pavel A.
b
c
a
Slepukhin , Wim Dehaen and Vasiliy A. Bakulev
a
Urals Federal University, 620002 Ekaterinburg, Mira Str. 19, Russia
b
I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of Russian Academy of Sciences, 20 S.
Kovalevskaya Str., Ekaterinburg 620219, Russia
c
Department of Chemistry, K.U. Leuven, Celestijnenlaan 200F, B-3001, Leuven, Belgium
Contents
Page
S1
Synthesis of alkylsulfanylarylazoacrylonitriles 7,8,9
1
13
Spectra H and C NMR of 3 alkylsulfanylarylazoacrylonitriles 7,8,9
S4
1
13
Spectra H and C NMR for compounds 10 and 11
S26
General
1
13
Melting points were determined with a Stuart SMP3 apparatus. Н NMR and C NMR spectra were recorded on
1
13
a Bruker Avance II (400 MHz for H and 100.6 MHz for C) spectrometer using DMSO-d and CDCl as
6
3
1
13
solvents. Chemical shifts (δ) have been reported in parts per million (ppm) relative to TMS in H and C spectra.
Coupling constants (J) values given in Hertz. Mass spectra were performed on a «SHIMADZU GCMS-QP2010
o
Ultra» mass spectrometer using the electron impact ionization technique (40-200 C, 70 eV). The IR data have
been recorded on a Bruker Alpha (NPVO, ZnSe) IR-Fur spectrometer. Elemental analyses were carried out using a
CHNS/O analyzer Perkin-Elmer 2400 Series II instrument.
1
-3
S,N-acetals 7-9 were prepared by the procedure reported in our previous articles.
3
-Methylsulfanyl-2-[(4-nitrophenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (7a). Red solid (218 mg, 66%), m.p.
1
47-148 ºC; [Found: С, 54.53, Н, 5.31, N, 20.9. C H N O S requires С, 54.37, Н, 5.17, N, 21.13%]; δ (400
1
5
17
5
2
H
MHz, CDCl ) 8.28 and 7.69 (4H, AA'ХХ', J 9.2 Hz, Ar), 3.99-3.81 (4H, m, CH ), 2.60 (3H, s, SMe), 1.81-1.59
3
2
+
(
6H, m, CH ); m/z (I, %): 331 (6, М ).
2
3
-Allylsulfanyl-2-[(4-nitrophenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (8a). Red solid (293 mg, 82%), m.p. 141-
1
42 ºC; [Found: С, 57.11, Н, 5.12, N, 19.41. C H N O S requires С, 57.13, Н, 5.36, N, 19.59%]; δ (400 MHz,
1
7
19
5
2
H
CDCl ) 8.29 and 7.70 (4H, AA'ХХ', J 9.0 Hz, Ar), 5.95-5.82 (1H, m, CH), 5.21 (1H, d, J 16.8 Hz, CHCH ), 5.16
3
2
(
%
1H, d, J 9.2 Hz, CHCH ), 3.99-3.91 (4H, m, CH ), 3.74 (2H, d, J 7.2 Hz, SСН ), 1.81-1.69 (6H, m, CH ); m/z (I,
): 357 (3, М ).
2 2 2 2
+

ACCEPTED MANUSCRIPT
S2
2
-[(4-Nitrophenyl)azo]-3-(1-piperidyl)-3-prop-2-ynylsulfanyl-prop-2-enenitrile (9a). Red solid (323 mg, 91%),
m.p. 140-141 ºC; [Found: С, 57.33, Н, 4.75, N, 19.55. C H N O S requires С, 57.45, Н, 4.82, N, 19.70%]; δ
1
7
17
5
2
H
(
400 MHz, CDCl ) 8.29 and 7.71 (4H, AA'ХХ', J 9.2 Hz, Ar), 3.96 (2Н, d, J 2.5 Hz, SСН ), 3.94-3.81 (4H, m,
3 2
+
CH ), 3.44 (1H, t, J 2.8 Hz, CH), 1.84-1.65 (6H, m, CH ); m/z (I, %): 355 (17, М ).
2
2
2
-[(4-Chlorophenyl)azo]-3-methylsulfanyl-3-(1-piperidyl)prop-2-enenitrile (7b). Yellow solid (288 mg, 90%),
m.p. 141-142 ºC; [Found: С, 56.00, Н, 5.15, N, 17.65. C H ClN S requires С, 56.15, Н, 5.34, N, 17.46%]; δ
1
5
17
4
H
(
1
400 MHz, CDCl ) 7.55 and 7.49 (4H, AA'ХХ', J 8.9 Hz, Ar), 3.89-3.80 (4H, m, CH ), 2.55 (3H, s, SMe), 1.80-
3 2
+
.65 (6H, m, CH ); m/z (I, %): 320 (17, М ).
2
3
-Allylsulfanyl-2-[(4-chlorophenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (8b). Orange solid (315 mg, 91%), m.p.
1
26-127 ºC; [Found: С, 58.61, Н, 5.34, N, 16.11. C H ClN S requires С, 58.86, Н, 5.52, N, 16.15%]; δ (400
1
7
19
4
H
MHz, CDCl ) 7.55 and 7.50 (4H, AA'ВВ', J 8.8 Hz, Ar), 5.95-5.79 (1H, m, CH), 5.19 (1H, d, J 16.8 Hz, CHCH ),
3
2
5
.15 (1H, d, J 10.0 Hz, CHCH ), 3.93-3.81 (4H, m, CH ), 3.68 (2H, d, J 7.2 Hz, SСН ), 1.82-1.67 (6H, m, CH );
2 2 2 2
+
m/z (I, %): 346 (10, М ).
2
-[(4-Chlorophenyl)azo]-3-(1-piperidyl)-3-prop-2-ynylsulfanyl-prop-2-enenitrile (9b). Orange solid (289 mg,
8
4%), m.p. 125-126 ºC; [Found: С, 59.15, Н, 5.11, N, 16.29. C H ClN S requires С, 59.21, Н, 4.97, N, 16.25%];
1
7
17
4
δ (400 MHz, CDCl ) 7.53 and 7.49 (4H, AA'ВВ', J 8.9 Hz, Ar), 3.82 (2Н, d, J 2.7 Hz, SСН ), 3.81-3.72 (4H, m,
H
3
2
+
CH ), 3.27 (1H, t, J 2.7 Hz, CH), 1.79-1.63 (6H, m, CH ); m/z (I, %): 344 (8, М ).
2
2
3
-Methylsulfanyl-2-(phenylazo)-3-(1-piperidyl)prop-2-enenitrile (7c). Yellow solid (237 mg, 83%), m.p. 123-124
CN
ºC; [Found: С, 62.78, Н, 6.53, N, 19.66. C H N S requires С, 62.91, Н, 6.33, N, 19.56%]; δ (400
15 18 4 H
S
N
N
Me
N
MHz, CDCl ) 7.56 (2Н, d, J 7.2 Hz, Ph), 7.45 (2Н, t, J 7.6 Hz, Ph), 7.34 (1H, t, J 7.6 Hz, Ph), 4.00-
3
+
3
.85 (4H, m, CH ), 2.63 (3H, s, SMe), 1.85-1.59 (6H, m, CH ); m/z (I, %): 286 (9, М ).
2
2
3-Allylsulfanyl-2-(phenylazo)-3-(1-piperidyl)prop-2-enenitrile (8c). Orange solid (278 mg, 89%), m.p. 124-125 º;
[
(
Found: С, 65.23, Н, 6.57, N, 18.02. C H N S requires С, 65.35, Н, 6.45, N, 17.93%]; δ (400 MHz, CDCl ) 7.56
2Н, d, J 7.2 Hz, Ph), 7.45 (2Н, t, J 7.6 , Ph), 7.34 (1H, t, J 7.6 Hz, Ph), 5.96-5.80 (1H, m, CH), 5.21 (1H, d, J 16.7
17 20 4 H 3
Hz, CHCH ), 5.15 (1H, d, J 10.0 Hz, CHCH ), 3.95-3.78 (4H, m, CH ), 3.67 (2H, d, J 7.2 Hz, SСН ), 1.85-1.65
2
2
2
2
+
(
6H, m, CH ); m/z (I, %): 312 (9, М ).
2
2
-(Phenylazo)-3-(1-piperidyl)-3-prop-2-ynylsulfanyl-prop-2-enenitrile (9c). Orange solid (223 mg, 72%), m.p.
1
24-125 ºC; [Found: С, 65.62, Н, 5.75, N, 18.14. C H N S requires С, 65.78, Н, 5.84, N, 18.05%]; δ (400 MHz,
1
7
18
4
H
CDCl ) 7.57 (2Н, d, J 8.8 Hz, Ar), 7.47 (2Н, t, J 7.2 Hz, Ph), 7.37 (1H, t, J 7.2 Hz, Ph), 3.90 (2Н, d, J 2.6 Hz,
3
+
SСН ), 3.88-3.81 (4H, m, CH ), 3.41 (1H, t, J 2.6 Hz, CH), 1.81-1.68 (6H, m, CH );m/z (I, %): 310 (13, М ).
2
2
2
2
-[(4-Methoxyphenyl)azo]-3-methylsulfanyl-3-(1-piperidyl)prop-2-enenitrile (7d). Yellow solid (259 mg, 82%),
m.p. 125-126 ºC; [Found: С, 60.48, Н, 6.34, N, 17.59. C H N OS requires С, 60.73, Н, 6.37, N, 17.71%]; δ
1
6
20
4
H
(
(
400 MHz, CDCl ) 7.54 and 7.01 (4H, AA'ХХ', J 9.2 Hz, Ar), 3.80 (3H, s, OМе), 3.81-3.74 (4H, m, СН ), 2.52
3
2
+
3Н, s, SMe), 1.77-1.66 (6H, m, CH ); m/z (I, %): 316 (12, М ).
2
3
-Allylsulfanyl-2-[(4-methoxyphenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (8d). Orange solid (253 mg, 74%), m.p.
1
06-107 ºC; [Found: С, 63.05, Н, 6.65, N, 16.39. C H N ОS requires С, 63.13, Н, 6.48, N, 16.36%]; δ (400
1
8
22
4
H
MHz, CDCl ) 7.54 and 7.02 (4H, AA'ХХ', J 8.9 Hz, Ar), 5.94-5.80 (1H, m, CH), 5.21 (1H, d, J 16.6 Hz, CHCH ),
3
2
5
1
.15 (1H, d, J 10.0 Hz, CHCH ), 3.80 (3H, s, OМе), 3.79-3.76 (4H, m, СН ), 3.64 (2H, d, J 7.1 Hz, SСН ), 1.77-
2 2 2
+
.65 (6H, m, CH ); m/z (I, %): 342 (7, М ).
2
(2-[(4-Methoxyphenyl)azo]-3-(1-piperidyl)-3-prop-2-ynylsulfanyl-prop-2-enenitrile (9d). Orange solid (229 mg,
6
7%), m.p. 106-107 ºC; [Found: С, 63.36, Н, 6.02, N, 16.58. C H N ОS requires С, 63.50, Н, 5.92, N, 16.46%];
1
8
20
4
δ (400 MHz, CDCl ) 7.56 and 7.02 (4H, AA'ХХ', J 8.8 Hz, Ar), 3.81 (2H, d, J 2.5 Hz, SСН ), 3.79-3.76 (4H, m,
H
3
2
+
СН ), 3.64 (1H, t, J 2.5 Hz, CH), 1.79-1.67 (6H, m, CH ); m/z (I, %): 340 (5, М ).
2
2

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3
-Methylsulfanyl-3-morpholino-2-[(4-nitrophenyl)azo]prop-2-enenitrile (7e). Red solid (213 mg, 64%), m.p. 202-
2
03 ºC; [Found: C, 50.65, H, 4.27, N, 21.22. C H N O S requires C, 50.44, H, 4.54, N 21.01%]; δ (400 MHz,
1
4
15
5
3
H
CDCl ) 8.25 and 7.71 (4Н, AA'ХХ', J 9.2 Hz, Ar), 3.98-3.91 (4H, m, СН ), 3.86-3.79 (4H, m, СН ), 2.62 (3H, s,
3
2
2
+
SMe); m/z (I, %): 333 (14, М ).
(2-[(4-Methoxyphenyl)azo]-3-methylsulfanyl-3-morpholino-prop-2-enenitrile (7f). Yellow solid (273 mg, 86%),
m.p. 118-119 ºC; [Found: C, 56.76, H, 5.84, N, 17.40. C H N O S requires C, 56.59, H, 5.70, N, 17.60%]; δ
1
5
18
4
2
H
(
(
400 MHz, CDCl ) 7.54 and 6.94 (4Н, AA'XX', J 8.8 Hz, Ar), 3.82 (3H, s, OMe), 3.90-3.75 (8Н, m, СН ), 2.53
3H, s, SМе); m/z (I, %): 318 (23, М ).
3
2
+
3
-Allylsulfanyl-2-[(3,5-dimethylphenyl)azo]-3-morpholino-prop-2-enenitrile (8e). Orange solid (329 mg, 73%),
m.p. 115-116 ºC; [Found: C, 48.11, H, 3.39, N, 12.36. C H F N OS requires C, 48.00, H, 3.58, N, 12.44%]; δ
1
8
16
6
4
H
(
400 MHz, CDCl ) 8.05 (1Н, s, Ar), 7.70 (1Н, s, Ar), 7.30 (1Н, s, Ar), 5.95-5.85 (1Н, m, СН), 5.27 (1H, dd, J
3
1
6.2, 1.6 , CHCH ), 5.20 (1H, d, J 9.6 Hz, CHCH ), 4.28-4.20 (4H, m, СН ), 3.90-3.82 (4Н, m, СН ), 3.78 (2H, d,
2 2 2 2
+
J 7.2 Hz, SСН ); m/z (I, %): 450 (23, М ).
2
(3-(Azepan-1-yl)-3-methylsulfanyl-2-[(4-nitrophenyl)azo]prop-2-enenitrile (7g). Red solid (242 mg, 70%), m.p.
1
60-161 ºC; [Found: 55.58, H, 5.71, N, 20.02. C H N O S requires C, 55.64, H, 5.54, N, 20.27%]; δ (400 MHz,
1
6
19
5
2
H
CDCl ) 8.26 and 7.68 (4Н, AA'ХХ', J 9.2 Hz, Ar), 3.99-3.89 (4Н, m, СН ), 2.61 (3Н, s, SMe), 1.90-1.82 (4Н, m,
3
2
+
СН ), 1.61-1.54 (4H, m, СН ); m/z (I, %): 345 (2, М ).
2
2
3
-(Azepan-1-yl)-2-[(4-chlorophenyl)azo]-3-methylsulfanyl-prop-2-enenitrile (7h). Yellow solid (301 mg, 92%),
m.p. 108-109 ºC; [Found: C, 57.27, H, 5.81, N,16.51. C H ClN S requires C, 57.39, H, 5.72, N, 16.73%]; δ (400
1
6
19
4
H
MHz, CDCl ) 7.52 and 7.48 (4Н, AA'BB', J 8.8 Hz, Ar), 3.92-3.87 (4Н, m, СН ), 2.57 (3Н, s, SMe), 1.90-1.80
3
2
+
(
4Н, m, СН ), 1.62-1.50 (4H, m, СН ); m/z (I, %): 334 (2, М ).
2
2
3
-Methylthio-2-(4-nitrophenylazo)-3-thiomorpholinoacrylonitrile (7i). Red solid (202 mg, 58%), m.p. 177-178 ºC;
[
Found: C, 47.97, H, 4.12, N, 19.75. C H N O S requires C, 48.12, H, 4.33, N, 20.04%]; δ (400 MHz, CDCl )
14 15 5 2 2 H 3
8
.26 and 7.70 (4Н, AA'ХХ', J 9.0 Hz, Ar), 4.20-4.15 (4Н, m, СН ), 2.90-2.80 (4Н, m, СН ), 2.61 (3H, s, SMe);
2 2
+
m/z (I, %): 349 (4, М ).
3
-Methylsulfanyl-2-[(4-nitrophenyl)azo]-3-thiomorpholino-prop-2-enenitrile (7j). Yellow solid (287 mg, 85%),
m.p. 166-167 ºC; [Found: C, 49.43, H, 4.57, N, 16.27. C H ClN S requires C, 49.62, H, 4.46, N, 16.53%]; δ
1
4
15
4
2
H
(
2
400 MHz, CDCl ) 7.57 and 7.51 (4Н, AA'BB', J 8.8 Hz, Ar), 4.09-4.05 (4Н, m, СН ), 2.87-2.82 (4Н, m, СН ),
3 2 2
.56 (3H, s, SMe); m/z (I, %): 338 (4, М ).
+
3
-Methylsulfanyl-2-[p-tolylazo]-3-thiomorpholino-prop-2-enenitrile (7k). Yellow solid (249 mg, 67%), m.p. 95-96
ºC; [Found: C, 48.11, H, 4.15, N, 14.83. C H F N S requires C, 48.38, H, 4.06, N, 15.04%]; δ (400 MHz,
1
5
15
3
4
2
H
CDCl ) 7.71 (4Н, s, Ar), 4.18-4.11 (4Н, m, СН ), 2.91-2.83 (4Н, m, СН ), 2.59 (3H, s, SMe); m/z (I, %): 372 (10,
3
2
2
+
М ).
References
1
2
3
. Belskaya, N.P.; Koksharov, A.V.; Eliseeva, A.I.; Fan, Z.; Bakulev, V.A. Chem. Heterocycl. Comp., 2011, 47,
64-570.
. Deryabina, T. G.; Belskaya, N. P.; Kodess, M. I.; Dehaen, W.; Toppet, S.; Bakulev, V. A. Tetrahedron Lett.,
006, 47, 1853-1855.
5
2
. Belskaya, N. P.; Bakulev, V. A.; Deryabina, T. G.; Subbotina, J. O.; Kodess, M. I.; Dehaen, W.; Toppet, S.;
Robeyns, K.; Van Meervelt, L. Tetrahedron, 2009, 65, 7662-7672.

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Fig. S1. Spectrum Н NMR 3-methylsulfanyl-2-[(4-nitrophenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (7a) (CDCl )
3

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Fig. S2. Spectrum Н NMR 3-allylsulfanyl-2-[(4-nitrophenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (8a) (CDCl )
3

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13
Fig. S3. Spectrum С NMR 3-allylsulfanyl-2-[(4-nitrophenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (8a) (CDCl )
3

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Fig. S4. Spectrum Н NMR 2-[(4-nitrophenyl)azo]-3-(1-piperidyl)-3-prop-2-ynylsulfanyl-prop-2-enenitrile (9a) (CDCl )
3

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Fig. S5. Spectrum Н NMR 2-[(4-chlorophenyl)azo]-3-methylsulfanyl-3-(1-piperidyl)prop-2-enenitrile (7b) (CDCl )
3

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Fig. S6. Spectrum Н NMR 3-allylsulfanyl-2-[(4-chlorophenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (8b) (CDCl )
3

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1
Fig. S7. Spectrum Н NMR 2-[(4-chlorophenyl)azo]-3-(1-piperidyl)-3-prop-2-ynylsulfanyl-prop-2-enenitrile (9b) (CDCl )
3

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1
Fig. S8. Spectrum Н NMR 3-methylsulfanyl-2-(phenylazo)-3-(1-piperidyl)prop-2-enenitrile (7c) (CDCl )
3

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1
Fig. S9. Spectrum Н NMR 3-allylsulfanyl-2-(phenylazo)-3-(1-piperidyl)prop-2-enenitrile (8c) (CDCl )
3

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13
Fig. S10. Spectrum C NMR 3-allylsulfanyl-2-(phenylazo)-3-(1-piperidyl)prop-2-enenitrile (8c) (CDCl )
3

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1
Fig. S11. Spectrum Н NMR 2-(phenylazo)-3-(1-piperidyl)-3-prop-2-ynylsulfanyl-prop-2-enenitrile (9c) (DMSO-d )
6

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1
Fig. S12. Spectrum Н NMR 2-[(4-methoxyphenyl)azo]-3-methylsulfanyl-3-(1-piperidyl)prop-2-enenitrile (7d) (CDCl )
3

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1
Fig. S13. Spectrum Н NMR 3-allylsulfanyl-2-[(4-methoxyphenyl)azo]-3-(1-piperidyl)prop-2-enenitrile (8d) (CDCl )
3