The mannich reaction in the synthesis of N,S-containing heterocycles 12.* First example of aminomethylation involving 2-thioxonicotinamide derivative: Synthesis of 3,5,7,11-tetraazatricyclo[7.3.1.02,7]tridec- 2-ene-9-carboxamides

Article abstract of DOI:10.1007/s11172-012-0019-4

Piperidinium 6-amino-5-cyano-3-N-(4-methylphenyl)carbamoyl-4-phenyl-1,4- dihydro- pyridine-2-thiolate upon the action of primary amines and excess formaldehyde undergoes aminomethylation to form 3,5,7,11-tetraazatricyclo[7.3.1. 0^2,7]tridec-2-en

Full text of DOI:10.1007/s11172-012-0019-4

Russian Chemical Bulletin, International Edition, Vol. 61, No. 1, pp. 136—140, January, 2012
136
The Mannich reaction in the synthesis of N,Sꢀcontaining heterocycles
12.* First example of aminomethylation involving 2ꢀthioxonicotinamide derivative:
synthesis of 3,5,7,11ꢀtetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀeneꢀ9ꢀcarboxamides
V. V. Dotsenko,a,b S. G. Krivokolysko,a and V. P. Litvinovc†
a"ChemEx" Laboratory Vladimir Dal´ EastꢀUkrainian National University,
20 a kv. Molodezhnyi, 91034 Lugansk, Ukraine.
Eꢀmail: Victor_Dotsenko@bigmir.net
bPhysicoꢀchemical Department, State Enterprise "Luganskstandartmetrology",
50 ul. Timiryazeva, 91021 Lugansk, Ukraine
cN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation
Piperidinium 6ꢀaminoꢀ5ꢀcyanoꢀ3ꢀNꢀ(4ꢀmethylphenyl)carbamoylꢀ4ꢀphenylꢀ1,4ꢀdihydroꢀ
pyridineꢀ2ꢀthiolate upon the action of primary amines and excess formaldehyde undergoes
aminomethylation to form 3,5,7,11ꢀtetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀeneꢀ9ꢀcarboxamides in
36—52% yields.
Key words: the Mannich reaction, pyridineꢀ2ꢀthiolates, aminomethylation, 3,5,7,11ꢀtetraꢀ
azatricyclo[7.3.1.02,7]tridecꢀ2ꢀenes.
2ꢀThioxo(mercapto)ꢀ3ꢀcyanopyridines and related
carboxamides can essentially differ from those for the much
more in detail studied 3ꢀcyanoꢀsubstituted analogs.1 Since
thiolate 1 has at least six nucleophilic centers (C(3), C(5),
NH, NH2, CONHAr, S–) which can undergo aminoꢀ
methylation, its behavior under the Mannich reaction conꢀ
ditions is hardly predictable. The only close example found
by us in the literature is a reaction involving 2ꢀthioxoꢀ
nicotinamide with formaldehyde,9 leading to a mixture of
pyrido[3,2ꢀe][1,3]thiazines (Scheme 2).
Thiolate 1 was synthesized by a multiꢀcomponent conꢀ
densation of benzaldehyde, malononitrile, 3ꢀaminoꢀNꢀ(4ꢀ
methylphenyl)ꢀ3ꢀthioxopropanamide (2), and piperidine.
We found that compound 1 upon treatment with an excess
of 37% aqueous formaldehyde and primary amines in the
absence of a catalyst undergo the aminomethylation reacꢀ
tion at the centers C(3), C(5), NH, and NH2 to form the
DABCNꢀlike structures, viz., 3,5,7,11ꢀtetraazatricycloꢀ
[7.3.1.02,7]tridecꢀ2ꢀeneꢀ9ꢀcarboxamide derivatives 3a—c,
in 36—52% yields instead of the expected, by analogy with
the literature data,9 aminomethylation products at the sulꢀ
fur atom and the C(O)NHAr fragments, i.e., thiazines 4
(Scheme 3). It should be noted that such a reaction has
not been described in the series of 2ꢀthioxonicotinamide
derivatives.
ꢀthiolactams are of significant practical interest due to
a synthetic potential and a wide range of biological activiꢀ
ty of their derivatives.1 They can behave as Cꢀ, Nꢀ, or
Sꢀnucleophiles toward electrophilic agents depending on
both the nature of a substrate and the structure of an
electrophile. In this connection, aminomethylation reacꢀ
tion frequently leading to unpredictable results is of speꢀ
cial interest. Thus, 2ꢀmercaptopyridines or their 2ꢀthioxo
tautomers give in the Mannich reaction 2ꢀ(dialkylaminoꢀ
methylthio)pyridines,2 Nꢀ(dialkylaminomethyl)pyridineꢀ
2(1H)ꢀthiones,3 pyrido[2,1ꢀb][1,3,5]thiadiazines,4 bisꢀ
(pyrido[2,1ꢀb][1,3,5]thiadiazinꢀ7ꢀyl)methanes,5 6ꢀthioxoꢀ
pyrido[1,2ꢀa][1,3,5]triazines,6 3,7ꢀdiazabicyclo[3.3.1]ꢀ
nonanes (DABCN, bispydines),7 and tricyclic structures,
viz., 3,5,7,11ꢀtetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀenes8
(Scheme 1).
In the present work, we made an attempt to study an
aminomethylation reaction of piperidinium 6ꢀaminoꢀ5ꢀ
cyanoꢀ3ꢀNꢀ(4ꢀmethylphenyl)carbamoylꢀ4ꢀphenylꢀ1,4ꢀ
dihydropyridineꢀ2ꢀthiolate (1). Generally, despite availꢀ
ability of 2ꢀmercaptopyridineꢀ3ꢀcarboxamides,9—13 their
properties are studied poorly. Some known examples10,12,13
indicate that reactions of 2ꢀmercapto(thioxo)pyridineꢀ3ꢀ
After filtration, the mother liquor did not yield addiꢀ
tional amount of the product: the residue after evaporaꢀ
tion of the solvent is a yellow resin of a complex composition
presumably containing products of competitive aminoꢀ
methylation involving piperidine. Similarly, treatment
* For Part 11, see V. V. Dotsenko, S. G. Krivokolysko, V. P.
Litvinov, Izv. Akad. Nauk, Ser. Khim., 2012, 129 [Russ. Chem.
Bull., Int. Ed., 2012, 61, 131].
† Deceased.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 134—138, January, 2012.
1066ꢀ5285/12/6101ꢀ136 © 2012 Springer Science+Business Media, Inc.

Tetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀenes
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
137
Scheme 1
X = CN, CO2Alk; Y = O, CH2; R = H, Alk, Ar
Scheme 2
C(4)H2 and C(6)H2 groups; the signals for the C(13)H
protons are found as a sharp singlet at  3.96—4.15. These
data are in good agreement with the chemical shifts for the
related DABCNꢀlike structures.8
The structure of compound 3b was confirmed by
a combination of 2D NMR experiments with the
1
1H—13C HSQC and H—13C HMBC heteronuclear corꢀ
relations (Fig. 1, 2). In the HMBC spectrum, the presence
of the crossꢀpeaks between the C=S group peak ( 200.50)
and the dd at  5.77 from the one hand and the doublet at
 3.70 from the other hand enables an unambiguous asꢀ
signment of the latter to the signals for the protons of the
C(6)H2 and C(10)H2 groups, respectively. A HSQC
method makes it possible to unambiguously assign the
signals for the 13C and 1H nuclei of the C(4)H2, C(12)H2,
and C(13)H fragments. The presence of correlations beꢀ
tween the signal at  50.63 (C(13)) and the pair of dd
C(10)H2 and C(12)H2, as well as between the singlet for
the proton C(13)H ( 3.97) and the peaks at  58.644
(C(12)), 62.887 (C(10)), 116.238 (CN), and 200.50
(C=S) in the 1H—13C HMBC spectrum excludes alternaꢀ
tive interpretations and confirms the 3,5,7,11ꢀtetraꢀ
azatricyclo[7.3.1.02,7]tridecꢀ2ꢀene structure suggested for
compound 3b.
The IR spectra of compounds 3a—c do not contain
absorption bands of the conjugated cyano groups at
 = 2200 30 cm–1, exhibiting weak absorption bands at
 = 2250 cm–1 instead, which correspond to the stretchꢀ
ing vibrations of the unconjugated CN group. Absorption
bands in the region  = 3425–3430 cm–1 and strong bands
at  = 1645—1650 and 1675—1690 cm–1 should be attriꢀ
of thiolate 1 with formaldehyde in the absence of a primaꢀ
ry amine in EtOH or AcOH leads to the resinification of
the reaction mixture and formation of a complex mixture
of products of unknown structure (TLC, LC/MS).
Compounds 3 are pale yellow finely crystalline powꢀ
ders, readily soluble in DMSO and DMF, moderately solꢀ
uble in hot acetone, and insoluble in EtOH. The structure
of compounds 3a—c was confirmed by the spectral data.
Thus, two pairs of doublets at  3.07—4.26 (2J =
= 10.30—11.75 Hz) corresponding to the methylene proꢀ
tons C(12)H2 and C(10)H2 are found in the 1H NMR
spectra. Two pairs of doublets with very pronounced "roof
effect" (AB system) in the low field ( 4.34—5.31,
2J = 16.6—17.1 Hz;  5.23—5.99, 2J = 12.5—13.7 Hz)
should be attributed to the signals for the protons of the

138
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Dotsenko et al.
Scheme 3
R = 4ꢀMeC6H4 (1–3)
3: R´ = Ph (a), 4ꢀMeC6H4 (b), CH2Ph (c)
buted to the stretching vibrations of the NHR, C=N, and
C=O groups, respectively.
were found. The new reaction is characterized by preparaꢀ
tive simplicity, gives acceptable yields of the target prodꢀ
ucts, and can serve as a convenient protocol for the prepaꢀ
ration of combinatorial libraries.
It should be noted that the 3ꢀcarbonitrile analogs of
compound 1 behave similarly under conditions of aminoꢀ
methylation reaction. It can be suggested that formation
of 3,5,7,11ꢀtetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀenes upon
treatment of 3,5ꢀdisubstituted 6ꢀaminoꢀ1,4ꢀdihydroꢀ
pyridineꢀ2ꢀthiolates with the primary amine—HCHO sysꢀ
tem is of fairly general character, with the amino group at
In conclusion, piperidinium 6ꢀaminoꢀ5ꢀcyanoꢀ3ꢀNꢀ
(4ꢀmethylphenyl)carbamoylꢀ4ꢀphenylꢀ1,4ꢀdihydropyrꢀ
idineꢀ2ꢀthiolate under the Mannich reaction conditions
undergo aminomethylation at C(3), C(5), NH, and NH2
to form the earlier unknown compounds, 3,5,7,11ꢀtetraꢀ
azatricyclo[7.3.1.02,7]tridecꢀ2ꢀeneꢀ9ꢀcarboxamide derivꢀ
atives, promising polydentate ligands and new objects for
bioscreening. Contrary to our expectations, no products
of aminomethylation at the sulfur atom and C(O)NHAr

2
20
{3.87, 47.05}
{3.87, 50.15}
{3.90, 46.98}
40
{5.84, 64.49}
{4.94, 65.02}
{5.84, 64.49}
{5.84, 64.49}
{4.98, 64.88}
{5.21, 64.95}
60
{3.68, 62.38}
{3.97, 62.22}
{4.11, 62.26}
{5.72, 64.43}
80
{3.91, 62.29}
100
120
140
160
180
200
{3.97, 115.79}
{5.17, 145.47}
{3.97, 135.15}
{3.96, 145.89}
{3.98, 135.15}
{3.98, 145.90}
{5.84, 143.64}
{5.21, 145.45}
{5.75, 143.62}
{5.75, 200.10}
{3.97, 164.56}
{4.99, 145.36}
{4.94, 145.46}
{5.81, 143.71}
{5.80, 200.24}
{3.91, 145.98}
{3.70, 200.08}
{3.96, 200.17}
6.1 5.9
5.7 5.5 5.3
5.1 4.9
4.7 4.5 4.3
4.1 3.9
3.7 3.5

1
Fig. 1. The fragment of the HMBC spectrum of compound 3b.

Tetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀenes
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
139

2
46
48
50
52
54
56
58
60
62
64
66
68
70
{3.99, 50.96}
{3.90, 58.98}
{3.92, 58.99}
{3.66, 58.98}
{4.13, 63.22}
{5.18, 65.27}
{4.16, 63.24}
{5.22, 65.29}
{4.95, 65.27}
{5.85, 65.91}
{5.83, 65.89}
{3.72, 63.21}
{4.99, 65.25}
5.8
5.6
5.4
5.2
5.0
4.8
4.6
4.4
4.2
4.0
3.8
3.6

1
Fig. 2. The fragment of the HSQC spectrum of compound 3b.
0…—4 C. A precipitate that formed was filtered off and washed
several times with acetone. The yield was 1.33 g (62%), yellow
finely crystalline powder, m.p. 175—180 C (decomp.). Found (%):
C, 67.16; H, 6.56; N, 15.63. C25H29N5OS (M = 447.61). Calcuꢀ
lated (%): C, 67.09; H, 6.53; N, 15.65. 1H NMR (DMSOꢀd6), :
1.54—1.62 (m, 6 H, (CH2)3); 2.21 (s, 3 H, ArCH3); 2.98 (m, 4 H,
+NH2(CH2)2); 4.66 (s, 1 H, C(4)H); 5.53 (br.s, 2 H, C(6)NH2);
6.99, 7.43 (both d, 2 H each, H3CC6H4, 3J = 8.0 Hz); 7.04—7.20
(m, 5 H, Ph); 7.72 (s, 1 H, C(O)NH); 13.42 (s, 1 H, NHPy). No
signal for the +NH2 protons was found because deuterium exꢀ
change with DMSOꢀd6.
position 6 of dihydropyridine substrate playing a key role
in the formation of a tricyclic system.
Experimental
1
H NMR spectra were recorded on a Bruker DRXꢀ500
(500.13 MHz), Me4Si internal standard. Heteronuclear 1H—13
C
HSQC and HMBC correlation experiments were performed on
a Bruker Avance II 400 spectrometer (400.13 (1H) and 100.62 MHz
(
13C)) in CCl4—DMSOꢀd6, Me4Si internal standard. IR spectra
Synthesis of 3,5,7,11ꢀtetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀ
eneꢀ9ꢀcarboxamides 3a—c (general procedure). Thiolate 1 (0.3 g,
0.67 mmol) was suspended in EtOH (7—8 mL), followed by
addition of excess of 37% aqueous formaldehyde (1.0 mL,
13.3 mmol, free of paraformaldehyde impurities), and the correꢀ
sponding primary amine (2.5 equiv., 1.7 mmol). The mixture
was refluxed for 2—3 min with vigorous stirring and then stirred
for 3—4 h at 20 C. After 48 h, a precipitate that formed was
filtered off and washed with EtOH. For purification, comꢀ
pounds 3 were suspended in the EtOH—acetone (1 : 2) mixꢀ
tures, refluxed for 5 min and cooled. A pale yellow precipitate
was filtered off, washed with EtOH—acetone and dried at 60 C
to obtain analytically pure samples of compounds 3a—c.
1ꢀCyanoꢀNꢀ(4ꢀmethylphenyl)ꢀ5,11,13ꢀtriphenylꢀ8ꢀthioxoꢀ
3,5,7,11ꢀtetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀeneꢀ9ꢀcarboxamide
(3a). The yield was 38%, m.p. 238—240 C (EtOH—acetone),
Rf = 0.80 (acetone—hexane (1 : 1)). Found (%): C, 72.20;
H, 5.43; N, 14.04. C36H32N6OS (M = 596.76). Calculated (%):
C, 72.46; H, 5.41; N, 14.08. IR, /cm–1: 3430 (NH), 2250 (CN),
were recorded on an IKSꢀ29 spectrophotometer in Nujol. Eleꢀ
mental analysis was performed on a Perkin—Elmer C,H,NꢀAnꢀ
alyzer apparatus. Purity of individual compounds was monitored
by TLC on Silufol UVꢀ254 plates, using the acetone—hexane
(1 : 1) system as an eluent and visualization in iodine vapors or
under UV light. Melting points were measured on a Kofler heatꢀ
ing stage and were not corrected. 3ꢀAminoꢀNꢀ(4ꢀmethylphenyl)ꢀ
3ꢀthioxopropanamide (2) was obtained by the reaction of Nꢀ(4ꢀ
methylphenyl)cyanoacetamide with H2S in the pyridine—Et3N
mixture according to the known procedure.10,12
Piperidinium 6ꢀaminolꢀ5ꢀcyanoꢀ3ꢀNꢀ(4ꢀmethylphenyl)carbaꢀ
moylꢀ4ꢀphenyꢀ1,4ꢀdihydropyridineꢀ2ꢀthiolate (1) was synthesized
similarly to the known procedures11b,11d,13b as follows: a mixture
of freshly distilled benzaldehyde (0.5 mL, 4.8 mmol), malonoꢀ
nitrile (0.32 g, 4.8 mmol), and piperidine (1 drop) in EtOH
(3 mL) was stirred for 0.5 h, followed by addition of 3ꢀaminoꢀNꢀ
(4ꢀmethylphenyl)ꢀ3ꢀthioxopropanamide (2) (1.0 g, 4.8 mmol)
and piperidine (0.8 mL, 8.1 mmol). The reaction mixture was
stirred for 3 h at 20 C and kept for 24 h in refrigerator at

140
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 1, January, 2012
Dotsenko et al.
1675 (C=O), 1650 (C=N). 1H NMR (DMSOꢀd6), : 2.21 (s, 3 H,
Usp. Khim., 2006, 75, 645 [Russ. Chem. Rev. (Engl. Transl.),
2006, 75, 645].
2. I. M. Orudzheva, T. E. Efendiev, S. M. Aliev, Zh. Org. Khim.,
1981, 17, 410 [Russ. J. Org. Chem. (Engl. Transl.), 1981,
17, No. 2].
ArCH3); 3.79 (m, 2 H, C(10)H and C(12)H, the overlap of two d);
2
3.99 (d, 1 H, C(12)H, J = 11.25 Hz, a part of the AB system);
4.15 (s, 1 H, C(13)H); 4.26 (d, 1 H, C(10)H, 2J = 11.75 Hz,
a part of the AB system); 5.05, 5.31 (both d, 1 H each, C(4)H2,
2J = 17.1 Hz, AB system); 5.63, 5.99 (both d, 1 H each, C(6)H2,
2J = 13.7 Hz, AB system); 6.86—7.29 (m, 19 H, 4 Ar); 8.11
(s, 1 H, NH).
3. A. Essawy, A. Z. M. Heikal, Pakistan J. Sci. Ind. Res., 1982,
25, No. 5, 153.
4. (a) V. V. Dotsenko, S. G. Krivokolysko, A. N. Chernega,
V. P. Litvinov, Dokl. Akad. Nauk, 2003, 389, 763 [Dokl.
Chem. (Engl. Transl.), 2003, 389, Nos 4—6, 92]; (b) V. V.
Dotsenko, S. G. Krivokolysko, V. P. Litvinov, Monatsh.
Chem., 2008, 139, 271.
5. V. V. Dotsenko, S. G. Krivokolysko, V. P. Litvinov, Moꢀ
natsh. Chem., 2008, 139, 657.
6. V. V. Dotsenko, S. G. Krivokolysko, V. P. Litvinov, Khim.
Geterotsikl. Soedin., 2007, 621 [Chem. Heterocycl. Compd.
(Engl. Transl.), 2007, 43, 517].
7. (a) V. V. Dotsenko, S. G. Krivokolysko, V. P. Litvinov, Khim.
Geterotsikl. Soedin., 2005, 1695 [Chem. Heterocycl. Compd.
(Engl. Transl.), 2005, 41, 1428]; (b) V. V. Dotsenko, S. G.
Krivokolysko, V. P. Litvinov, Monatsh. Chem., 2007, 138,
489; (c) V. V. Dotsenko, S. G. Krivokolysko, V. P. Litvinov,
Izv. Akad. Nauk, Ser. Khim., 2007, 2397 [Russ. Chem. Bull.,
Int. Ed., 2007, 56, 2482].
8. (a) V. V. Dotsenko, S. G. Krivokolysko, V. P. Litvinov, Izv.
Akad. Nauk, Ser. Khim., 2005, 2605 [Russ. Chem. Bull., Int. Ed.,
2005, 54, 2692]; (b) V. V. Dotsenko, S. G. Krivokolysko, A. N.
Chernega, V. P. Litvinov, Monatsh. Chem., 2007, 138, 35;
(c) V. V. Dotsenko, S. G. Krivokolysko, A. N. Chernega, V. P.
Litvinov, Izv. Akad. Nauk, Ser. Khim., 2007, 1014 [Russ.
Chem. Bull., Int. Ed., 2007, 56, 1053]; (d) V. V. Dotsenko, S. G.
Krivokolysko, V. P. Litvinov, Khim. Geterotsikl. Soedin., 2007,
1709 [Chem. Heterocycl. Compd. (Engl. Transl.), 2007, 43,
1455]; (e) V. V. Dotsenko, S. G. Krivokolysko, V. P. Litvinov,
E. B. Rusanov, Dokl. Akad. Nauk, 2007, 413, 345 [Dokl.
Chem. (Engl. Transl.), 2007, 413, No. 1, 68].
1ꢀCyanoꢀN,5,11ꢀtri(4ꢀmethylphenyl)ꢀ13ꢀphenylꢀ8ꢀthioxoꢀ
3,5,7,11ꢀtetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀeneꢀ9ꢀcarboxamide
(3b). The yield was 52%, m.p. 208—210 C (EtOH—acetone),
Rf = 0.81 (acetone—hexane (1 : 1)). Found (%): C, 72.86;
H, 5.83; N, 13.39. C38H36N6OS (M = 624.81). Calculated (%):
C, 73.05; H, 5.81; N, 13.45. IR, /cm–1: 3425 (NH), 2250 (CN),
1685 (C=O), 1650 (C=N). 1H NMR (CCl4—DMSOꢀd6,
400 MHz), : 2.21, 2.24, 2.28 (three s, 3 H each, 3 ArCH3); 3.64,
3.91 (both d, 1 H each, C(12)H2), 2J = 11.2 Hz, AB system);
3.70, 4.13 (both d, 1 H each, C(10)H2, 2J = 11.8 Hz, AB sysꢀ
tem); 3.98 (s, 1 H, C(13)H); 4.97, 5.20 (both d, 1 H each, C(4)H2,
2J = 16.9 Hz, AB system); 5.77 (dd, 2 H, C(6)H2, 2J = 13.6 Hz,
AB system); 6.69—7.01 (m, the overlap of six d, 12 H,
3 C6H4CH3); 7.09—7.16 (m, 4 H, Ph); 7.26 (m, 1 H, Ph); 7.75
(br.s, 1 H, NH). 13C NMR (CCl4—DMSOꢀd6, 100 MHz),
: 20.083 (2 ArCH3); 20.389 (C(O)NHC6H4CH3); 47.628 (C(1));
50.631 (C(13)); 58.644 (C(12)); 62.705 (C(9)); 62.887 (C(10));
64.921 (C(4)); 65.548 (C(6)); 116.238 (CN); 117.247 (CAr);
118.180 (CAr); 120.696 (CAr); 127.928 (CAr); 128.256 (CAr);
128.664 (CAr); 128.781 (CAr); 129.153 (CAr); 129.401 (CAr);
129.612 (CAr); 130.341 (CAr);132.798 (CAr); 134.446 (C(2));
135.569 (CAr); 165.155 (C(O)NH); 200.500 (C=S).
5,11ꢀDibenzylꢀ1ꢀcyanoꢀNꢀ(4ꢀmethylphenyl)ꢀ13ꢀphenylꢀ8ꢀ
thioxoꢀ3,5,7,11ꢀtetraazatricyclo[7.3.1.02,7]tridecꢀ2ꢀeneꢀ9ꢀcarbꢀ
oxamide (3c). The yield was 36%, m.p. 197—199 C
(EtOH—acetone), Rf = 0.80 (acetone—hexane (1 : 1)). Found (%):
C, 73.29; H, 5.80; N, 13.55. C38H36N6OS (M = 624.81). Calcuꢀ
lated (%): C, 73.05; H, 5.81; N, 13.45. IR, /cm–1: 3430 (NH),
2250 (CN), 1690 (C=O), 1645 (C=N). 1H NMR (DMSOꢀd6),
: 2.18 (s, 3 H, ArCH3); 3.07, 3.38 (both d, 1 H each, C(12)H2,
2J = 11.0 Hz, AX system); 3.12, 3.49 (both d, 1 H each, C(10)H2,
2J = 10.3 Hz, AX system); 3.69, 3.82 (both d, 1 H each, NCH2Ph,
2J = 13.70 Hz, AB system); 3.94 (m, 2 H, NCH2Ph); 3.96 (s, 1 H,
C(13)H); 4.39, 4.57 (both d, 1 H each, C(4)H2, 2J = 16.6 Hz,
AB system); 5.23, 5.56 (both d, 1 H each, C(6)H2, 2J = 12.5 Hz,
AX system); 6.89 (dd, 4 H, C6H4CH3, 3J = 8.05 Hz); 7.27—7.42
(m, 15 H, 3 Ph); 7.98 (s, 1 H, NH).
9. A. D. Dunn, R. Norrie, Z. Chem., 1988, 28, No. 6, 212.
10. W. Schaper, Synthesis, 1985, 861.
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Received November 12, 2010;
in revised form October 5, 2011