Unique type II halogen ... halogen interactions in pentafluorophenyl-appended 2,2'-bithiazoles

Article abstract of DOI:10.1021/cg3012298

Herein, we report the design and synthesis of 2,2'-bithiazole derivatives with efficient intermolecular halogen interactions. The single crystal X-ray diffraction studies revealed unique type-II halogen interactions in these derivatives. The shortest type-II F ... F interactions within the distance of 2.67 A, at an angle of 89.1° and 174.2°, was observed for the first time. The Gaussian calculations were performed to further establish predominant F ... F interactions.

Full text of DOI:10.1021/cg3012298

Article
pubs.acs.org/crystal
Unique Type II Halogen···Halogen Interactions in Pentafluorophenyl-
Appended 2,2′-Bithiazoles
Published as part of the Crystal Growth & Design virtual special issue in honor of Prof. G. R. Desiraju.
Raja Bhaskar Kanth Siram,‡ Durga Prasad Karothu,‡ Tayur N. Guru Row,* and Satish Patil*
Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India
S
* Supporting Information
ABSTRACT: Herein, we report the design and synthesis of 2,2′-bithiazole derivatives with efficient intermolecular halogen
interactions. The single crystal X-ray diffraction studies revealed unique type-II halogen interactions in these derivatives. The
shortest type-II F···F interactions within the distance of 2.67 Å, at an angle of 89.1° and 174.2°, was observed for the first time.
The Gaussian calculations were performed to further establish predominant F···F interactions.
he burgeoning attention on fluorinated organic com-
pounds has been important for the last 17 years, due to
interactions are classified into two types, type I (cis and trans)
with θ1 ≈ θ2 and type II with θ1 ≈ 90° and θ2 ≈ 180°, as
depicted in Figure 1.11 Type II interactions are formed through
polarization of halogen atoms, whereas type I interactions are
caused by close packing and do not form stabilizing
interactions.1,11 Over the years, type II interaction has grabbed
more attention and have been further substantiated by several
splash reports showing these halogen−halogen interactions.12
A CSD search (version 1.14, 2012) shows 5347 molecules
containing X-F···F-X (where X is any element) type I and type
II interactions at distances ranging from 2.0 to 3.2 Å. Figure 2
depicts 614 hits of these, which show type II F···F interactions
where the angles were restricted to θ1= 60−90° and θ2 = 150−
180°. The number reduces to only 2 cases when the distance
range is shortened to 2.6−2.7 Å. With a restriction of the angles
to θ1 = 80−90° and θ2 = 170−180° in the CSD search, while
keeping the distance range as 2.0−3.2 Å, 52 molecules are
observed to show these interactions. Further shortening of the
F···F distance to 2.6−2.7 Å (θ1 = 80−90° and θ2 = 170−180°)
shows no hits. This has captivated our attention to synthesize
fluorinated derivatives and exploiting shorter F···F interactions
within the proximate angle range. We have explored 2,2′-
T
their applications in life science. From its early inception of
fluorine as a vital element in drugs, there have been a large
number of publications on fluorinated drugs.1 However, not
many applications of fluorinated compounds is seen in the
domain of opto-electronics. In general, electron-withdrawing
groups like fluorine, cyano, and nitro, etc. or electron donating
substituents such as alkoxy, alkylamino, etc. can lower or raise
the energies of the highest occupied molecular orbital
(HOMO) and the lowest unoccupied molecular orbital
(LUMO) relative to the unsubstituted system.2 The redox
and optical properties of the heterocyclic derivatives can be
altered by the substitution of electron-donating or electron-
withdrawing groups.3,4 These modifications ultimately affect the
physical and chemical properties of the resultant derivatives and
define its role in various device configurations.5
Replacing hydrogen atoms by fluorine can profoundly vary
the physical and chemical properties of compounds caused by
its electronegativity, low polarizability, bond strength, and even
the electron density distribution.6−8 Because of these vivid
properties, fluorine has an immense influence on inter- and
intramolecular interactions.9 Even though fluorine is a highly
electronegative element, it forms difluorine rather than
repelling another fluorine.10 This leads to having prolonged
snoop on the X-F···F-X interaction until now. With dependance
on the geometry of the halogen atoms, halogen−halogen
Received: August 25, 2012
Revised: February 11, 2013
Published: February 11, 2013
© 2013 American Chemical Society
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Figure 1. Graphical representation of type I (cis and trans) and type II F···F interactions.
light the attenuated type II halogen−halogen (fluorine and
bromine) short contacts by single crystal X-ray diffraction
studies.
Scheme 1 illustrates the synthesis and molecular structure of
the new bithiazole derivative, 4,4′-bis(perfluorophenyl)-2,2′-
bithiazole (PFBT). PFBT was synthesized in high yield (83%)
through the Hantzsch thiazole synthesis, by the condensation
of 2-bromo-1-(perfluorophenyl) ethanone with dithiooxamide
in ethanol under reflux conditions. After filtration of the solid,
product was recrystallized by the slow evaporation of its
saturated solution in ethanol. Our attempts of the dibromina-
tion of PFBT with standard brominating procedures like NBS
in different solvents, AcOH, CHCl3, THF, or AcOH − CHCl3
(1:1) and bromine gas in CHCl3, did not succeeded. Finally,
our attempt at bromination under strong acidic solvent
conditions, such as trifluoroacetic acid, provided the dibromi-
nated product (Br-PFBT). All these derivatives are charac-
terized by H, 19F, and 13C NMR.
1
Figure 2. CSD search for number of molecules showing F···F
interactions, where the angles θ1= 60−90° and θ2 = 150−180°.
Criteria: distances (2.0−3.2 Å, no ions, not disordered, only organics,
and intermolecular contacts).
Single crystal X-ray diffraction data sets were collected on an
Oxford Xcalibur (Mova) diffractometer equipped with an EOS
CCD detector using MoKα radiation (λ = 0.71073 Å).16 The
crystal was maintained at 110 K during data collection using the
Oxford Instruments Cryojet-HT controller.17 All structures
were solved by direct methods using SHELXS-97 and refined
against F2 using SHELXL-97.18 H atoms were located
geometrically and refined isotropically. The WinGX package
was used for refinement and production of data tables and
ORTEP-3 for structure visualization and making the molecular
representations.19,20 Analysis of the H-bonded and π···π
interactions was carried out using PLATON for all the
structures.21 Packing diagrams were generated using MER-
CURY.22
bithiazole-based derivatives to study the halogen···halogen
interactions by substitution with pentafluorophenyl group.
2,2′-Bithiazoles are a very important class of heterocycles, in
which an imine nitrogen is substituted in place of the carbon
atom at the 3 position of thiophene, which facilitates the
electron withdrawing nature to the five-membered ring, due to
the high electron affinity of the nitrogen atom. These
derivatives are widely used in a variety of applications which
include organic light-emitting diodes, organic solar cells, and
field-effect transistors.13−15 We report, herein, synthesis of
pentafluorophenyl appended bithiazole derivatives and high-
The single crystals of compounds PFBT and Br-PFBT
suitable for X-ray diffraction analyses were efficaciously
Scheme 1. Synthesis of Pentafluorophenyl-Appended Bisthiazole Derivative
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Figure 3. (a) ORTEP diagram of compound PFBT with displacement ellipsoids at a 50% probability level at 110 K. (b) Packing diagram of
compound PFBT along the a axis showing type I and type II F···F contacts along with π···π stacking.
obtained by slow evaporation of ethanol at ambient temper-
atures. Both compounds, PFBT and Br-PFBT, are exhibiting
the type II halogen contacts (Table S2 of the Supporting
Information). The compound PFBT23 crystallizes in a
monoclinic space group P21/n with Z = 2 and Z′ is 1/2. In
crystal packing, molecules are arranged in herringbone packing
along the a direction (Figure 3b). The packing shows habitual
type I F···F contacts in between F4 and F2 of two adjacent
molecules at a distance of 2.83 Å, where the angles are 137.4°
and 135.9° for ∠C5″-F2″···F4 and ∠C3−F4···F2″, respectively
(Figure 3). The structure determined for PFBT exhibited the
type II fluorine contacts at a short distance of 2.67 Å in between
the F5 and F3 of the two adjacent molecules, where the angles
are θ1 = 89.1° and θ2 = 174.2° for ∠C4′-F3′···F5 and ∠C2−
F5···F3′, respectively (Figure S1 of the Supporting Informa-
tion). As mentioned earlier, the CSD search reveals only two
molecules (distance: 2.6−2.7 Å, angles: 60−90° and 150−
180°), where the first molecule confirms type II contact at a
functional of Lee, Yang, and Parr29 (B3LYP keyword in
Gaussian09). Basis set superposition errors (BSSEs) were
accounted for the counterpoise correction method.30 From
these calculations, it was found that the dimer interaction
energy is 8.1 kJ/mol, confirming the attractive nature of the
type II F···F interaction.
HIRSHFELD SURFACE ANALYSIS
■
Further, the intermolecular contacts in the crystal structure of
PFBT are quantified via the Hirshfeld surface analysis,31,32
using the crystal explorer.33 Through the Hirshfeld surface
analysis, one can visualize the intermolecular interactions in
crystal structures.34,35 In the current study, the contacts
involving F atoms and H···F are mainly estimated. The
percentage of contributions to the Hirshfeld surface areas for
these contacts and “other” (F···C, C···S, C···C, H···S, and
N···C) intermolecular contacts are shown in Figure S3 of the
Supporting Information. The analysis shows the F···F halogen
contact as the dominating one (45.0%) in terms of Hirshfeld
surface sharing, whereas only ∼12% contribution comes from
the H···F contacts. The C···F and C···C contacts both
contribute ∼30.0% to the Hirshfeld surface areas. However, it
is notable that these percentage contributions do not
distinguish between the close and distant contacts. The major
contacts C−F···F−C halogen contacts are predominantly
highlighted by conventional mapping of dnorm on molecular
Hirshfeld surfaces (Figure 4). The dark red spots on the
Hirshfeld surfaces indicate the F···F interaction.
24
́
distance of 2.68 Å, in which the angles were 88.1° and 160.6°.
The second molecule shows angles 87.7° and 163.4°,
25
́
respectively, where the distance is 2.69 Å. Apart from having
a shorter F···F contact, the PFBT molecule shows π···π stacking
between the thiazole rings and the phenyl rings. The distance
between cg(1a) and cg(thiazole)(2b) is 3.58 Å, whereas the
same remains for cg(1b′) and cg(thiazole)(2a′) (Figure S2 of
the Supporting Information).
Seik Weng Ng has reported the structure of the phenyl
derivative which shows no specific or significant interactions in
the packing.26 Substitution of hydrogen by fluorine provides
evidence for strong intermolecular type II halogen−halogen
interactions and π···π stacking. This molecule demonstrates the
type I and type II fluorine contacts which were depicted in
Figure 3b.
The energies of monomer PFBT and its dimer were
calculated using Gaussian09. Single crystal coordinates were
used as input for calculations. These Gaussian calculations
employed the split-valence double-exponential 6-31G++(d,p)
basis sets with polarization functions.27 DFT calculations in
Gaussian09 were performed with Becke’s three-parameter
hybrid method,28 combined with the nonlocal correlation
Substitution of bromine in place of hydrogen atoms in PFBT
leads the compound Br-PFBT36 to crystallizes in a monoclinic
space group P21/c with Z = 2, whereas Z′ = 1/2. The hydrogen
atoms in the compound PFBT are replaced by bromine atoms
in this molecule, which shows significant variability from
compound PFBT in packing. The molecules are arranged in a
herringbone manner (Figure 5b), even though the size,
electronegativity, and the repulsion between fluorine and
bromine leads to the twisting of two pentafluorophenyl rings
at a dihedral angle of 59.2°.This guided the packing of Br-PFBT
to be different from that of compound PFBT. Prior to our
attention, this compound also shows type II halogen−halogen
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures regarding synthesis and NMR spectra
of the derivatives, packing diagrams, and the full crystallo-
graphic details of the derivatives. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: satish@sscu.iisc.ernet.in and ssctng@sscu.iisc.ernet.in.
■
Author Contributions
Figure 4. dnorm mapped on Hirshfeld surfaces for visualizing the F···F
contacts.
‡These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
interactions between bromine atoms at a distance of 3.68 Å,
where the angles are 68.9° and 174.8° for ∠C7−Br1···Br1′ and
∠C7′-Br1′···Br1, respectively (Figure S4 of the Supporting
Information). Further stability is imparted by the S···F
interactions at a distance of 3.20 Å.
■
S.P. thanks ISRO for supporting this work through the project
ISTC/CSS/STP/252 and S.R.B.K. and D.P.K. thank CSIR for
the Senior Research Fellowship. T.N.G. thanks the DST, New
Delhi for the J. C. Bose Fellowship.
In conclusion, the pentafluorophenyl appended 2,2′-
bithiazole derivative was synthesized for the first time. The
single crystal X-ray studies show the unusual strong type II
F···F interactions, where θ1 and θ2 are proximate to 90° and
180°, respectively. PFBT also shows usual type I F···F
interactions. From the Gaussian calculations, it is found that
the interaction between both fluorine atoms is attractive and
Hirshfeld surfaces confirm that the F···F contacts are
predominant. Upon bromination, the type II Br···Br interaction
was observed and the packing was further stabilized by the
S···Br interactions. Charge density studies of these type II
interactions and device fabrication is an ongoing work in our
laboratory. Further work will focus on the extension of the
conjugation with different aromatic and heteroaromatic
substituents.
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