Crystal Structure of 3-(4-Methoxy-benzylidene)-isothiochroman-4-one

Article abstract of DOI:10.1007/s10870-009-9628-7

The title compound, 3-(4-methoxy-benzylidene)-isothiochroman-4-one (C ₁₇H₁₄O₂S) was prepared from the reaction of isothiochroman-4-one with benzaldehyde in the presence of small amount of HCl. The structure of the synthesised compound was determined by IR, ¹H NMR and X-ray crystallography. The structure was solved in monoclinic, space group P2₁/n with a = 3.9773 (7) A, b = 10.918 (2) A, c = 30.609 (6) A, β = 90.615 (3)°, V = 1329.1 (4) A³, Z = 4 and with R _int = 0.047. The bicyclic ring of isothiochroman-4-one moiety does not adopt a planar geometry. The molecular conformation is stable via C10-H???O1 and C16- H???S1 intramolecular hydrogen-bonding interactions. These contacts involve molecules in an extended two-dimensional sheet to the bc plane.

Full text of DOI:10.1007/s10870-009-9628-7

J Chem Crystallogr (2010) 40:165–168
DOI 10.1007/s10870-009-9628-7
ORIGINAL PAPER
Crystal Structure of 3-(4-Methoxy-benzylidene)-isothiochroman-
4-one
¨
M. Akkurt Æ S. O. Yıldırım Æ A. Kerbal Æ B. Bennani Æ
T. Ben Hadda Æ Z. H. Chohan Æ Vickie McKee
Received: 8 May 2009 / Accepted: 29 August 2009 / Published online: 22 September 2009
Ó Springer Science+Business Media, LLC 2009
Abstract The title compound, 3-(4-methoxy-benzyli-
dene)-isothiochroman-4-one (C17H14O2S) was prepared
from the reaction of isothiochroman-4-one with benzalde-
hyde in the presence of small amount of HCl. The structure
Keywords Crystal structure ꢀ
3-(4-Methoxy-benzylidene)-isothiochroman-4-one ꢀ
Benzaldehyde ꢀ Isothiochroman-4-one
1
of the synthesised compound was determined by IR, H
NMR and X-ray crystallography. The structure was solved
˚
in monoclinic, space group P21/n with a = 3.9773 (7) A,
Introduction
˚
˚
b = 10.918 (2) A, c = 30.609 (6) A, b = 90.615 (3)°,
Spiro-heterocyclic compounds containing one or two func-
tionalised arms at various positions have emerged as
potentially interesting drugs owing to their patented selec-
tive antitumoral behaviour against breast-cancer (MCF7-
strains) [1], antitubercular agents [2] or anti-HIV agents [3].
These studies showed that spiro-heterocyclic compounds
bearing an oxygen or sulfur heteroatom in the 3-position/
C=O are highly active not only as anti-tubercular or
anti-HIV agents but as potential combined antitubercular/
anti-HIV agents [4]. From the general structure–activity
relationship, it appears that functionalized side chain(s)
characterised by pendant sites such as (O=C–Y–Z), where
Y–Z is N=N or O–N, are crucial for bioactivity. The
incorporated heteroatom centres S or O on 3-position seem
to have critical interactions with the bacterial cell receptors
or may be as centre donors in metal complexation. The
isothiochroman-4-one, was prepared since a long time [5]
3
V = 1329.1 (4) A , Z = 4 and with Rint = 0.047. The
˚
bicyclic ring of isothiochroman-4-one moiety does not
adopt a planar geometry. The molecular conformation is
stable via C10–HꢀꢀꢀO1 and C16–HꢀꢀꢀS1 intramolecular
hydrogen-bonding interactions. These contacts involve
molecules in an extended two-dimensional sheet to the bc
plane.
¨
M. Akkurt (&) ꢀ S. O. Yıldırım
Department of Physics, F.A.S., Erciyes University,
38039 Kayseri, Turkey
e-mail: akkurt@erciyes.edu.tr
A. Kerbal ꢀ B. Bennani
Laboratoire de Chimie Organique,
´
Faculte des Sciences Dhar El Mehraz, Fes, Morocco
¨
by cyclising the chloride 4-phenyl-3-thiabutanoıc acid in
nitrobenzene in presence of tri-chloride aluminium. The
T. B. Hadda
Laboratoire de Chimie des Materiaux,
´
Universite Mohammed Premier, Oujda, Morocco
¨
chloride 4-phenyl-3-thiabutanoıc acid has been cyclised
´
by addition of trichloride aluminium in a mixture of
(chloroforme/disulfure-carbone). A group of researcher [6]
has improved its yield by cyclising the 4-phenyl-3-thiabut-
Z. H. Chohan (&)
Department of Chemistry, Bahauddin Zakariya University,
¨
anoıc acid (3) by addition of phosphoric anhydride [P2O5] on
‘‘Hyflosupercelle’’ in benzene. After this period, another
Multan, Pakistan
e-mail: dr.zahidchohan@gmail.com
¨
group [7] has cyclised this chloride 4-phenyl-3-thiabutanoıc
V. McKee
Department of Chemistry, Loughborough University,
Leicestershire LE11 3TU, UK
acid by using the stannic chloride (SnCl4) as catalysor in the
disulfure of carbone. In addition the synthesis of the titled
123

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J Chem Crystallogr (2010) 40:165–168
compound containing the sulphur atom at position 3 has
been undertaken. In this connection, we recently investi-
gated the synthesis and optimisation of starting expensive
precursors of these spiro-heterocycles [8]. In a continuation
of our investigations of the precursors synthesis, we describe
here the synthesis and structure of 3-(4-methoxy-benzyli-
dene)-isothiochroman-4-one (6), the principal precursor of
our spiro-anti-HIV drugs.
Fig. 1 The molecular structure of (6) with the atom-numbering
scheme and 50% probability displacement ellipsoids. H atoms have
been saved for C8=O1ꢀꢀꢀH10 and C16–H16ꢀꢀꢀS1 possible intramolec-
ular interactions
Results and Discussion
Chemistry
The general protocol of the compound, isothiochroman-
4-one (5) analogues synthesis consists to realise the
intramolecular reaction of Perkin on (o-carboxy)-benzyl-
oxyacetic ester or intramolecular reaction of Dieckmann
on substituted (o-carboxy)-benzyloxythiacetic acid or
(o-methoxycarbonyl-ester or o-ethoxycarbonyl)-benzyloxy-
acetic ester or (o-methoxycarbonyl or o-ethoxycarbonyl)-
benzylyhioacetic esters, followed by a decarboxylation [9,
10] as described in (Scheme 1).
Crystal Structure
The molecular structure of (6) (Fig. 1, Table 1) shows the
expected bond lengths and angles [11]. The thiopyran-3-
one ring of the isothiochroman-4-one unit are far away to
be perfectly planarity [the puckering parameters are
˚
QT = 0.620(3) A, h = 177.6 (4)° and u = 93 (8)° [12].
The functionalised groups (C8=O1 and S1–C9) adopts a Z-
configuration around double bond C9=C10 and O1–C8.
On the other hand C9=C10 double bonds are in a non
common plane with a torsion angle (O1=C8–C9=C10) of
The titled compound, 3-(4-methoxy-benzylidene)-iso-
thiochroman-4-one (6) has synthesised through number of
intermediate reactions. Benzyl chloride reacted with
sodium salt of ethyl-thioglycolate (NaS-CH2-CO2Et) in the
presence of ethanol–water solution (50:50) to produce
acetic acid of 4-phenyl-3-thiabutanoate of ethyl-ester (2).
˚
13.3(4) A, while the C9–C10–C11–C16 torsion angle is
-8.1 (5)°.
The sulfure atom adopts a cisoidal conformation with
H–C16 atom (Fig. 1). The dihedral angle between the C7/
C2/C1 and C1/S1/C9 planes is calculated as 52.63° (24) by
using the PARST program [13], while the dihedral angle
between the two benzene rings (C2–C7) and (C11–C16) is
34.68 (14)°. In the structure, there is no classic hydrogen
bonds, but only weak C10–HꢀꢀꢀO1 and C16–HꢀꢀꢀS1 intra-
molecular interactions, as detailed in Table 2. These con-
tacts involve molecules in an extended two-dimensional
sheet parallel to the bc plane (Fig. 2).
¨
The 4-phenyl-3-thiabutanoıc acid (3) was obtained by
hydrolysis of 4-phenyl-3-thiabutanoate of ethyl-ester (2) in
a mixture of concentrated hydrochloric acid and acetic
¨
acid. Similarly, 4-phenyl-3-thiabutanoıc acid (4) was
obtained by the reaction of compound (3) with SOCl2.
¨
Further, 4-phenyl-3-thiabutanoıc acid (4) reacted with tol-
uene in presence of aluminium chloride [6, 7] to give
isothiochroman-4-one (5) which on reacted with aromatic
aldehyde to give title compound (6).
Scheme 1 General protocol
leading to isothiochroman-
4-ones and analogues
(X = O,S)
O
CO2R
CO2R
NaH / D.M.S.O
ou Na / Toluène
NaOH / EtOH
X
X
CO2R
R1
R1
O
X = O, S
R1 = H
R = Me, Et
X = O, S ; R1 = H
X = S ; R1 = Me
X
R1
OAc
CO2R
CH3CO2K
KOH / EtOH
(CH3CO)2O
X
CO2R
X
R1
R1
X = O, S ; R1 = H
X = S ; R1 = Me
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J Chem Crystallogr (2010) 40:165–168
167
Fig. 2 View of the packing
diagram of compound (6)
in the unitcell
˚
Table 2 Selected geometric parameters (A, °)
Table 1 Crystal data and refinement information
S1–C1
1.811 (3)
1.759 (3)
1.225 (4)
1.368 (4)
1.438 (4)
1.402 (5)
C7–C8
1.497 (4)
1.493 (4)
1.355 (4)
1.464 (4)
1.400 (4)
Crystal data
S1–C9
C8–C9
C
17H14O2S
Z = 4
Mr = 282.35
Dx = 1.411 Mg m-3
Mo Ka radiation
Cell parameters from 2,891 reflections
h = 2.3–25.7°
l = 0.24 mm-1
T = 150 (2) K
O1–C8
C9–C10
C10–C11
C11–C16
O2–C14
Monoclinic, P21/n
˚
a = 3.9773 (7) A
O2–C17
˚
b = 10.918 (2) A
C2–C7
˚
C1–S1–C9
C14–O2–C17
S1–C1–C2
C1–C2–C3
C1–C2–C7
O1–C8–C7
O1–C8–C9
O2–C14–C15
C9–S1–C1–C2
C1–S1–C9–C8
C1–S1–C9–C10
99.85 (15) C7–C8–C9
119.3 (3)
119.1 (2)
123.4 (2)
117.3 (3)
131.6 (3)
126.0 (3)
115.8 (3)
c = 30.609 (6) A
116.7 (2)
111.3 (2)
121.5 (3)
119.7 (3)
119.8 (3)
120.8 (3)
124.8 (3)
-55.4 (2)
28.2 (3)
S1–C9–C8
b = 90.615 (3)°
V = 1329.1 (4) A
3
˚
S1–C9–C10
C8–C9–C10
C9–C10–C11
C10–C11–C16
O2–C14–C13
Lath, yellow
Data collection
Bruker APEX-II CCD
diffractomer
2,643 reflections with I [ 2r(I)
u and x scans
Rint = 0.047
hmax = 28.4°
Absorption correction:
none
C2–C7–C8–O1
C2–C7–C8–C9
C6–C7–C8–O1
C6–C7–C8–C9
O1–C8–C9–S1
O1–C8–C9–C10
C7–C8–C9–S1
C7–C8–C9–C10
S1–C9–C10–C11
C9–C10–C11–C16
O2–C14–C15–C16
151.8 (3)
-30.8 (4)
-27.8 (4)
149.6 (3)
-172.0 (2)
13.3 (4)
12,832 measured reflections h = -5 ? 5
3,224 independent
reflections
k = -14 ? 14
l = -40 ? 40
-157.5 (3)
C17–O2–C14–C13 -179.8 (3)
Refinement
Refinement on F2
R[F2 [ 2r(F2)] = 0.071
C17–O2–C14–C15
S1–C1–C2–C3
S1–C1–C2–C7
C1–C2–C3–C4
C1–C2–C7–C8
C8–C9–C10–C11
0.5 (4)
-135.0 (3)
46.7 (3)
H atoms constrained to parent site
Calculated weights
w = 1/[r2(F2o) ? (0.0795P)2 ?
2.2377P] where P = (F2o ? 2Fc2)/3
10.7 (4)
-178.3 (3)
-1.0 (4)
-164.0 (3)
0.7 (5)
wR(F2) = 0.176
S = 1.02
(D/r)max \ 0.0001
-1
˚
175.1 (3)
-8.1 (5)
177.2 (3)
Dqmax = 0.77 eA
-1
˚
C12–C13–C14–O2 -177.4 (3)
3,224 reflections
182 parameters
Dqmin = -0.33 eA
˚
Extinction correction: none
Hydrogen-bond parameters (A, °)
D–HꢀꢀꢀA
D–H
HꢀꢀꢀA
DꢀꢀꢀA
D–HꢀꢀꢀA
C10–H10ꢀꢀꢀO1
C16–H16ꢀꢀꢀS1
0.93
0.93
2.35
2.47
2.758(4)
3.165 (3)
106
131
Experimental
Synthesis of 3-(4-Methoxy-benzylidene)-isothiochroman-
4-one (6)
stirred at room temperature for 24 h. A white precipitates
were formed. It was filtered and then purified by simple
crystallisation in ethanol. The desired compound (6) was
separated from ethanol as analytically pure uncoloured
crystals (Scheme 2).
To a mixture of isothiochroman-4-one (5) (40 mmol) and
benzaldehyde (40 mmol) were added in little portions
15 mL of chlorohydric acid (HCl) and then the solution is
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J Chem Crystallogr (2010) 40:165–168
Scheme 2 Synthesis of
3-(4-methoxy-benzylidene)-
isothiochroman-4-one (6)
NaS-CH2-CO2Et
HCl/CH3CO2H
(50/50)
O
O
S
S
H
S
Cl
S
EtOH/H2O (50/50)
O
O
2
3
1
SOCl2
O
O
H
O
H
O
O
AlCl3
S
Cl
O
4
5
6
Transparent crystals. Yield 87%. M.p. = 93–95 °C. IR
(nujol, m cm-1): 1,647 (C=O), 1,570 (C=C). 1H NMR
(300 MHz, CDCl3) d ppm: 8.1 (s, 1H, C10–H), 6.1–8.0 (m,
8H, 2 Ph), 3.9 (s, 2H, SCH2), 3.8 (s, 3H, OCH3).
The 4-phenyl-3-thiabutanoate-ethyle (2), 4-phenyl-3-
thiabutanoic acid (3), chloride 4-phenyl-3-thiabutanoic
acid (4) and isothiochroman-4-one (5) have been prepared
as described in literature.
Data collection: APEX2 [14]. Cell refinement: APEX2.
Data reduction: SAINT. Program(s) used to solve structure:
SIR97 [15]. Program(s) used to refine structure: SHEL-
XL97 [16]. Molecular graphics: ORTEP-3 for Windows
[17]. Software used to prepare material for publication:
WinGX [18].
Acknowledgments This work was supported by the Program du
Projet Global de Recherche de l’Universite0 Mohamed Premier
d’Oujda ‘PGR-BH-20050 and PARS CO4 Grants from the Ministry
of National Education of Morocco.
4-Phenyl-3-Thiabutanoate Ethyle (2)
Yield = 85%. Eb = 114 °C. IR (nujol) m(cm-1): 1,720
(C=O). 1H NMR (CDCl3) d (ppm): 1.23 (t, 3H, CH3–CH2,
J = 7 Hz); 3.02 (s, 2H, 2H2); 3.80 (s, 2H, 2H4); 4.10 (q,
2H, CH3–CH2, J = 7 Hz); 7.25 (m, 5H, ph).
References
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4-Phenyl-3-Thiabutanoic Acid (3)
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3. Bennani B, Kerbal A, Larbi NB, Hadda TB (2004) Synthesis and
application of some spiro-isoxazolines as new anti-HIV agents.
Moroccan Patent, Casablanca, N 2770
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5H, Ph).
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¨
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1(4):410–418
Yield = 80%. Eb = 125 °C. IR (nujol) m(cm-1): 1,790
1
(C=O). H NMR (CDCl3) d(ppm): 3.45 (s, 2H, 2H2); 3.75
(s, 2H, 2H4); 7.25 (m, 5H, Ph).
Isothiochroman-4-One (5)
11. Allen FH (2002) Acta Cryst B58:380–388
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J Appl Cryst 32:115–119
White crystals. Yield = 50% . Eb = 138 °C. F = 60 °C.
1
IR (KBr): m(cm-1): 1,670 (C=O). H NMR (CDCl3): 3.55
(s, 2H, 2H3); 3.95 (s, 2H, 2 H1); 7.15–7.55 (m, 3H, Ph);
8.10 (m, 1H).
H atoms were geometrically located in calculated posi-
tions and treated as riding on their parent atoms, with
˚
C–H = 0.93–0.97 A, and with Uiso(H) = 1.2Ueq(C) and
16. Sheldrick GM (2008) Acta Cryst 64:112–122
17. Farrugia LJ (1997) J Appl Cryst 30:565
18. Farrugia LJ (1999) J Appl Cryst 32:837–838
U
iso(H) = 1.5Ueq(C) for methyl group.
123