Non-catalytic approach to the synthesis of partially reduced 'S' shaped dioxathia- and oxadithiahelicenes through base induced inter- and intramolecular C-C bond formation

Article abstract of DOI:10.1039/c1ob06091k

An efficient and convenient route for the construction of helical 'S' shaped dioxathia- and oxadithiahelicenes with oxygen and sulfur atoms located in the middle of the outer helix has been developed through base induced inter- and intramolecular C-C bond

Full text of DOI:10.1039/c1ob06091k

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PAPER
Non-catalytic approach to the synthesis of partially reduced ‘S’ shaped
dioxathia- and oxadithiahelicenes through base induced inter- and
intramolecular C–C bond formation†
Hardesh K. Maurya,a Vishnu K. Tandon,*a Brijesh Kumar,b Abhinav Kumar,a Volker Huchc and
Vishnu Ji Ram*a
Received 6th July 2011, Accepted 18th August 2011
DOI: 10.1039/c1ob06091k
An efficient and convenient route for the construction of helical ‘S’ shaped dioxathia- and
oxadithiahelicenes with oxygen and sulfur atoms located in the middle of the outer helix has been
developed through base induced inter- and intramolecular C–C bond formation from the reaction of
4-sec-amino-2-oxo-2,5-dihydrothiochromeno[4,3-b]pyran-3-carbonitriles with 3,4-dihydro-2H-
benzo[b]oxepin-5(2H)-ones, 3,4-dihydrobenzo[b]thiepin-5(2H)-one and thiochroman-4-ones separately.
Quantum chemical calculations have also been carried out to explore the geometries and electronic
structures of newly synthesized compounds to envisage the pathway for interconversion of both
atropisomers. The determination of helicity parameters and configurational stability demonstrate that
the energy barrier is strongly dependent on the nature of hetero-atoms present.
such as bond lengths, dihedral angles and configurational stability.
Thus, [4]carbohelicenes are quite stable at room temperature even
Introduction
Helicenes are three-dimensional polycyclic, thermally stable p
conjugated ortho-annulated aromatic ring systems with inherent
chirality. The unique physical and chemical properties of these
non-planar helical molecules urged continued interest in the
fascinating field of helicene chemistry.1 Besides, optical2 and
electronic3 properties, the inherent chirality4 of helicenes has led to
their promising applications in asymmetric catalysis,5 asymmetric
molecular recognition,6 liquid crystals,7 dyes,8,9 sensors,8,9 electro-
static switches,10 polymer synthesis7,11,12 and circularly-polarized
luminescent devices.7,11,12 The determination of racemisation bar-
rier (RB) reflects the repulsive interaction between terminal
rings and is a crucial indicator of helicity. The RBs in case of
carbohelicenes, depend upon several factors such as the number
of ortho-annulated aromatic rings and substituents present at helix
sites and the modulation of steric hindrance on the terminal
positions of the inner helix.8,13 Partial reduction in the molecule
also modulates the racemisation barrier. In fact, the nature and
position of heteroatoms also influence the helicity parameters
with the introduction of a bulky substituent on the terminal rings
of the inner helix.9,14 The introduction of methyl substituent at
position 1 increases configurational stability similar to the effect
of an additional aromatic ring.
An overview of literature over the last century has high-
lighted carbohelicenes as helical frameworks. Helicenes have
classically been synthesized by oxidative photocyclization of
bis(stilbenes)10b,15 with poor regio-control. The requirement of
highly substituted helicenes for various applications has led to
the development of several novel approaches to their syntheses.
Katz et al.16,17 have described an access to the synthesis of
helical bisquinones through Diels–Alder reaction. The transition-
metal catalyzed [2 + 2 + 2]cycloisomerization of triynes and
dienetriynes,16,17 was found as alternative routes to the synthesis
of this class of compounds. In 2006, Collins et al. published
a new synthetic route to highly substituted helicenes with
different frameworks by ring closing olefin metathesis.18,19 An
intramolecular Pd-catalyzed C–C bond formation20 and Friedel–
Crafts cyclization strategies21 have also been followed for the
construction of helicenes of different structural frameworks.
Recently, heterohelicenes4,22 (i.e. oxa, aza, thia, oxathia) have
emerged as extremely attractive molecules because of their
photorefractive properties.23 Karikomi et al.24 have developed
stereoselective synthesis of [5]helicenes by oxy-Cope rearrange-
ment as key step. Recently, Genetet et al.25 have reported an
elegant enantioselective synthesis of helicenes through chirality
transfer from an enantiopure tether to a flexible [5]helicene
backbone.
aDepartment of Chemistry, Lucknow University, Lucknow, 226 007, India.
E-mail: vjiram@yahoo.com; Tel: +91 522 2960779
bDivision of SAIF, Central Drug Research Institute, Lucknow, 226001, India
cInstitute of Inorganic Chemistry, University of Saarland, Saarbrucken,
Germany
† Electronic supplementary information (ESI) available: Optimized struc-
tures along with the Cartesian coordinates (4f.xyz, 4fTS.xyz, 9c.xyz,
9cTs.xyz, 9d.xyz, 9dts.xyz) and copies of IR, HRMS, 1H NMR, 13C NMR
spectra of compounds. CCDC reference numbers 831578 (4f), 831579
(9c) and 831577 (9d). For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c1ob06091k
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The synthesis of regio-defined heterohelicenes is of significant
interest.4,18 Regardless of recent significant progress in helicene
chemistry, development of new, short, efficient routes are still
desired to allow further functionalization to build additional rings.
Results and discussion
The fascinating architecture of helicenes and their vivid unex-
plored potential applications in material science stimulated us
to devise an economical, efficient and short synthesis through
base induced inter- and intramolecular C–C bond formation
from the reaction of suitably functionalized 4-sec-amino-2-oxo-
2,5-dihydrothiochromeno[3,4-c]pyran-3-carbonitriles (4) with 3,4-
dihydro-2H-benzo[b]oxepin/thiepin-5(2H)-ones29 (5), a feasible
concept exhibiting a high degree of synthetic flexibility for the con-
struction of partially reduced dioxathia- and oxadithahelicenes,
not reported so far. The crux of methodology lies in non-catalytic
synthesis of various partially reduced dioxthia- and oxadithia-
helicenes, endowed with halo, amino and nitrile functionalities,
transformable to other groups either catalytically or chemically.
Besides this, the methodology also provides an avenue for the
synthesis of partially reduced helicenes, not easily obtainable either
chemically or catalytic regioselective hydrogenation.
Scheme 1 Synthesis of 4-sec-amino-2-oxo-2,5-dihydrothiochromeno-
[4,3-b]pyran-3-carbonitriles (4).
It has been reported26 that the planarity of the rings in
polycyclic systems induces carcinogenicity which is either reduced
or destroyed by distortion in the planarity of the rings. The partial
reduction is also one of the ways for disrupting the planarity of
rings. Thus, we developed an elegant synthetic route to induce
distortion in the planarity of the rings through partial reduction,
employing partially reduced precursors.
As apparent from the structure of 4-methylthio-2-oxo-2,5-
dihydrothiochromeno[4,3-b]pyran-3-carbonitriles (3a,b), these
were obtained from the reaction of thiochroman-4-ones (2) and
methyl 2-cyano-3,3-dimethylthioacrylate27 (1). Amination28 of 3
with sec-amine in boiling ethanol resulted in 4-sec-amino-2-
oxo-2,5-dihydrothiochromeno[4,3-b]pyran-3-carbonitriles (4) and
were used as precursors for the ring transformation reactions
(Scheme 1).
The synthetic potential of 4-sec-amino-2-oxo-2,5-dihydro-
thiochromeno[4,3-b]pyran-3-carbonitriles (4) is enormous. The
unique structural features and the presence of functional groups
were exploited for the construction of a variety of heteroarenes of
helical shape.
It is evident from the topography of the thiochromeno[4,3-
b]pyran-3-carbonitriles 3 and 4 that the positions C2, C4 and C10b
are electron deficient, in which the latter is particularly so, and
prone to nucleophilic attack because of an extended conjugation
and the presence of an electron-withdrawing CN substituent at
position 3 of the lactones 3, 4. Both the lactones (3, 4) are very
useful synthons for the ring transformation reactions. The basic
difference in both the lactones lies in the nature of substituent
present at position 4. In the case of lactone 3 the –SCH3 substituent
at position 4 is more labile and highly vulnerable to nucleophilic
attack compared to the sec-amino substituent in 4.
Scheme 2
unfortunately only one compound was isolated and characterized.
Nevertheless, the reaction initiated with attack of nucleophile at
position 4 rather than at C10b, followed by ring closure involving
cyano function to yield 8. The only option to obtain the desired
product 6 was to reduce the electrophilicity of the C-4 position
by replacing –SCH3 by a sec-amino substituent to facilitate the
attack of carbanion at C-10b.
Thus, an equimolar mixture of the 4-sec-amino-2-oxo-
2,5-dihydrothiochromeno[4,3-b]pyran-3-carbonitriles (4), 3,4-
dihydro-2H-benzo[b]oxepin/thiepin-5(2H)-ones29 (5) and powde-
red NaOH as a base was stirred for 14 h in DMSO with continuous
monitoring of the reaction progress by TLC. The usual workup
and purification on Si gel column chromatography exclusively
However, the reaction of an equimolar mixture of 4-methylthio-
2-oxo-2,5-dihydrothiochromeno[4,3-b]pyran-3-carbonitriles (3)
and 3,4-dihydro-2H-benzoxapin-5-one (5) did not deliver the
expected products 6 and 7 (Scheme 2) but in lieu produced 8. We
performed several reactions to make more derivatives of 8 but
gave
(Z)-2-(1,2-dihydro-10H-thiochromeno[3,4-c]pyrano[3,2-
d]benzo[b]oxepine(2H)-ylidene)acetonitriles (9), following path B,
without formation of another expected product 9-sec-amino-1,2-
dihydro-10H-thiochromeno[4,3-e]dibenzo[b,d]oxepine-9-carbo-
nitriles (10) through path A, as depicted in Scheme 3.
606 | Org. Biomol. Chem., 2012, 10, 605–613
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formation of 4-(4-methylpiperazin-1-yl)-2-oxo-5,6-dihydro-2H-
benzo[h]chromene-3-carbonitrile (4j) by thiochroman-4-ones (2)
gave products 11b–c, analogous to 9a as shown in Scheme 4.
Scheme
4
2-(7,8-Dihydrobenzo[f ]thiochromeno[4,3-c]isochromen-6-
(13H)-ylidene)acetonitriles 11a–c.
Crystal structures and quantum chemical studies
Crystals of X-ray quality for 4f, 9c and 9d were obtained by
slow evaporation of the solvent (dichloromethane–hexane) at
room temperature. The molecular structures of the compounds
with arbitrary numbering are presented in Fig. 1, illustrating the
non-planar, helically distorted conformation of the molecules.
Compound 4f crystallizes in the Pca21 space group with eight
molecules in the orthorhombic unit cell. The least-square plane
calculations reveal that only ring A is planar, while the other rings
B and C are non-planar. The non-planarity of the six membered
ring B is attributed to the presence of sp3 hybridized C12 and S1
atoms. In the case of the ring C, the deviation from planarity is
because of the presence of one sp3 hybridized oxygen atom O1.
The deviations of S1 and C12 from the plane of ring B are -0.159
Scheme
3 A plausible mechanism for the synthesis of the (Z)-
2-(1,2-dihydro-10H-thiochromeno[3,4-c]pyrano[3,2-d]benzo[b]oxepin-
(2H)-ylidene)acetonitriles (9) and 9-sec-amino-1,2-dihydro-10H-thiochro-
meno[4,3-e]dibenzo[b,d]oxepine-9-carbonitriles (10).
˚
and +0.694 A, respectively, whereas the oxygen atom O1 deviates
˚
by -0.178 A from the plane of the ring C. The torsion angles C5–
In order to study the effect of the 4-sec-amino substituent
in 4 on the yield of the dioxathia- (9a–c) and dithia- oxahe-
licenes (9d,e), 4-pyrrolidin-1-yl-, morpholin-4-yl-, piperidin-1-yl-
and (4-arylpiperazin-1-yl)-2-oxo-2,5-dihydrothiochromeno[4,3-
b]-3-carbonitriles were used as precursors (Table 1). However,
only 4-(morpholin-4-yl)-2,5-dihydrothiochromeno[4,3-b]pyran-3-
carbonitriles (4d) with thiochroman-4-ones (2) gave ex-
clusively (Z)-2-(1,2-dihydro-10H-thiochromeno[3,4-c]pyrano[3,2-
d]benzo[b]oxepine(2H)-ylidene)acetonitriles (9) as evidenced from
the single-crystal X-ray diffraction study of 9c.
To generalize the reaction, the ring transformation of 9-chloro-
2-oxo-4-(4-phenylpiperazin-1-yl)-2,5-dihydrothiochromeno[4,3-
b]pyran-3-carbonitrile (4g) with 6-chlorothiochroman-4-one
(2b) was carried out which gave product 11a under
analogous reaction conditions. Similarly, the ring trans-
C6–C7–O1 and C6–C7–O1–C8 are 16.21 and 171.73◦ respectively.
Compounds 9c and 9d crystallized in P21/n and P21/c
space groups, respectively, with four and eight molecules in the
monoclinic unit cells, respectively. In both the compounds, the
least-square plane calculation from X-ray crystallographic data
indicates that the fully unsaturated rings A, C and E are nearly
planar. The rings B adopt half chair conformation because of the
presence of the sp3 hybridized sulfur atom. The seven-membered
ring D also possesses puckered conformations because of the
presence of the S1 atom in 9d and O2 atom in the case of 9c. The
average mean plane angle for the twist between the rings A and C
is 38.69◦ for 9d and 36.49◦ for 9c. The smaller twist angle of 9c as
compared to 9d may be attributed to the presence of the smaller
O2 atom in ring D. The dihedral angle between the rings C and E
in 9d is 44.95◦, while in 9c is merely 4.62◦. The appreciably large
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Fig. 1 Perspective view of 4f, 9c and 9d with atom numbering scheme.
˚
˚
Table 1 Reactants 4 used for the preparation of 9 with their yields and
melting points
A, whilst the distance in 9c between C3 and C19 is 2.970 A, which
˚
is shorter by ~0.4 A as compared to van der Waals radii of two
carbon atoms, and is responsible for a molecular distortion. For
9d the torsion angles C8–C9–C10–C11, C9–C10–C11–C12 and
C10–C11–C12–C13 are -38.71, -10.86 and 110.52◦, respectively.
For 9c the torsion angles C3–C2–C1–C20, C2–C1–C20–C19 and
C1–C20–C19–C18 are 38.01, 12.90 and 152.41◦, respectively.
In order to gain deeper insight into the stereochemical behavior
of the 9c and 9d the helimeric inversion barrier for these com-
pounds was calculated using the quantum chemical methodology.
The energy calculations reveal that the helimerization energy
barriers for 9c and 9d are 20.26 and 18.53 kJ mol-1, respectively.
The calculated values of the inversion barrier of the helimeric
enantiomers indicated a rapid interconversion at room tempera-
ture. The slightly higher energy barrier for 9c as compared to 9d
is possibly due to the presence of the oxygen atom O2 in the seven
membered ring D instead of sulfur. The presence of sulfur atom S2
in 9d may provide better configurational flexibility as compared
to 9c.
The electronic absorption spectrum of 9c recorded in THF
solution displays bands at ~ 450, 300 and 250 nm. The observed
electronic spectrum have been assigned with the help of time-
dependent DFT (TD-DFT) calculations. Since each absorption
line in a TD-DFT spectrum can arise from a several single orbital
excitations, a description of the transition character is generally
not straightforward. However, approximate assignments can be
made, although they provide a simplified representation of the
transitions. TD-DFT excitations were calculated both on the gas
phase and in the solvent using the DCM (dichloromethane). By
comparing the calculated spectra it is evident that calculated
transitions do not exhibit significant solvatochromic effects. In
this view, only the PCM model results are presented, Fig. 2 and 3.
The calculations reveal that the first lower energy band calcu-
lated at 462 nm arises due to the HOMO → LUMO transition
i.e. from p → p*, however, as is apparent from the oscillator
strength (f ), the intensity is relatively weak, therefore this may be
described as a local transition. The next two higher energy bands
calculated at 306 and 256 nm, respectively, also arise from p →
p* transitions without the involvement of the lone pair electrons
of the sulfur atoms. The TD-DFT calculations for 9d indicate
that the nature of electronic transitions is similar to that of the
9c. Similar calculations for compound 4f indicate an electronic
absorption band at 392 nm instead of ~460 nm observed for 9c
9
Reactant 4
Product 9
Mp/◦C
220
Yield (%)
9a
4e
4f
95
80
9b
4e
4f
186
58
57
9c
9d
9e
4c
4d
4e
164
144
110
92
40
38
dihedral angle in the 9d is because of the large S1–C14 bond length
˚
1.777(2) A, while for 9c the O2–C17 bond length is 1.3786(16)
˚
A. Hence, it can be concluded that exchange of the heteroatom
in the seven-membered ring D changes the twist/dihedral angle
and thereby influences the helicity of the molecule. The distance
between the non-bonded carbon atoms C8 and C12 in 9d is 3.049
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Table 2 TD-DFT calculated excitation energies (E), oscillator strengths (f ) and approximate assignments for 4f, 9c and 9d
E/eV
l/nm
f
Composition (%)
Approx. assign.
4f
3.16
3.88
4.94
392
319
251
0.1933
0.2171
0.4091
HOMO → LUMO (44%)
HOMO → LUMO (47%)
HOMO-1 → LUMO+1 (44%)
p → p*, n → p*
p → p*
p → p*, n → p*
9c
2.68
4.05
4.84
462
306
256
0.2228
0.5445
0.1725
HOMO → LUMO (48%)
HOMO-3 → LUMO (35%)
HOMO → LUMO+3 (45%)
p → p*
p → p*
p → p*
9d
2.76
4.12
4.78
449
301
259
0.2019
0.2845
0.1315
HOMO → LUMO (49%)
p → p*
p → p*
p → p*
HOMO-3 → LUMO (41%)
HOMO-3 → LUMO (29%)/
HOMO-2 → LUMO+2 (15%)
Conclusion
In conclusion, we have succeeded to develop an effi-
cient non-catalytic route for the construction of partially
reduced dioxathia- and oxadithiahelicenes through base-
induced inter- and intramolecular C–C bond formation from
the reaction of 4-sec-amino-2-oxo-2,5-dihydrothiochromeno[4,3-
b]pyran-3-carbonitriles (4) with 3,4-dihydro-2H-benzo[b]oxepin-
5(2H)-ones (5a), 3,4-dihydrobenzo[b]thiepin-5(2H)-one (5b) and
thiochroman-4-ones (2) separately. We have studied the effect of
partial reduction as well as the presence of hetero-atom on the
helical parameters. These helical molecules have been obtained
in only two steps in moderate yields. The synthetic strategy is so
flexible that one can prepare a variety of heterohelicenes with more
than two hetero-atoms in the outer helix with amino, nitrile and
halo functionalities which can be further exploited for the ring
construction and functional group transformation. The beauty of
the synthetic protocol lies in obtaining partially reduced heterohe-
licenes without catalytic regioselective hydrogenation. The spatial
distortion of backbone of the helicenes is influenced by helicity
parameters such as bond lengths, dihedral angles and distance
between terminal carbons and hydrogen atoms of the inner helix.
The energy barriers are strongly dependent on the nature of hetero-
atoms introduced in the heterohelicenes which is evidenced from
the helicity parameters and configurational stability.
Fig. 2 Selected orbital excitations for 4f (orbital contour value 0.03).
Experimental section
General
The reagents and the solvents used in this study were of analytical
grade and were used without further purification. The melting
points were determined on an electrically heated Townson Mer-
cer melting point apparatus and are uncorrected. Commercial
reagents were used without purification. 1H and 13C NMR spectra
were measured on a Bruker WM-300 (300 MHz)/Jeol-400 using
CDCl3 and DMSO-d6 as solvents. Chemical shifts are reported
Fig. 3 Selected orbital excitations for 9c (orbital contour value 0.03).
1
in parts per million shift (d-value) from Me4Si (d 0 ppm for H)
and 9d. This relatively higher energy electronic absorption band
is due to the involvement of the n → p* transition in addition
to p → p* (Fig. 2 and 3). The calculated excitation energies and
approximate assignments are presented in Table 2.
or based on the middle peak of the solvent (CDCl3) (d 77.00
ppm for 13C NMR) as the internal standard. Signal patterns
are indicated as s, singlet; d, doublet; dd, double doublet; t,
triplet; m, multiplet. Coupling constants (J) are given in Hertz.
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Infrared (IR) spectra were recorded on a Perkin-Elmer AX-1
spectrophotometer in KBr disc and reported in wavenumbers
(cm-1). ESI-MS spectrometers were used for mass spectra analysis.
13C NMR spectra of compounds 9 and 11 were not reported due
to their very poor solubility in deuterated solvents such as CDCl3
and DMSO-d6 but their structure has also been assigned on the
basis of X-ray diffraction of two representative compounds 9c and
9d.
yield 64%; mp 205–208 ◦C; IR (KBr): 2213 (CN), 1717 (C O)
cm-1; 1H NMR (400 MHz, DMSO-d6): d 3.602 (t, 4H, J = 4.4 Hz, 2
¥ OCH2), 3.786 (t, 4H, J = 4.4 Hz, 2 ¥ NCH2), 3.93 (s, 2H, SCH2),
7.517 (d, 2H, J = 1.2 Hz, Ar-H), 7.714 (t, 1H, J = 1.2 Hz, Ar-H)
ppm; 13C NMR (100 MHz, CDCl3): d 24.21, 51.44, 65.86, 79.57,
79.95, 106.97, 116.14, 124.91, 128.26, 128.81, 130.96, 134.46,
154.44, 159.38, 164.38, 164.78 ppm; MS(CI): m/z = 360 (M+),
332, 292, 274, 247, 169.9; HRMS (ESI): calc. for C17H13ClN2O3S2:
361.0414 (MH+); found: 361.0394.
General procedure for the synthesis of 4-(methylthio)-2-oxo-2,5-
dihydrothiochromeno[4,3-b]pyran-3-carbonitriles (3)
2-Oxo-4-(piperidin-1-yl)-2,5-dihydrothiochromeno[4,3-b]pyran-
3-carbonitrile (4c). Orange coloured crystalline solid; yield 75%;
mp 182–184 ◦C; IR (KBr): 2202 (CN), 1716 (C O) cm-1; 1H NMR
(400 MHz, DMSO-d6): d 1.69 (br s, 6H, 3 ¥ CH2), 3.51 (m, 4H, 2 ¥
NCH2), 3.87 (s, 2H, SCH2), 7.33 (m, 1H, Ar-H), 7.73 (m, 2H, Ar-
H), 7.74 (d, 1H, J = 7.8 Hz) ppm; 13C NMR (100 MHz, CDCl3): d
22.94, 24.72, 25.95 (2C), 52.72 (2C), 79.58, 106.76, 116.62, 126.01,
126.41, 127.22, 127.45, 131.70, 135.83, 155.90, 160.22, 165.51 ppm;
MS(CI): m/z = 324 (M+), 296, 256, 240, 213; HRMS (CI): calc.
for C18H16N2O2S: 324.0932 (M+); found: 324.0939.
A mixture of thiochroman-4-ones (5 mmol) 2 and methyl 2-cyano-
3,3-dimethylthioacrylate 1 (5 mmol) in DMSO (8 mL) was stirred
in the presence of powdered NaOH (7 mmol) for 14 h, at room
temperature. The reaction mixture was poured onto crushed ice
with vigorous stirring. The aqueous suspension was neutralized
with 10% HCl and the precipitate obtained was filtered, washed
with water, dried and crystallized from acetone.
4-(Methylthio)-2-oxo-2,5-dihydrothiochromeno[4,3-b]pyran-3-
carbonitr◦ile (3a). Canary yellow amorphous solid; yield 75%; mp
4-Morpholino-2-oxo-2,5-dihydrothiochromeno[4,3-b]pyran-3-
carbonitrile (4d). Orange coloured crystalline solid; yield 79%;
1
179–180 C; IR (KBr): 2163 (CN), 1682 (C O) cm-1; H NMR
mp 216–218 ◦C; IR (KBr): 2212 (CN), 1714 (C O) cm-1; H
1
(400 MHz, DMSO-d6): d 2.95 (s, 3H, CH3), 4.06 (s, 2H, SCH2),
7.36 (dd, 1H, J = 3.6 Hz, Ar-H), 7.47 (d, 2H, J = 3.6 Hz, Ar-H),
7.80 (d, 1H, J = 8.0 Hz, Ar-H) ppm; 13C NMR (100 MHz, DMSO-
d6): d 17.33, 23.10, 94.54, 109.17, 114.44, 125.43, 126.17, 127.20,
132.01, 135.97, 153.39, 156.82, 166.70 ppm; MS (CI): m/z = 287
(M+), 277, 272, 203, 172, 136; HRMS (CI): calc. for C14H9NO2S2:
287.0075 (M+); found: 287.0084.
NMR (300 MHz, DMSO-d6): d 3.68 (m, 4H, 2 ¥ OCH2), 3.76 (m,
4H, 2 ¥ NCH2), 3.89 (s, 2H, SCH2), 7.32 (m, 1H, Ar-H), 7.743 (m,
2H, Ar-H), 7.74 (d, 1H, J = 7.8 Hz, Ar-H) ppm; 13C NMR (100
MHz, CDCl3): d 24.62, 51.78 (2C), 66.28 (2C), 79.99, 106.66,
116.65, 126.03, 126.45, 127.13, 127.47, 131.81, 135.85, 156.15,
160.06, 165.03 ppm; MS(CI): m/z = 326 (M+), 298, 258, 240,
212; HRMS (CI): calc. for C17H14N2O3S: 326.0759 (M+); found:
326.0756.
9-Chloro-4-(methylthio)-2-oxo-2,5-dihydrothiochromeno[4,3-b]-
pyran-3-carbonitrile (3b). Canary yellow amorphous solid; yield
◦
80%; mp 192–194 C; IR (KBr): 2214 (CN), 1721 (C O) cm-1;
9-Chloro-2-oxo-4-(piperidin-1-yl)-2,5-dihydrothiochromeno[4,3-
1H NMR (300 MHz, CDCl3): d 2.94 (s, 3H, CH3), 4.06 (s, 2H,
SCH2), 7.50 (m, 2H, Ar-H), 7.72 (m, 1H, Ar-H) ppm; 13C NMR
(100 MHz, CDCl3): d 17.79, 23.50, 95.41, 110.21, 114.79, 125.93,
127.33, 129.24, 130.95, 131.88, 135.36, 152.27, 157.02, 166.92 ppm;
MS (CI): m/z = 321 (M+), 308, 277.9, 245, 169.9; HRMS (ESI):
calc. for C14H8ClNO2S2: 321.9763 (MH+); found: 321.9777.
b]pyran-3-carbonitrile (4e). Orange coloured crystalline solid;
◦
yield 57%; mp 240 C; IR (KBr): 2211 (CN), 1712 (C O) cm-1;
1H NMR (300 MHz, DMSO-d6): d 1.68 (br s, 6H, 3 ¥ CH2),
3.51 (br s, 4H, 2 ¥ NCH2), 3.89 (s, 2H, SCH2), 7.49 (s, 2H, Ar-
H), 7.79 (s, 1H, Ar-H) ppm; 13C NMR (100 MHz, CDCl3): d
22.92, 24.75, 25.97 (2C), 52.80 (2C), 79.93, 107.46, 116.50, 125.29,
128.75, 129.18, 130.77, 131.25, 134.85, 154.63, 159.95, 165.24 ppm;
MS(CI): m/z = 324 (M+), 296, 256, 240, 213; HRMS (ESI): calc.
for C18H15ClN2O2S: 359.0621 (M+); found: 359.0619.
General procedure for the synthesis of 4-sec-amino-2-oxo-2,5-
dihydrothiochromeno[4,3-b]pyran-3-carbonitriles (4). A mixture
of 4-(methylthio)-2-oxo-2,5-dihydrothiochromeno[4,3-b]pyran-3-
carbonitriles 3 (1 mmol) and sec-amine (1.1 mmol) was refluxed in
absolute ethanol for 6 h. During this period a precipitate separated
out which was filtered after cooling. The precipitate was washed
with cold ethanol and finally crystallized with acetone.
9-Chloro-2-oxo-4-(pyrrolidin-1-yl)-2,5-dihydrothiochromeno-
[4,3-b]pyran-3-carbonitrile (4f). Orange coloured crystalline
solid; yield 73%; mp 257–260 ◦C; IR (KBr): 2202 (CN), 1700
1
(C O) cm-1; H NMR (300 MHz, DMSO-d6): d 1.92 (s, 4H,
2 ¥ CH2), 3.89 (s, 4H, 2 ¥ NCH2), 4.10 (s, 2H, SCH2), 7.50 (s, 2H,
Ar-H), 7.69 (s, 1H, Ar-H) ppm; 13C NMR (75 MHz, DMSO-d6): d
25.13 (2C), 25.75, 54.16 (2C), 71.41, 105.05, 118.20, 125.27, 128.89,
129.15, 130.80, 130.91, 134.61, 154.45, 159.07, 161.03 ppm; MS
(CI): m/z = 345 (M+ + 1), HRMS (ESI): calc. for C17H13ClN2O2S:
345.0464 (MH+); found: 345.0449.
2-Oxo-4-(pyrrolidin-1-yl)-2,5-dihydrothiochromeno[4,3-b]pyran-
3-carbonitrile (4a). Orange coloured crystalline solid; yield 63%;
mp 230–232 ◦C; IR (KBr): 2197 (CN), 1715 (CO) cm-1; 1H NMR
(400 MHz, DMSO-d6): d 1.91 (s, 4H, 2 ¥ CH2), 3.88 (s, 4H, 2
¥ NCH2), 4.06 (s, 2H, SCH2), 7.31–7.46 (m, 3H, Ar-H), 7.25 (d,
1H, J = 7.6 Hz, Ar-H) ppm; 13C NMR (100 MHz, CDCl3): d
25.61 (2C), 26.24, 54.55 (2C), 71.41, 104.84, 118.83, 126.45, 126.82,
127.87 (2C), 131.80, 136.05, 154.33, 159.78, 161.73 ppm; MS(CI):
m/z = 310 (M+), 282, 242, 213, 187, 136; HRMS (CI): calc. for
C17H14N2O2S2: 310.0776 (M+); found: 310.0772.
9-Chloro-2-oxo-4-(4-phenylpiperazin-1-yl)-2,5-dihydrothiochro-
meno[4,3-b]pyran-3-carbonitrile (4g). Canary yellow crystalline
solid from DCM–methanol; yield 70%; mp 226–258 ◦C; IR (KBr):
1
2213 (CN), 1714 (CO) cm-1; H NMR (300 MHz, DMSO-d6): d
9-Chloro-4-morpholino-2-oxo-2,5-dihydrothiochromeno[4,3-b]-
pyran-3-carbonitrile (4b). Orange coloured crystalline solid;
3.38 (s, 4H, 2 ¥ NCH2), 3.72 (s, 4H, 2 ¥ NCH2), 3.99 (s, 2H,
SCH2), 6.83 (t, 1H, J = 7.2 Hz, Ar-H), 7.00 (d, 2H, J = 8.1 Hz,
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Ar-H), 7.25 (t, 2H, Ar-H), 7.53 (s, 2H, Ar-H), 7.73 (s, 1H, Ar-
H) ppm; 13C NMR (75 MHz, DMSO-d6): d 24.69, 48.72 (2C),
51.20 (2C), 80.59, 107.47, 115.90 (2C), 116.00, 119.54, 125.32,
128.69, 129.22 (2C), 130.80, 131.35, 134.91, 150.37, 154.33, 164.97
ppm; MS (ESI): m/z = 436 (M+ + 1), HRMS (ESI): calc. for
C23H18N3ClO2S: 436.0886 (MH+); found: 436.0877.
ica gel column chromatography using 5–15% chloroform in
hexane.
(Z)-2-(14-Chloro-4-methyl-1,2-dihydro-10H-thiochromeno[3,4-
c]pyrano[3,2-d]benzo[b]oxepine(2H)-ylidene)acetonitrile
Red amorphous solid; yield 95%; mp 219–220 ◦C; UV(CHCl3),
max/nm (e/dm3 mol-1 cm-1): 286 nm (6625); 256 nm (10592); IR
(9a).
l
(KBr): 2142 (–CN) cm-1; 1H NMR (300 MHz, DMSO-d6): d 2.33
(s, 3H, CH3), 2.72 (t, 2H, J = 6.0 Hz, CH2), 3.60 (s, 2H, SCH2),
4.42 (t, 2H, J = 6.0 Hz, OCH2), 5.25 (s, 1H, CH), 7.02 (d, 1H, J =
9.0 Hz, Ar-H), 7.26 (d, 1H, J = 9.0 Hz, Ar-H), 7.43 (dd, 1H, J =
9.0 Hz and 3.0 Hz, Ar-H), 7.63 (m, 2H, Ar-H), 7.83 (s, 1H, Ar-H)
ppm; MS: m/z = 405 (M+), 406 (M+ + 1); HRMS (ESI): m/z calc.
for C23H16ClNO2S: 406.0669 (MH+); found: 406.0662.
2-Oxo-4-(4-phenylpiperazin-1-yl)-2,5-dihydrothiochromeno[4,3-
b]pyran-3-carbonitr◦ile (4h). Canary yellow amorphous solid;
yield 69%; mp 206 C; IR (KBr): 2228 (CN) cm-1; 1H NMR (300
MHz, DMSO-d6): d 2.5 (s, 4H, NCH2), 3.72 (s, 4H, NCH2), 3.96
(s, 2H, SCH2), 6.83 (m, 1H, Ar-H), 7.01 (d, 2H, J = 7.8, Ar-H), 7.25
(t, 2H, J = 7.8, Ar-H), 7.34 (m, 1H, Ar-H), 7.44 (m, 2H, Ar-H),
7.76 (d, 1H, J = 7.8, Ar-H) ppm; 13C NMR (75 MHz, DMSO-d6):
d 24.71, 48.76 (2C), 51.16 (2C), 80.23, 106.76, 115.92 (2C), 116.67,
119.55, 126.07, 126.47, 127.17, 127.49, 129.06 (2C), 131.83, 135.91,
150.41, 156.15, 159.98, 165.23 ppm; MS (ESI): m/z = 402 (M+ +
1), HRMS (ESI): calc. for C23H19N3O2S: 402.1276 (MH+); found:
402.1270.
(Z)-2-(14-Chloro-4,6-dimethyl-1,2-dihydro-10H-thiochromeno-
[3,4-c]pyrano[3,2-d]benzo[b]oxepine(2H)ylidene)acetonitrile (9b).
Red amorphous solid; yield 58%; mp 184–186 ◦C; IR (KBr): 2191
(–CN) cm-1; 1H NMR (300 MHz, DMSO-d6): d 2.35 (s, 3H, CH3),
2.49 (t, 2H, J = 6.3 Hz, CH2), 2.54 (s, 3H, CH3), 3.31 (s, 2H,
SCH2), 4.45 (s, 1H, CH), 4.58 (t, 2H, J = 6.3 Hz, OCH2), 6.84 (s,
1H, Ar-H), 6.95 (s, 1H, Ar-H), 7.29 (d, 1H, J = 2.1 Hz, Ar-H),
7.41 (d, 1H, J = 1.8 Hz, Ar-H), 7.47 (m, 1H, Ar-H) ppm; MS:
m/z = 420 (M+ + 1); HRMS (ESI): m/z calc. for C24H18ClNO2S:
420.0825 (MH+); found: 420.0822.
4-(4-Benzylpiperazin-1-yl)-2-oxo-2,5-dihydrothiochromeno[4,3-
b]pyran-3-carbonitrile (4i). Canary yellow crystalline solid from
DCM–methanol; yield 76%; mp 196–198 ◦C; IR (KBr): 2206
(CN), 1714 (C O) cm-1; 1H NMR (300 MHz, DMSO-d6): d 2.43
(s, 4H, 2 ¥ NCH2), 2.50 (s, 4H, 2 ¥ NCH2), 3.51 (s, 2H, SCH2), 3.81
(s, 2H, CH2), 7.21 (m, 1H, Ar-H), 7.26 (m, 5H, Ar-H), 7.34–7.38
(m, 2H, Ar-H), 7.68 (m, 1H, Ar-H) ppm; 13C NMR (75 MHz,
DMSO-d6): d 24.90, 51.53 (2C), 52.71 (2C), 61.61, 89.75, 106.45,
115.55, 118.80, 119.80, 126.08, 126.49, 127.14, 127.50, 128.30 (2C),
128.92 (2C), 131.84, 135.71, 137.73, 147.35, 184.00ppm;MS(ESI):
m/z = 416 (M+ + 1); HRMS (ESI): calc. for C24H21N3O2S: 416.1433
(MH+); found: 416.1430.
(Z)-2-(14-Chloro-6-methyl-1,2-dihydro-10H-thiochromeno[3,4-
c]pyrano[3,2-d]benzo[b]oxepine(2H)-ylidene)acetonitrile
(9c).
Red crystalline solid; yield 92%; mp 163–164 ◦C; IR (KBr): 2197
(–CN) cm-1; 1H NMR (300 MHz, DMSO-d6): d 2.30 (s, 3H, CH3),
2.70 (br s, 2H, CH2), 3.54 (s, 2H, SCH2), 4.46 (br s, 2H, OCH2),
5.23 (s, 1H, CH), 7.00 (m, 1H, Ar-H), 7.23 (m, 1H, Ar-H), 7.33
(m, 2H, Ar-H), 7.54 (m, 2H, Ar-H), 7.72 (m, 1H, Ar-H); MS:
m/z = 372 (M+ + 1); HRMS (ESI): m/z calc. for C23H17ClNO2S:
372.1058 (MH+); found: 372.1041.
Synthesis of 11-chloro-6,7-dihydro(bisthiochromeno[b,e])pyrano-
[3,4-c]pyran-14,15-dione (8). A mixture of 4-(methylthio)-2-oxo-
2,5-dihydrothiochromeno[4,3-b]pyran-3-carbonitriles 3 (1 mmol)
and 6-methylthiochroman-4-one (2b) and powdered KOH
(1.2 mmol) in DMSO (3 mL) was stirred at room temperature
for 14 h. After completion, reaction mixture was poured onto
crushed ice with vigorous stirring and neutralized with 10% HCl.
The crude product obtained was filtered off, washed with water
and finally purified by silica gel column chromatography using 5–
45% chloroform in hexane. Orange colored solid; yield 43%; mp
211–212 ◦C; IR (KBr): 1769 (C O), 1670 (C O) cm-1; 1H NMR
(300 MHz, DMSO-d6): d 3.85 (s, 2H, SCH2, merged in H2O), 4.10
(s, 2H, SCH2), 7.26–7.41 (m, 5H, Ar-H), 7.68 (m, 1H, Ar-H), 7.91
(m, 1H, Ar-H) ppm; HRMS (ESI): m/z calc. for C22H11ClO4S2:
437.9787 (M+); found: 438.0001.
(Z)-2-(1,2-Dihydro-10H -thiochromeno[3,4-c]pyrano[3,2-d]-
benzo[b]thiaoxepine(2H)-ylidene)acetonitrile (9d). Red amor-
phous solid; yield 40%; mp 142–144 ◦C; IR (KBr): 2196 (–CN)
1
cm-1; H NMR (300 MHz, CDCl3): d 2.44 (t, 2H, J = 6.6 Hz,
CH2), 3.32 (s, 2H, SCH2), 3.66 (t, 2H, J = 6.6 Hz, SCH2), 4.49 (s,
1H, CH), 7.29 (m, 2H, Ar-H), 7.39 (m, 1H, Ar-H), 7.53 (m, 3H,
Ar-H), 7.69 (d, 1H, J = 7.2 Hz, Ar-H), 7.82 (d, 1H, J = 7.5 Hz,
Ar-H) ppm; MS: m/z = 374 (M+ + 1); HRMS (ESI): m/z calc. for
C22H15NOS2: 374.0673 (MH+); found: 374.0641.
(Z)-2-(14-Chloro-1,2-dihydro-10H-thiochromeno[3,4-c]pyrano-
[3,2-d]benzo[b]thiaoxepine(2H)-ylidene)acetonitrile
(9e). Red
amorphous solid; yield 38%; mp 108–110 ◦C; IR (KBr): 2185
1
(–CN) cm-1; H NMR (300 MHz, DMSO-d6): d 2.58 (br s, 2H,
General procedure for the synthesis of (Z)-2-(1,2-dihydro-10H-
thiochromeno[3,4-c]pyrano[3,2-d]benzo[b]oxepine(2H)-
ylidene)acetonitriles (9)
CH2), 3.70 (br s, 2H, SCH2), 3.93 (m, 2H, SCH2), 4.57 (s, 1H, CH),
7.38 (m, 4H, Ar-H), 7.48 (m, 1H, Ar-H), 7.57 (m, 1H, Ar-H), 7.70
(m, 1H, Ar-H) ppm; MS: m/z = 408 (M+ + 1); HRMS (ESI): m/z
calc. for C22H14ClNOS2: 408.0284 (MH+); found: 408.0279.
A mixture of 4-sec-amino-2-oxo-2,5-dihydrothiochromeno[4,3-
b]pyran-3-carbonitrile
4
(1.0 mmol) and 3,4-dihydro-2H-
2-(5-Chloro-1H-dithiochromeno[4,3-b:4¢,3¢-d]pyran-14(7H)-yl-
benzo[b]oxepin/thiepin-5(2H)-one 5 (1 mmol) and powdered
NaOH (1.2 mmol) in DMSO (3 mL) was stirred at room
temperature for 14 h. After completion, reaction mixture was
poured onto crushed ice with vigorous stirring and neutral-
ized with 10% HCl. The crude product obtained was fil-
tered off, washed with water and finally purified by sil-
idene)acetonitrile (11a).
A
mixture of 4g (1.0 mmol),
thiochroman-4-one 2 (1 mmol) and powdered KOH (1.2 mmol)
in DMF (3 mL) was stirred at room temperature for 14 h.
After completion, the reaction mixture was poured onto crushed
ice with vigorous stirring and neutralized with 10% HCl. The
crude product obtained was filtered off, washed with water and
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finally purified by a silica gel column chromatography using 45%
chlorofor◦m in hexane as an amorphous red solid; yield 25%; mp
R indices (all data): R1 = 0.0746, wR2 = 0.1430, GOF = 1.038;
largest difference peak and hole: 0.425 and -0.372 e A .
-3
˚
1
218–220 C; IR (KBr): 2191 (–CN) cm-1; H NMR (300 MHz,
Crystal data for 9c. C23H17NO2S, Mr = 371.44, monoclinic,
CDCl3): d 3.32 (s, 2H, SCH2), 3.81 (s, 2H, SCH2), 4.53 (s, 1H,
CH), 7.32 (m, 6H, Ar-H), 7.50 (m, 1H, Ar-H) ppm; MS: m/z =
394 (M+ + 1); HRMS (ESI): m/z calc. for C21H12ClNOS2: 394.0127
(MH+); found: 394.0110.
˚
space group ◦P21/n, a = 7.723(2), b = 9.374(4), c = 24.947(7) A,
3
-3
˚
b = 95.26(3) , V = 1798.5(10) A , Z = 4, Dc = 1.372 Mg m ,
linear absorption coefficient 0.198 mm-1, F(000) = 776, crystal size
0.75 ¥ 0.28 ¥ 0.182 mm, reflections collected 21353, independent
reflections 4276 [Rint = 0.0721], final indices [I > 2s(I)]: R1 =
0.0391, wR2 = 0.1006; R indices (all data): R1 = 0.0520, wR2 =
0.1074, GOF = 1.020; largest difference peak and hole: 0.235 and
2-(7,8-Dihydrobenzo[f ]thiochromeno[4,3-c]isochromen-6(13H)-
ylidene)acetonitrile (11b). Compound 11b was prepared
from the reaction of 5,6-dihydro-4-(4-methylpiperazin-1-yl)-2-
oxobenzo[h]chromene-3-carbonitrile and thiochroman-4-one in
the presence of powdered KOH. Usual work-up and crystallization
from chloroform and hexane (3 : 1) gave red rod shaped crystals;
yield 30%; mp 253–254 ◦C; IR (KBr): 2187 (CN) cm-1; 1H NMR
(300 MHz, CDCl3): d 2.35 (t, 2H, J = 7.2, Hz, CH2), 2.82 (t, 2H,
J = 7.2 Hz, CH2), 3.98 (s, 2H, SCH2), 4.46 (s, 1H, CH), 7.28–7.31
(m, 7H, Ar-H), 7.99 (m, 1H, Ar-H) ppm; MS: m/z = 342 (M+ + 1);
HRMS (ESI): m/z calc. for C22H15NOS: 342.0953 (MH+); found:
342.0951.
-3
˚
-0.231 e A .
Crystal data for 9d. C22H15NOS2, Mr = 373.47, monoclinic,
space group P21/c, a = 11.8038, b = 16.2989(5), c = 19.3777(8)
◦
3
-3
˚
˚
A, b = 105.682(2) , V = 3589.3(2) A , Z = 8, Dc = 1.382 Mg m ,
linear absorption coefficient 0.307 mm-1, F(000) = 1552, crystal
size 1.16 ¥ 0.52 ¥ 0.21 mm, reflections collected 48753, independent
reflections 13628 [Rint = 0.1175], final indices [I > 2s(I)]: R1 =
0.0844, wR2 = 0.1800; R indices (all data): R1 = 0.1403, wR2 =
0.2007, GOF = 1,176; largest difference peak and hole 0.759 and
-3
˚
-0.518 e A .
2-(3-Chloro-7,8-dihydrobenzo[f ]thiochromeno[4,3-c]isochro-
men-6(13H)-ylidene)acetonitrile (11c). Compound 11c was
obtained from the reaction of 5,6-dihydro-4-(4-methylpiperazin-
Computational details
1-yl)-2-oxobenzo[h]chromene-3-carbonitrile
and
6-chloro-
Density functional theory (DFT) calculations have been per-
formed using the Gaussian 03 program.34 The optimized ground
and transition-state geometries were calculated using the B3LYP
exchange–correlation functional35 and using GDIIS36 algorithm.
The triple zeta 6-311+G* basis set for all atoms and tight SCF
convergence criteria were used for the geometry optimization. For
ground state optimization, wave function stability calculations
were performed to confirm that the calculated wave functions
corresponded to the ground state. The presence of one negative fre-
quency was observed in the case of the transition-state geometries.
The optimized ground state structures of the compounds were used
for molecular orbital analyses and time-dependent DFT (TD-
DFT) calculations at the B3LYP/6-311G** level of theory with
the polarized continuum model (PCM).37 The solvent parameters
were those of the tetrahydrofuran. The energies and intensities
of the 30 lowest energy spin-allowed electronic excitations were
calculated using TD-DFT.
thiochroman-4-one and worked up as described above. red
amorphous solid; yield 35%; mp 266–268 ◦C; IR (KBr): 2185
1
(CN) cm-1; H NMR (300 MHz, CDCl3): d 2.35 (t, 2H, J = 7.2
Hz, CH2), 2.82 (t, 2H, J = 7.2 Hz, CH2), 3.98 (s, 2H, SCH2), 4.50
(s, 1H, CH), 7.47 (m, 6H, Ar-H), 7.92 (s, 1H, Ar-H) ppm; MS:
m/z = 376 (M+ + 1); HRMS (ESI): m/z calc. for C22H14ClNOS:
376.0563 (MH+); found: 376. 0545.
X-Ray diffraction studies
Intensity data for the colorless crystals of 4f, 9c and 9d were
collected at 132(2) K on a Bruker APEX-II CCD diffractometer
system equipped with graphite-monochromated Mo-Ka radiation
˚
l = 0.71073 A. The final unit cell determination, scaling of the
data and corrections for Lorentz and polarization effects were
performed with Bruker SAINT.30 Symmetry-related multiscan
absorption corrections have been applied. In the case of 9d no
absorption correction was applied. The structures were solved by
direct methods (SHELXS-97)31 and refined by a full-matrix least-
squares procedure based on F2.32 All non-hydrogen atoms were
refined anisotropically; hydrogen atoms were located at calculated
positions and refined using a riding model with isotropic thermal
parameters fixed at 1.2 times the Ueq value of the appropriate
carrier atom. For 4f the Flack’s parameter was 0.48(6), which
suggests that the solved structure is absolute. Figures for the
compounds were prepared using ORTEP.33 The relevant crystal
and refinement parameters for the compounds 4f, 9c and 9d (Fig.
1) are shown below.
Acknowledgements
H. K. M., V. K. T. and V. J. R. are thankful to CSIR, New Delhi,
India for financial support [project No-01(2280)/08/EMR-II] and
Sophisticated Analytical Instrument Facility, CDRI, Lucknow,
India and Department of Chemistry, University of Saarland,
Saarbrucken, Germany for providing spectroscopic data.
References
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p. 543; (d) W. H. Laarhoven and W. J. C. Prinsen, Top. Curr. Chem.,
1984, 125, 63.
Crystal data for 4f. C17H13ClN2O2S, Mr = 344.80, orthorhom-
bic, space group Pca21, a = 8.7105(6), b = 8.3893(6), c = 41.097(3)
3
-3
˚
˚
A, V = 3003.2(4) A , Z = 8, Dc = 1.525 Mg m , linear absorption
coefficient 0.404 mm-1, F(000) = 1424, crystal size 0.93 ¥ 0.44 ¥
0.13 mm, reflections collected 54973, independent reflections 9542
[Rint = 0.1281], final indices [I > 2s(I)]: R1 = 0.0562, wR2 = 0.1334;
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