Synthesis of 13-phenyl-9,15-dithia-2-azatricyclo-[9.3.1.0 3,8]pentadeca-1(14),3,5,7-tetraene

Full text of DOI:10.1007/s10593-011-0875-0

Chemistry of Heterocyclic Compounds, Vol. 47, No. 8, November, 2011 (Russian Original Vol. 47, No. 8, August, 2011)
SYNTHESIS OF 13-PHENYL-9,15-DITHIA-2-AZATRICYCLO-
[9.3.1.03,8]PENTADECA-1(14),3,5,7-TETRAENE*
N. T. Pokhodylo1, M. D. Obushak1**, and V. S. Matiychuk1
Keywords: 9,15-dithia-2-azatricyclo[9.3.1.03,8]pentadeca-1(14),3,5,7-tetraene, domino reactions, hetero
Diels-Alder reaction.
Domino reaction methodology has found increasing use in recent times for organic synthesis [1, 2]. In
particular, domino reactions in which an initially formed heterodiene fragment takes part in subsequent
cycloaddition reactions [1-4] are of particular interest.
In this work we have studied the potential formation of a novel heterocyclic system via an intramolecular
hetero Diels-Alder type reaction of the initially formed product from the N-acylation of the 2-(2-propen-
1-ylsulfanyl)aniline (1).
O
O
NH
2`
H2N
Et3N
Cl
6`
4`
S
+
MeCN
1
5
3
S
2
3
1
P2S5
Dioxane
S
S
S
10
11
9
7
NH
15S
O
5
2
N
H
1
13
N
H
S
1' 3'
5'
14
6
4
5
Reaction of the amine 1 with cinnamoyl chloride (2) gave compound 3 which has a C=C–C=O heterodiene
system [5]. It was found that an intramolecular hetero Diels-Alder reaction to give compound 4 does not occur,
even upon refluxing in toluene and with Lewis acid catalysts. It is known that ,-unsaturated
_______
*Dedicated to the memory of Academician M. O. Lozinskii.
**To whom correspondence should be addressed, e-mail: obushak@in.lviv.ua.
1Ivan Franko National University of Lviv, 6 Kyryla and Mefodia St., Lviv 79005, Ukraine, e-mail:
obushak@in.lviv.ua.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1274-1276, August, 2011.
Original article submitted May 15, 2011.
0009-3122/11/4708-1053©2011 Springer Science+Business Media, Inc.
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thiocarbonyl fragments serving as dienes are convenient "building blocks" for the preparation of sulfur-
containing six-membered heterocycles [3, 4]. Hence, it was of interest to prepare the thioamide analog of
compound 3 and to study its possible participation in a cycloaddition reaction.
By carrying out a thionylation of compound 3 with P2S5 in dioxane, we prepared the 13-phenyl-9,15-di-
thia-2-azatricyclo[9.3.1.03,8]pentadeca-1(14),3,5,7-tetraene (6) which is a novel heterocyclic system containing
thiopyran and dithiazocine rings. Formation of compound 6 evidently occurs via an intramolecular cycloaddition
reaction of the intermediately formed compound 5.
Hence, the scheme, we proposed for the conversion of the phenylpropeneamide 3 to the tricyclic
compound 6, makes an intramolecular thia type Diels-Alder reaction an attractive route to the synthesis of
3,4-dihydro-2H-thiopyrans condensed to eight-membered rings.
1H NMR spectra were recorded on a Varian Mercury 400 MHz instrument for DMSO-d6 solutions with
TMS as internal standard. Mass spectra were obtained on an Agilent 1100 LC/MSD chromato-mass
spectrometer with a Zorbax SB-C18 1.8  column using atmospheric pressure chemical ionization (APCI).
(2E)-3-Phenyl-N-[2-(2-propen-1-ylsulfanyl)phenyl]-2-propeneamide (3). Cinnamoyl chloride (2)
(0.83 g, 5 mmol) was added with vigorous stirring to a solution of 2-(2-propen-1-ylsulfanyl)aniline (1) (0.82 g,
5 mmol) and Et3N (0.7 ml, 5 mmol) in MeCN (5 ml). The product was heated to reflux, cooled to room
temperature, and stirred to the formation of a precipitate. The precipitate was filtered off and purified by
recrystallization from methanol. Yield 1.35 g (92%); mp 93-94ºC (mp 99-100ºC (EtOAc–hexane) [5]). 1H NMR
spectrum, , ppm (J, Hz): 3.59 (2H, d, J = 6.8, CH2); 5.03 (1H, d, J = 10.0) and 5.11 (1H, d, J = 16.9, =CH2);
5.78-5.88 (1H, m, CH=); 7.10 (1H, d, J = 15.5, CH=); 7.18 (1H, t, J = 7.2, H-4); 7.25-7.29 (1H, m, H-5);
7.40-7.50 (4H, m, H-6 + H-3',4',5'); 7.60 (1H, d, J = 15.7, CH=); 7.67 (2H, d, J = 7.1, H-2',6'); 7.76 (1H, d,
J = 7.5, H-3); 9.50 (1H, s, NH). Mass spectrum, m/z: 296 [M+H]+. Found, %: C 73.01; H 5.99; N 4.58.
C18H17NOS. Calculated, %: C 73.19; H 5.80; N 4.74.
13-Phenyl-9,15-dithia-2-azatricyclo[9.3.1.03,8]pentadeca-1(14),3,5,7-tetraene (6). Compound
3
(1.47 g, 5 mmol) was dissolved with heating in dry dioxane (10 ml) and P2S5 (0.6 g, 2.6 mmol) was added. The
reaction mixture was refluxed for 72 h, cooled to room temperature, filtered through alumina, and the filtrate
was poured into a beaker with ice. The precipitate formed was filtered off, washed with water, and recrystallized
from aqueous ethanol. If the product formed a viscous liquid it was extracted with hot hexane and the extract
was evaporated at room temperature. Yield 0.88 g (57%); mp 88-89ºC. 1H NMR spectrum, , ppm (J, Hz): 3.49
3
3
(2H, d, J13,3a = 7.0, H-13a,b); 5.04-4.98 (2H, m, H-2a,2b); 5.78-5.89 (1H, m, H-3); 7.05 (1H, d, J14,15 = 15.6,
H-14); 7.10 (1H, dd, J = 7.6 and J = 1.0, H-12); 7.24-7.29 (2H, m, H-10,11); 7.36-7.45 (3H, m, H-3',4',5'); 7.57
3
(1H, d, J15,14 = 15.6, H-15); 7.62 (2H, d, J = 7.0, H-2',6'); 7.97 (1H, d, J = 8.0, H-9); 9.24 (1H, s, NH). Mass
spectrum, m/z: 312 [M+H]+. Found, %: C 69.20; H 5.58; N 4.37. C18H17NS2. Calculated, %: C 69.41; H 5.50;
N 4.50.
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