Intramolecular cyclization of 1-[1-alkylsulfanyl-2-phenyl- 2-(phenylhydrazono)ethylidene]-pyrrolidinium salts

Full text of DOI:10.1007/s10593-010-0647-2

Chemistry of Heterocyclic Compounds, Vol. 46, No. 9, 2010
INTRAMOLECULAR CYCLIZATION
OF 1-[1-ALKYLSULFANYL-2-PHENYL-
2-(PHENYLHYDRAZONO)ETHYLIDENE]-
PYRROLIDINIUM SALTS
N. P. Bel'skaya1*, A. V. Koksharov1, T. G. Deryabina2, and V. A. Bakulev1
Keywords: alkylation, intramolecular cyclization, pyrrolotriazine.
We have discovered that benzyl-, allyl-, and propargylsulfanyl derivatives of pyrrolidinium salts 3
obtained by the alkylation of thioamide 1 in DMF at room temperature in the presence of cesium carbonate may
be converted into 1,3-diphenyl-6,7,8,8a-tetrahydro-1H-pyrrolo[2,1-c]-1,2,4-triazine-4-thione (4) in good yields.
Ph
N
S
Ph
S
R
Ph
N
8a
Ph
S
Cs2CO3, DMF
room temp.,
N
Br
H
+
acetone,
room temp.
H
N
N
N
N
+
RBr
8
N
N
6
3-24 h
Ph
Ph
1
2
4
3
61–66%
87–97%
2, 3 a R = Bn, b R = All, c R = propargyl
The use of other organic or inorganic bases such as triethylamine, DBU, and sodium carbonate or other
solvents such as acetonitrile leads to an increase in the reaction time and a significant decrease in the yield of
thione 4.
We have previously shown that the intramolecular cyclization of 3-allyl- and 3-propargylsulfanyl-
3-(pyrrolidin-1-yl)-2-arylazoacrylonitriles is a new method for the preparation of bicyclic nonaromatic
1,2,4-triazines [1]. The observed transformation of pyrrolidinium salts 3 shows that this reaction is general for
alkyl derivatives of arylhydrazonothioacetamides and considerably expands its scope. The products obtained
hold practical interest for biological investigation since pyrrolotriazines have high antitumor activity [2].
_______
* To whom correspondence should be addressed, e-mail: belska@mail.ustu.ru.
1Ural Federal University named after the First President of Russia B. N. Yeltsin, Yekaterinburg 620002, Russia.
2I Ya. Postovskii Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
Yekaterinburg 620041, GSP-147, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1427-1429, September, 2010.
Original article submitted August 6, 2010.
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0009-3122/10/4609-1156©2010 Springer Science+Business Media, Inc.

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The H and 13C NMR spectra were taken on a Bruker DRX-400 spectrometer at 400 and 100 MHz,
respectively, in DMSO-d6 with TMS as the internal standard. The mass spectra were taken on a Varian
MAT 311A mass spectrometer with direct sample inlet into the source, accelerating voltage 3 kV, and ionizing
electron energy 70 eV.
Synthesis of Alkylsulfanylpyrrolidinium Salts 3a-c (General Method). Alkyl bromide (8.0 mmol) is
added to a solution of hydrazone 1 (0.5 g, 1.6 mmol) in acetone (5 ml). The reaction mixture is maintained for
24 h at room temperature. Then, ether is added. The precipitate is filtered off and washed with ether.
1-[1-Benzylsulfanyl-2-phenyl-2-(2-phenylhydrazono)ethylidene]pyrrolidinium Bromide (3b) was
1
obtained in 97% yield; mp 140-141°C. H NMR spectrum, , ppm (J, Hz): 2.02-2.11 (2H, m, CH2); 2.18-2.28
(2H, m, CH2); 3.64-3.76 (2H, m, NCH2); 4.05-4.11 (2H, m, NCH2); 4.05 and 4.25 (2H, AB system, J = 14.0,
SCH2); 6.96-7.02 (1H, m, C6H5); 7.09-7.16 (5H, m, C6H5); 7.31-7.36 (4H, m, C6H5); 7.43-7.53 (3H, m, C6H5);
7.72 (2H, d, J = 6.8, C6H5); 10.62 (1H, s, NH). Mass spectrum, m/z (Irel, %): 309 [M-C7H7Br]+ (12). Found, %:
C 62.32; H 5.37; N 8.66. C25H26BrN3S. Calculated, %: C 62.50; H 5.42; N 8.75.
1-[1-Allylsulfanyl-2-phenyl-2-(2-phenylhydrazono)ethylidene]pyrrolidinium Bromide (3b) was
obtained in 87% yield; mp 143-144°C. 1H NMR spectrum, , ppm (J, Hz): 2.00-2.46 (4H, m, CH2); 3.63 (2H, d,
J = 6.9, SCH2); 3.65-3.98 (2H, m, NCH2); 3.98-4.20 (1H, m, NCH2); 4.24-4.45 (1H, m, NCH2); 5.05 (1H, d,
J = 10.4, CH2 allyl); 5.19 (1H, d, J = 16.8, CH2 allyl); 5.52-5.81 (1H, m, CH allyl); 6.93 (1H, t, J = 6.8, C6H5);
7.27 (2H, d, J = 7.8, C6H5); 7.33-7.50 (3H, m, C6H5); 7.59 (2H, d, J = 7.8, C6H5); 7.71 (2H, d, J = 8.2, C6H5);
11.09 (1H, s, NH). Mass spectrum, m/z (Irel, %): 309 [M-C2H5Br]+ (21). Found, %: C 58.54; H 5.51; N 9.67.
C21H24BrN3S. Calculated, %: C 58.60; H 5.58; N 9.77.
1-[1-(Prop-2-inylsulfanyl)-2-phenyl-2-(2-phenylhydrazono)ethylidene]pyrrolidinium Bromide (3c)
1
was obtained in 89% yield; mp 150-151°C. H NMR spectrum, , ppm (J, Hz): 2.02-2.39 (4H, m, CH2); 2.92
(1H, t, J = 2.4, CH); 3.65-3.93 (2H, m, NCH2); 3.78 and 3.81 (2H, AB system, J = 17.0, SCH2); 4.00-4.20 (1H,
m, NCH2); 4.21-4.40 (1H, m, NCH2); 6.95 (1H, t, J = 7.5, C6H5); 7.29 (2H, t, J = 7.6, C6H5); 7.38-7.51 (5H, m,
C6H5); 7.72 (2H, d, J = 8.4, C6H5); 11.08 (1H, s, NH). Mass spectrum, m/z (Irel, %): 309 [M-C3H3Br]+ (18).
Found, %: C 58.81; H 4.98; N 9.50. C21H22BrN3S. Calculated, %: C 58.88; H 5.14; N 9.81.
Intramolecular Cyclization of 1-[1-Alkylsulfanyl-2-phenyl-2-(phenylhydrazono)ethylidene]pyrrolidi-
nium Bromides 3a-c (General Method). The Cs2CO3 (0.15 g, 0.47 mmol) was added to a solution of pyrrolidinium
salt 3a-c (0.47 mmol) in DMF (5 ml). The reaction mixture was stirred until the starting reagent disappeared as
indicated by thin-layer chromatography. The solvent was evaporated in vacuum. Pyrrolotriazine 4 was separated on
a column packed with KSK silica gel (40-100 m) using 4:1 hexane–ethyl acetate as the eluent.
1,3-Diphenyl-6,7,8,8a-tetrahydro-1H-pyrrolo[2,1-c]-1,2,4-triazine-4-thione (4), mp 110-111°C.
1H NMR spectrum, , ppm (J, Hz): 1.94-2.17 (3H, m, CH2); 2.61-2.70 (1H, m, CH2); 3.80-3.98 (2H, m, CH2);
5.10 (1H, dd, J = 5.8, J = 7.6, H-8a); 7.25-7.38 (4H, m, C6H5); 7.39-7.47 (4H, m, C6H5); 7.65 (1H, dd, J = 8.0,
J = 2.0, C6H5). 13C NMR spectrum, , ppm: 21.0 (CH2), 32.1 (CH2), 51.5 (CH2), 71.7 (C(8a)H), 123.2, 126.1,
127.3, 127.9, 128.8, 129.0, 135.3, 144.3, 145.6, 175.8 (CS). Mass spectrum, m/z (Irel, %): 307 [M]+ (2). Found,
%: C 70.12; H 5.29; N 10.59. C18H17N3S. Calculated, %: C 70.33; H 5.57; N 10.43.
This work was carried out with the financial support of the Russian Basic Research Fund
(Grants 08-03-00376_a, 08-03-92208 GFEN (Natural Sciences State Fund)_a, 10-03-96084-r-ural_a).
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