Isomorphous methyl-and chloro-substituted small heterocyclic analogues obeying the chlorine-methyl (Cl-Me) exchange rule

organic compounds

Acta Crystallographica Section C

Crystal Structure

Communications

dimerizable cyclopentanones (Jones et al., 1981) and certain

coumarins (Gnanaguru et al., 1984) showed that the Cl–Me

exchange rule, based solely on the size of the substituent, need

not always be valid. Desiraju & Sarma (1986) observed that

this rule is a valid proposition only for large irregularly shaped

molecules, preferably with one Cl atom; however, it is not

necessarily true for more planar and regular-shaped molecules

where short Clꢀ ꢀ ꢀCl contacts, which may be incompatible with

the geometrical model, inﬂuence the molecular interactions.

The crystal structures analysed in the present study, namely

[3-methyl-4-(4-methylphenyl)-1-phenyl-6-triﬂuoromethyl-1H-

pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-yl)methanone, (I),

and [4-(4-chlorophenyl)-3-methyl-1-phenyl-6-triﬂuoromethyl-

1H-pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-yl)methanone,

(II), are good examples of a case where the Cl–Me exchange

ISSN 0108-2701

Isomorphous methyl- and chloro-

substituted small heterocyclic

analogues obeying the chlorine–

methyl (Cl–Me) exchange rule¹

V. Rajni Swamy,^aP. Muller,^bN. Srinivasan,^aS. Perumal^c

¨

and R. V. Krishnakumar^a*

^aDepartment of Physics, Thiagarajar College, Madurai 625 009, India, ^bX-Ray

Diffraction Facility, MIT Department of Chemistry, 77 Massachusetts Avenue,

Building 2, Room 325, Cambridge, MA 02139-4307, USA, and ^cSchool of

Chemistry, Madurai Kamaraj University, Madurai 625 021, India

Correspondence e-mail: mailtorvkk@yahoo.co.in

Received 20 September 2012

Accepted 19 February 2013

Online 6 March 2013

The two new isomorphous structures [3-methyl-4-(4-methyl-

phenyl)-1-phenyl-6-triﬂuoromethyl-1H-pyrazolo[3,4-b]pyri-

din-5-yl](thiophen-2-yl)methanone, C₂₆H₁₈F₃N₃OS, (I), and

[4-(4-chlorophenyl)-3-methyl-1-phenyl-6-triﬂuoromethyl-1H-

pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-yl)methanone, C₂₅H₁₅-

ClF₃N₃OS, (II), are shown to obey the chlorine–methyl

exchange rule. Both structures show extensive disorder,

treatment of which greatly improves the quality of the

description of the structures. In addition, it is worth noting

that the presence of extensive disorder may make it difﬁcult to

detect the isomorphism automatically during data-mining

procedures (such as searches of the Cambridge Structural

Database).

rule holds. In addition, the reported crystal structures are

potential candidates for remaining unnoticed for their

isomorphism in the Cambridge Structural Database (Allen,

2002) due to the extensive disorder observed in both of them.

Comment

The prediction of crystal structures is still a major challenge

for crystallographers owing to the complex nature of mol-

ecular interactions that range from the robust to the weak.

Hence, reliable crystallographic studies of the effect of

substituents on the packing of molecules in crystals are

essential for understanding the nature and strength of inter-

molecular interactions with the goal of classifying and ulti-

mately predicting them. Since the ﬁrst use of the term ‘crystal

engineering’ by G. M. J. Schmidt (1971), the close-packing

model for organic molecules based on pure geometrical

considerations (Kitaigorodskii, 1973) that led to the chlorine–

methyl (Cl–Me) exchange rule may well be considered a

signiﬁcant ﬁrst step towards crystal-structure prediction.

Subsequently, crystal-engineering studies on selected photo-

Figure 1

The molecular structure of (I), showing the atom-numbering scheme and

displacement ellipsoids drawn at the 50% probability level. H atoms and

atoms of the minor disorder components have been omitted for clarity.

¹This paper is dedicated to the memory of Professor M. A. Viswamitra on the

occasion of the 12th anniversary of his death.

412 # 2013 International Union of Crystallography

doi:10.1107/S0108270113004812

Acta Cryst. (2013). C69, 412–415

organic compounds

The crystal structures of compounds (I) and (II) (Figs. 1

and 2) are relevant in the above context since they differ from

each other only by a methyl group in (I) being replaced by a Cl

atom in (II). The replacement of Me by Cl has not caused any

signiﬁcant change in their unit-cell parameters, lattice type,

space group and intermolecular interaction pattern, i.e. (I) and

(II) are isomorphous and isostructural. Interestingly, the –CF₃

groups and the thiophene rings in both (I) and (II) exhibit

disorder, the proper treatment of which signiﬁcantly improved

the crystal structures (see Reﬁnement; Fig. 3). For example,

residual electron density between the methyl H atoms became

apparent only after the –CF₃group disorder had been

addressed appropriately; the initial model corresponding to a

simple rotation about the C5—C25 bond was not sufﬁcient to

reveal the methyl-group disorder. This example underlines the

importance of reﬁning disorder carefully and accurately,

because even though the simpler disorder model would have

been considered acceptable by most standards, only the

improved model paved the way for further improvement.

The weak noncovalent crystal-packing interactions are

similar in both (I) and (II) (Tables 1 and 2).

Figure 2

The molecular structure of (II), showing the atom-numbering scheme and

displacement ellipsoids drawn at the 50% probability level. H atoms and

atoms of the minor disorder components have been omitted for clarity.

There are two C—Hꢀ ꢀ ꢀO hydrogen bonds, one leading to

the formation of centrosymmetric dimers and the other linking

these pairs into double chains along [011] (Fig. 4). There is a

signiﬁcant ꢀ–ꢀ interaction [Cg1ꢀ ꢀ ꢀCg2ⁱⁱ; Cg1 is the centroid of

the pyrazole ring and Cg2 that of the phenyl ring attached to

the pyrazole ring; symmetry code: (ii) ꢁx + 1, ꢁy + 1, ꢁz + 1]

between centrosymmetric pairs within the chain (Fig. 5), with

ii

˚

Cg1ꢀ ꢀ ꢀCg2 values of 3.9140 (9) and 3.9319 (10) A in (I) and

(II), respectively. The C15ꢀ ꢀ ꢀO1ⁱand H15ꢀ ꢀ ꢀO1ⁱdistances in

(II) [symmetry code: (i) x, y ꢁ 1, z ꢁ 1] are noticeably

˚

lengthened, with values of 3.610 (2) and 2.74 A, respectively,

˚

compared with values of 3.531 (2) and 2.66 A in (I). However,

the geometries of these bonds remain essentially identical, as

can be seen from the C—Hꢀ ꢀ ꢀO angle of 156^ꢂin both struc-

tures. The longer Cꢀ ꢀ ꢀO contact in (II) is recognized as a

hydrogen bond since the angle tends towards linearity and

asserts the need to inspect the intermolecular contacts more

Figure 3

The molecular structure of (I), showing the disordered components of the

thiophene ring, the –CF₃group and the benzyl methyl group. The

disorder observed in (II) is nearly identical to that in (I).

Figure 4

The role of C—Hꢀ ꢀ ꢀO hydrogen bonds leading to the formation of double chains along [011] in (I). Nonparticipating H atoms, methyl C atoms,

thiophene rings and the minor component of the disordered –CF₃group have been omitted for clarity. The corresponding ﬁgure for (II) is identical.

ꢃ

Acta Cryst. (2013). C69, 412–415

Rajni Swamy et al.

C₂₆H₁₈F₃N₃OS and C₂₅H₁₅ClF₃N₃OS 413

organic compounds

with ethyl acetate (2 ꢄ 40 ml). After removal of the solvent, the

residue was chromatographed over silica gel (230–400 mesh) using a

petroleum ether–ethyl acetate mixture (4:1 v/v), which afforded the

pure compound.

Compound (II) was prepared by the same method using

4-chlorobenzaldehyde in place of 2-methylbenzaldehyde and with a

stirring time of 6 h.

Compound (I)

Crystal data

C₂₆H₁₈F₃N₃OS

M_r= 477.49

Triclinic, P1

ꢃ = 95.676 (2)^ꢂ

V = 1135.36 (9) A

Z = 2

Mo Kꢁ radiation

ꢄ = 0.19 mm^ꢁ1

T = 298 K

0.28 ꢄ 0.18 ꢄ 0.12 mm

3

˚

a = 10.0323 (4) A

Figure 5

b = 10.3715 (5) A

A layer of molecules of (I) with C—Hꢀ ꢀ ꢀO, C—Hꢀ ꢀ ꢀꢀ and ꢀ–ꢀ

interactions between them. Nonparticipating H atoms, methyl C atoms,

thiophene rings and the minor component of the disordered thiophene

and –CF₃groups have been omitted for clarity. The corresponding ﬁgure

for (II) is identical to that of (I).

˚

c = 11.7411 (5) A

ꢁ = 109.211 (2)^ꢂ

ꢂ = 96.105 (2)^ꢂ

Data collection

Bruker APEXII CCD

diffractometer

Absorption correction: multi-scan

(SADABS; Bruker, 2009)

T_min= 0.900, T_max= 0.989

25018 measured reﬂections

6692 independent reﬂections

4773 reﬂections with I > 2ꢅ(I)

R_int= 0.025

carefully. Further, a C22—H22ꢀ ꢀ ꢀCg2ⁱⁱⁱinteraction, with

Hꢀ ꢀ ꢀCg2ⁱⁱⁱdistances [symmetry code: (iii) ꢁx + 1, ꢁy + 1, ꢁz]

˚

of 2.76 and 2.74 A in (I) and (II), respectively, links these

chains into sheets parallel to the bc plane and may well be

regarded as the weakest interaction and yet is crucial in the

crystal structure. Thus, the structures of (I) and (II) serve as

good examples of the importance of C—Hꢀ ꢀ ꢀꢀ and ꢀ–ꢀ

interactions amidst extensive disorder in molecules in the

crystalline state.

Reﬁnement

R[F²> 2ꢅ(F²)] = 0.045

wR(F²) = 0.126

S = 1.02

6692 reﬂections

382 parameters

345 restraints

H-atom paramete_ꢁrs₃constrained

˚

Áꢆ_max= 0.19 e A

ꢁ3

˚

Áꢆ_min= ꢁ0.25 e A

Experimental

Compound (II)

For the preparation of compound (I), a mixture of 4,4,4-triﬂuoro-

1-(thiophen-2-yl)butane-1,3-dione (1 mmol), 2-methylbenzaldehyde

(1 mmol) and 3-methyl-1-phenyl-1H-pyrazol-5-amine (1 mmol) in

the presence of l-proline (50 mol%) in ethanol (15 ml) was stirred at

333 K for 7 h. After completion of the reaction [monitored by thin-

layer chromatography (TLC)], the reaction mixture was extracted

Crystal data

C₂₅H₁₅ClF₃N₃OS

M_r= 497.91

Triclinic, P1

ꢃ = 95.628 (4)^ꢂ

V = 1125.82 (15) A

Z = 2

Mo Kꢁ radiation

ꢄ = 0.31 mm^ꢁ1

T = 298 K

3

˚

a = 10.0018 (7) A

˚

b = 10.3503 (8) A

˚

c = 11.6309 (10) A

ꢁ = 108.607 (4)^ꢂ

ꢂ = 95.295 (4)^ꢂ

0.30 ꢄ 0.14 ꢄ 0.12 mm

Table 1

Hydrogen-bond geometry (A, ) for (I).

ꢂ

˚

Data collection

Cg2 is the centroid of the C12–C17 ring.

Bruker APEXII CCD

diffractometer

Absorption correction: multi-scan

(SADABS; Bruker, 2009)

T_min= 0.890, T_max= 0.978

22298 measured reﬂections

5407 independent reﬂections

3912 reﬂections with I > 2ꢅ(I)

R_int= 0.027

D—Hꢀ ꢀ ꢀA

D—H

Hꢀ ꢀ ꢀA

Dꢀ ꢀ ꢀA

D—Hꢀ ꢀ ꢀA

C15—H15ꢀ ꢀ ꢀO1ⁱ

C20—H20ꢀ ꢀ ꢀO1ⁱⁱ

C22—H22ꢀ ꢀ ꢀCg2ⁱⁱⁱ

0.93

2.66

2.65

2.76

3.531 (2)

3.2769 (18)

3.4509 (17)

156

126

132

Reﬁnement

Symmetry codes: (i) x; y ꢁ 1; z ꢁ 1; (ii) ꢁx þ 1; ꢁy þ 1; ꢁz þ 1; (iii) ꢁx þ 1; ꢁy þ 1,

R[F²> 2ꢅ(F²)] = 0.037

wR(F²) = 0.097

S = 1.03

5407 reﬂections

382 parameters

345 restraints

H-atom paramete_ꢁrs₃constrained

ꢁz.

˚

Áꢆ_max= 0.21 e A

Áꢆ_min= ꢁ0.19 e A

Table 2

Hydrogen-bond geometry (A, ) for (II).

ꢁ3

˚

ꢂ

˚

Cg2 is the centroid of the C12–C17 ring.

The structures were reﬁned against F²on all data by full-matrix

least-squares with SHELXL97 (Sheldrick, 2008), following estab-

¨

lished reﬁnement strategies (Muller, 2009). All H atoms were

included in the model at geometrically calculated positions (C—H

D—Hꢀ ꢀ ꢀA

D—H

Hꢀ ꢀ ꢀA

Dꢀ ꢀ ꢀA

D—Hꢀ ꢀ ꢀA

C15—H15ꢀ ꢀ ꢀO1ⁱ

C20—H20ꢀ ꢀ ꢀO1ⁱⁱ

C22—H22ꢀ ꢀ ꢀCg2ⁱⁱⁱ

0.93

2.74

2.57

2.74

3.610 (2)

3.209 (2)

3.4075 (18)

156

127

129

˚

target distance = 0.96 A for methyl H atoms and 0.93 A for all others)

and reﬁned using a riding model. Except for one methyl group

Symmetry codes: (i) x; y ꢁ 1; z ꢁ 1; (ii) ꢁx þ 1; ꢁy þ 1; ꢁz þ 2; (iii) ꢁx þ 1; ꢁy þ 1,

ꢁz þ 1.

ꢃ

414 Rajni Swamy et al.

C₂₆H₁₈F₃N₃OS and C₂₅H₁₅ClF₃N₃OS

Acta Cryst. (2013). C69, 412–415

organic compounds

(deﬁned by C26), which was reﬁned as disordered (see below), the

torsion angles of the methyl groups were allowed to reﬁne. The U_iso

values of all H atoms were constrained to 1.2 times U_eq(1.5 times for

methyl H atoms) of the respective atom to which the H atom binds.

As mentioned above, both structures display disorder of the –CF₃

and thiophene groups. This disorder was treated identically in both

structures and this reﬁnement is explained only once (the atom

names are the same in both structures, see Figs. 1 and 2). Disorder

was reﬁned with the help of similarity restraints on 1–2 and 1–3

distances and displacement parameters, as well as rigid bond

restraints (viz. Hirshfeld restraints) for anisotropic displacement

parameters.

restraints mentioned above, the thiophene rings were restrained to be

approximately planar, yet no coplanarity of the disorder components

was assumed. The occupancy ratios of the two components were

reﬁned freely and converged at 0.845 (2) for (I) and at 0.860 (2) for

(II).

In addition to the disorder described above, the methyl group

deﬁned by C26 in (I) was reﬁned as rotating about the C21—C26

bond with six half-occupied H atoms 60^ꢂapart. This disorder was

introduced because there was signiﬁcant residual electron density

between the three H atoms of this methyl group when the torsion

angle of this methyl group was reﬁned. Introducing this third disor-

dered assembly in (I) further improves the model signiﬁcantly.

Both data sets contain reﬂections partially obscured by the

primary beam stop [one reﬂection for the data of (I) and three

reﬂections for the data of (II)]. These reﬂections were omitted from

the reﬁnements.

The ﬁrst approach to the –CF₃disorder was to reﬁne the –CF₃

group as freely rotating about the C5—C25 bond [typical similarity

restraints and equal anisotropic displacement constraints for this

¨

model are explained in detail in Muller (2009)]. While this approach

was partially successful, the displacement ellipsoids of the six F atoms

do not form a circular toroid as expected for a pure rotation about the

C—C bond, but rather an oval elongated in a direction approximately

perpendicular to the aromatic ring plane to which the –CF₃group

binds. In addition, there is still appreciable residual electron density

around the –CF₃group and the displacement ellipsoid of C25, the C

atom in the –CF₃group carrying the F atoms, is elongated in a

direction perpendicular to the plane of the aromatic system to which

the –CF₃group binds. Therefore, the position of C25 was split as well,

thus describing the –CF₃group as being slightly above or below the

aromatic system to which it is bound. This approach does not require

the use of constraints and gives rise to an improved model. Even

though the anisotropic displacement ellipsoids of C25 and C25A are

still elongated, the residual electron density is much lower and the

residual values of the reﬁnement are signiﬁcantly better. It should be

noted that in the ﬁrst model, Hirshfeld restraints applied to the six

C25—F bonds (unsuccessfully) pushed the ellipsoid of atom C25 to

be almost perfectly round. This effect is much weaker in the second

model, which may explain why the ellipsoids for C25 and C25A are

still elongated. This elongation should not be considered a problem,

however, as the displacement ellipsoids of C25 and C25A are elon-

gated along the direction of the motion suggested in the disorder

model (the entire –CF₃group is moving slightly up and down

perpendicular to the aromatic plane while rotating). The occupancy

ratios of the two components were reﬁned freely and converged at

0.569 (7) for (I) and at 0.577 (9) for (II).

For both compounds, data collection: APEX2 (Bruker, 2009); cell

reﬁnement: SAINT (Bruker, 2009); data reduction: SAINT;

program(s) used to solve structure: SHELXS97 (Sheldrick, 2008);

program(s) used to reﬁne structure: SHELXL97 (Sheldrick, 2008);

molecular graphics: PLATON (Spek, 2009); software used to prepare

material for publication: SHELXL97.

The authors thank the Sophisticated Analytical Instru-

mentation Facility (SAIF), Indian Institute of Technology,

Chennai, for the X-ray intensity data collection.

Supplementary data for this paper are available from the IUCr electronic

archives (Reference: TP3020). Services for accessing these data are

described at the back of the journal.

References

Allen, F . H . (2002). Acta Cryst. B 58 , 380–388.

Bruker (2009). APEX2 . Bruker AXS Inc., Madison, Wisconsin, USA.

Desiraju, G. R. & Sarma, J. A. R. P . (1986). Proc. Indian Acad. Sci. Chem. Sci.

96 , 599–605.

Gnanaguru, K., Murthy, G. S., Venkatesan, K. & Ramamurthy, V . (1984).

Chem. Phys. Lett. 109 , 255–258.

Jones, W., Ramdas, S., Theocharis, C. R., Thomas, J. M. & Thomas, N. W.

(1981). J. Phys. Chem. 85 , 2594–2597.

Kitaigorodskii, A. I. (1973). In Molecular Crystals and Molecules . New York:

Academic Press.

M u ¨l ler, P . (2009). Crystallogr. Rev. 15 , 57–83.

Both structures show disorder of the thiophene ring, corre-

sponding to an approximate 180^ꢂrotation about the C7—C8 bond,

leading the ring systems of the two disorder components to be

approximately coplanar. In addition to the types of similarity

Schmidt, G. M. J. (1971). Pure Appl. Chem. 27 , 647–678.

Sheldrick, G. M. (2008). Acta Cryst. A 64 , 112–122.

Spek, A. L. (2009). Acta Cryst. D 65 , 148–155.

ꢃ

Acta Cryst. (2013). C69, 412–415

Rajni Swamy et al.

C₂₆H₁₈F₃N₃OS and C₂₅H₁₅ClF₃N₃OS 415

supplementary materials

Acta Cryst. (2013). C69, 412-415 [doi:10.1107/S0108270113004812]

Isomorphous methyl- and chloro-substituted small heterocyclic analogues

obeying the chlorine–methyl (Cl–Me) exchange rule

V. Rajni Swamy, P. Müller, N. Srinivasan, S. Perumal and R. V. Krishnakumar

(I) [3-Methyl-4-(4-methylphenyl)-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-

yl)methanone

Crystal data

C₂₆H₁₈F₃N₃OS

Z = 2

M_r= 477.49

Triclinic, P1

F(000) = 492

D_x= 1.397 Mg m⁻³

Mo Kα radiation, λ = 0.71073 Å

Cell parameters from 10124 reflections

θ = 2.1–28.0°

Hall symbol: -P 1

a = 10.0323 (4) Å

b = 10.3715 (5) Å

c = 11.7411 (5) Å

α = 109.211 (2)°

β = 96.105 (2)°

γ = 95.676 (2)°

V = 1135.36 (9) Å³

µ = 0.19 mm⁻¹

T = 298 K

Needle, yellow

0.28 × 0.18 × 0.12 mm

Data collection

Bruker APEXII CCD

diffractometer

Radiation source: fine-focus sealed tube

Graphite monochromator

ω and φ scans

25018 measured reflections

6692 independent reflections

4773 reflections with I > 2σ(I)

R_int= 0.025

θ

_max= 30.4°, θ_min= 2.1°

Absorption correction: multi-scan

(SADABS; Bruker, 2009)

h = −14→13

k = −14→14

l = −16→16

T

_min= 0.900, T_max= 0.989

Refinement

Refinement on F²

Least-squares matrix: full

R[F²> 2σ(F²)] = 0.045

wR(F²) = 0.126

Secondary atom site location: difference Fourier

map

Hydrogen site location: inferred from

neighbouring sites

S = 1.02

6692 reflections

382 parameters

345 restraints

Primary atom site location: structure-invariant

direct methods

H-atom parameters constrained

w = 1/[σ²(F_o²) + (0.055P)²+ 0.2446P]

where P = (F_o²+ 2F_c²)/3

(Δ/σ)_max< 0.001

Δρ_max= 0.19 e Å⁻³

Δρ_min= −0.25 e Å⁻³

Acta Cryst. (2013). C69, 412-415

sup-1

supplementary materials

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full

covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and

torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry.

An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F²against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F²,

conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F²> σ(F²) is used

only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F²

are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²)

x

y

z

U_iso*/U_eq

Occ. (<1)

O1

0.22031 (13)

0.45272 (11)

0.57941 (12)

0.24775 (11)

0.58186 (13)

0.45472 (12)

0.39830 (13)

0.26395 (13)

0.19596 (13)

0.0502 (6)

−0.0332 (3)

0.0218 (5)

0.0284 (4)

0.0600 (8)

0.0660 (5)

−0.0196 (6)

−0.0148 (6)

0.37445 (13)

0.19828 (13)

0.11091 (13)

0.00886 (7)

−0.0533 (5)

−0.1191

0.53727 (13)

0.20561 (11)

0.28107 (12)

0.23106 (11)

0.39452 (14)

0.39688 (12)

0.48555 (12)

0.44530 (13)

0.31823 (14)

0.2683 (7)

0.3069 (8)

0.3180 (6)

0.1350 (3)

0.2512 (9)

0.1633 (9)

0.1901 (10)

0.3372 (5)

0.27416 (13)

0.53776 (14)

0.62838 (14)

0.71013 (8)

0.7880 (5)

0.8461

0.43932 (10)

−0.02588 (10)

−0.00452 (11)

0.06404 (10)

0.08892 (12)

0.13287 (11)

0.22745 (11)

0.23546 (12)

0.15358 (12)

0.1625 (6)

0.0918 (5)

0.2697 (3)

0.1241 (7)

0.1634 (7)

0.2197 (9)

0.0643 (4)

0.2272 (9)

0.05595 (11)

0.33622 (12)

0.30385 (12)

0.40507 (6)

0.3084 (4)

0.3248

0.0649 (3)

0.0423 (3)

0.0469 (3)

0.0438 (3)

0.0436 (3)

0.0376 (3)

0.0368 (3)

0.0401 (3)

0.0436 (3)

0.0624 (15)

0.1235 (18)

0.1110 (19)

0.132 (3)

0.0580 (18)

0.133 (3)

0.125 (3)

0.129 (3)

0.0383 (3)

0.0431 (3)

0.0423 (3)

0.05390 (18)

0.0586 (7)

0.070*

N1

N2

N3

C1

C2

C3

C4

C5

C25

F1

0.569 (7)

0.431 (7)

F2

F3

C25A

F1A

F2A

F3A

C6

C7

C8

S1

0.845 (2)

0.155 (2)

C9

H9

C10

H10

C11

H11

S1A

C9A

H9A

C10A

H10A

C11A

H11A

C12

C13

H13

0.0032 (6)

−0.0168

0.7563 (7)

0.7917

0.2051 (5)

0.1431

0.0626 (9)

0.075*

0.0958 (6)

0.1426

0.6631 (6)

0.6285

0.2031 (3)

0.1378

0.0589 (9)

0.071*

0.1045 (8)

−0.012 (3)

−0.0535

0.6501 (9)

0.761 (3)

0.1657 (5)

0.203 (3)

0.0652 (13)

0.064 (3)

0.077*

0.8001

0.1510

−0.036 (3)

−0.0898

0.783 (3)

0.318 (3)

0.074 (4)

0.089*

0.8463

0.3581

0.0292 (16)

0.0163

0.7016 (18)

0.6982

0.3688 (14)

0.4451

0.064 (3)

0.077*

0.42500 (14)

0.29410 (17)

0.2222

0.07335 (13)

0.01699 (15)

0.0638

−0.11801 (11)

−0.17233 (14)

−0.1471

0.0420 (3)

0.0551 (4)

0.066*

Acta Cryst. (2013). C69, 412-415

sup-2

supplementary materials

C14

0.2707 (2)

0.1825

−0.11019 (17)

−0.1488

−0.26499 (16)

−0.3020

0.0665 (5)

0.080*

H14

C15

0.3765 (2)

0.3603

−0.17989 (16)

−0.2645

−0.30278 (15)

−0.3660

0.0665 (5)

0.080*

H15

C16

0.5059 (2)

0.5773

−0.12383 (16)

−0.1716

−0.24672 (14)

−0.2716

0.0606 (4)

0.073*

H16

C17

0.53208 (17)

0.6202

0.00274 (15)

0.0398

−0.15371 (13)

−0.1158

0.0502 (3)

0.060*

H17

C18

0.48269 (13)

0.57813 (15)

0.5852

0.61143 (12)

0.59816 (14)

0.5115

0.31676 (11)

0.40508 (12)

0.4104

0.0370 (3)

0.0459 (3)

0.055*

C19

H19

C20

0.66267 (15)

0.7261

0.71197 (14)

0.7010

0.48505 (13)

0.5437

0.0477 (3)

0.057*

H20

C21

0.65478 (14)

0.55912 (16)

0.5521

0.84204 (14)

0.85475 (14)

0.9416

0.47957 (13)

0.39198 (13)

0.3871

0.0454 (3)

0.0488 (3)

0.059*

C22

H22

C23

0.47327 (15)

0.4092

0.74156 (13)

0.7529

0.31123 (13)

0.2532

0.0447 (3)

0.054*

H23

C24

0.70538 (16)

0.7675

0.49990 (18)

0.4777

0.13200 (16)

0.0739

0.0614 (4)

0.092*

H24A

H24B

H24C

C26

0.7477

0.5006

0.2095

0.092*

0.6805

0.5892

0.1403

0.092*

0.74974 (18)

0.8087

0.96556 (17)

0.9370

0.56560 (17)

0.6198

0.0671 (5)

H26A

H26B

H26C

H26D

H26E

H26F

0.101*

0.50

0.6982

1.0319

0.6121

0.8028

1.0065

0.5196

0.7311

1.0466

0.5479

0.8416

0.9517

0.5556

0.7370

0.9771

0.6481

Atomic displacement parameters (Å²)

U¹¹

U²²

U³³

U¹²

U¹³

U²³

O1

0.0818 (8)

0.0433 (6)

0.0434 (6)

0.0417 (6)

0.0422 (6)

0.0399 (6)

0.0434 (6)

0.0414 (6)

0.0393 (6)

0.037 (2)

0.0400 (11)

0.091 (3)

0.084 (3)

0.053 (3)

0.073 (2)

0.070 (3)

0.0745 (8)

0.0362 (6)

0.0457 (6)

0.0390 (6)

0.0417 (7)

0.0324 (6)

0.0307 (6)

0.0378 (6)

0.0443 (7)

0.051 (2)

0.197 (5)

0.135 (3)

0.0425 (15)

0.072 (5)

0.155 (5)

0.187 (8)

0.0431 (6)

0.0394 (6)

0.0437 (6)

0.0431 (6)

0.0412 (7)

0.0371 (6)

0.0346 (6)

0.0378 (6)

0.0422 (7)

0.070 (3)

0.130 (3)

0.0646 (15)

0.227 (6)

0.048 (3)

0.231 (7)

0.070 (2)

0.0340 (6)

0.0070 (4)

0.0061 (5)

0.0055 (4)

0.0068 (5)

0.0071 (5)

0.0098 (5)

0.0113 (5)

0.0079 (5)

−0.0051 (17)

0.0192 (19)

−0.050 (2)

−0.0171 (13)

0.017 (3)

0.0136 (5)

0.0184 (5)

0.0017 (4)

0.0043 (5)

0.0044 (5)

0.0063 (6)

0.0072 (5)

0.0081 (5)

0.0071 (5)

0.0078 (6)

−0.014 (2)

0.054 (3)

N1

0.0074 (4)

0.0088 (5)

0.0048 (5)

0.0063 (5)

0.0050 (5)

0.0042 (5)

0.0055 (5)

0.0057 (5)

0.0084 (19)

0.0018 (15)

0.0421 (15)

0.076 (4)

N2

N3

C1

C2

C3

C4

C5

C25

F1

F2

−0.0126 (15)

−0.018 (2)

0.014 (3)

F3

C25A

F1A

F2A

0.018 (2)

0.007 (3)

0.034 (3)

0.144 (5)

−0.054 (4)

0.0078 (16)

0.000 (3)

Acta Cryst. (2013). C69, 412-415

sup-3

supplementary materials

F3A

C6

0.064 (3)

0.058 (2)

0.225 (7)

0.0022 (16)

0.0103 (5)

0.0089 (5)

0.0090 (5)

0.0188 (2)

0.0218 (11)

0.0234 (14)

0.0214 (11)

0.0340 (18)

0.028 (5)

0.076 (4)

−0.020 (3)

0.0054 (5)

0.0069 (5)

0.0047 (5)

0.0095 (3)

0.0140 (12)

0.0246 (13)

0.0138 (17)

0.027 (3)

0.0417 (6)

0.0435 (7)

0.0389 (6)

0.0491 (3)

0.0450 (15)

0.059 (2)

0.0338 (6)

0.0422 (7)

0.0419 (7)

0.0574 (3)

0.0563 (14)

0.0703 (19)

0.0662 (16)

0.081 (3)

0.0354 (6)

0.0392 (7)

0.0402 (7)

0.0532 (3)

0.0718 (16)

0.0619 (14)

0.0500 (19)

0.060 (3)

0.0046 (5)

0.0075 (5)

0.0079 (5)

0.0195 (2)

0.0097 (12)

0.0057 (13)

0.0140 (15)

0.011 (2)

C7

C8

S1

C9

C10

C11

S1A

C9A

C10A

C11A

C12

C13

C14

C15

C16

C17

C18

C19

C20

C21

C22

C23

C24

C26

0.0599 (15)

0.062 (2)

0.044 (6)

0.058 (7)

0.089 (7)

0.006 (6)

0.019 (6)

0.053 (7)

0.069 (7)

0.084 (6)

0.026 (5)

0.005 (5)

0.000 (6)

0.056 (6)

0.063 (6)

0.066 (6)

0.015 (4)

0.021 (5)

0.005 (5)

0.0571 (8)

0.0578 (9)

0.0796 (12)

0.1101 (15)

0.0974 (13)

0.0648 (9)

0.0431 (6)

0.0577 (8)

0.0510 (7)

0.0474 (7)

0.0629 (9)

0.0540 (8)

0.0469 (8)

0.0645 (10)

0.0333 (6)

0.0455 (8)

0.0485 (9)

0.0331 (7)

0.0447 (8)

0.0473 (8)

0.0309 (6)

0.0319 (6)

0.0434 (7)

0.0386 (7)

0.0305 (6)

0.0371 (7)

0.0621 (10)

0.0500 (9)

0.0335 (6)

0.0509 (8)

0.0542 (9)

0.0490 (9)

0.0466 (8)

0.0405 (7)

0.0346 (6)

0.0439 (7)

0.0413 (7)

0.0422 (7)

0.0516 (8)

0.0424 (7)

0.0588 (9)

0.0660 (11)

0.0109 (5)

0.0054 (6)

−0.0112 (8)

0.0069 (8)

0.0328 (8)

0.0220 (7)

0.0079 (5)

0.0113 (6)

0.0101 (6)

0.0020 (5)

0.0041 (6)

0.0077 (6)

−0.0044 (7)

−0.0093 (7)

0.0091 (5)

0.0099 (7)

0.0098 (8)

0.0196 (9)

0.0240 (8)

0.0118 (6)

0.0088 (5)

0.0002 (6)

−0.0014 (6)

0.0113 (6)

0.0099 (7)

0.0029 (6)

0.0119 (7)

0.0033 (8)

0.0068 (5)

0.0018 (7)

0.0005 (7)

0.0031 (6)

0.0144 (7)

0.0123 (6)

0.0062 (5)

0.0082 (5)

0.0062 (6)

0.0032 (6)

0.0124 (6)

0.0137 (6)

0.0013 (8)

−0.0007 (8)

Geometric parameters (Å, º)

O1—C7

N1—C6

N1—N2

N1—C12

N2—C1

N3—C6

N3—C5

C1—C2

C1—C24

C2—C3

C2—C6

C3—C4

C3—C18

C4—C5

C4—C7

C5—C25A

C5—C25

C25—F2

C25—F3

C25—F1

C25A—F2A

1.2090 (17)

C9A—H9A

0.9300

1.3662 (15)

1.3773 (16)

1.4188 (16)

1.3145 (17)

1.3288 (17)

1.3327 (16)

1.4254 (18)

1.490 (2)

C10A—C11A

C10A—H10A

C11A—H11A

C12—C13

C12—C17

C13—C14

C13—H13

C14—C15

C14—H14

C15—C16

C15—H15

C16—C17

C16—H16

C17—H17

C18—C23

C18—C19

C19—C20

C19—H19

C20—C21

C20—H20

1.360 (18)

0.9300

1.378 (2)

1.3840 (19)

1.385 (2)

0.9300

1.374 (3)

0.9300

1.4014 (16)

1.4036 (17)

1.3933 (18)

1.4874 (17)

1.4055 (19)

1.5157 (17)

1.502 (8)

1.369 (3)

0.9300

1.383 (2)

0.9300

1.3843 (18)

1.3857 (18)

1.3775 (19)

0.9300

1.529 (6)

1.268 (7)

1.293 (7)

1.298 (7)

1.381 (2)

0.9300

1.270 (8)

Acta Cryst. (2013). C69, 412-415

sup-4

supplementary materials

C25A—F1A

C25A—F3A

C7—C8

1.293 (9)

1.316 (9)

1.4572 (19)

1.306 (12)

1.344 (4)

1.705 (6)

1.7166 (13)

1.698 (3)

1.349 (4)

0.9300

C21—C22

1.378 (2)

1.507 (2)

1.3830 (19)

0.9300

0.9600

C21—C26

C22—C23

C8—C11A

C8—C11

C8—S1A

C8—S1

C22—H22

C23—H23

C24—H24A

C24—H24B

C24—H24C

C26—H26A

C26—H26B

C26—H26C

C26—H26D

C26—H26E

C26—H26F

S1—C9

C9—C10

C9—H9

C10—C11

C10—H10

C11—H11

S1A—C9A

C9A—C10A

1.402 (6)

0.9300

0.9600

1.706 (19)

1.344 (17)

C6—N1—N2

C6—N1—C12

N2—N1—C12

C1—N2—N1

C6—N3—C5

110.02 (10)

130.48 (11)

119.38 (10)

107.65 (11)

114.01 (11)

110.33 (12)

120.30 (12)

129.36 (12)

118.43 (12)

136.61 (12)

104.96 (11)

116.51 (11)

123.14 (11)

120.27 (11)

119.12 (11)

118.53 (11)

122.29 (12)

125.57 (12)

109.0 (4)

C8—C11A—H11A

122.0

C10A—C11A—H11A

C13—C12—C17

C13—C12—N1

C17—C12—N1

C12—C13—C14

C12—C13—H13

C14—C13—H13

C15—C14—C13

C15—C14—H14

C13—C14—H14

C16—C15—C14

C16—C15—H15

C14—C15—H15

C15—C16—C17

C15—C16—H16

C17—C16—H16

C16—C17—C12

C16—C17—H17

C12—C17—H17

C23—C18—C19

C23—C18—C3

C19—C18—C3

C20—C19—C18

C20—C19—H19

C18—C19—H19

C19—C20—C21

C19—C20—H20

C21—C20—H20

C22—C21—C20

C22—C21—C26

C20—C21—C26

C21—C22—C23

122.0

120.52 (13)

120.67 (12)

118.81 (13)

119.32 (15)

120.3

N2—C1—C2

N2—C1—C24

C2—C1—C24

C3—C2—C6

120.3

120.63 (17)

119.7

C3—C2—C1

C6—C2—C1

119.7

C4—C3—C2

119.48 (14)

120.3

C4—C3—C18

C2—C3—C18

C3—C4—C5

120.3

121.10 (15)

119.5

C3—C4—C7

C5—C4—C7

119.5

N3—C5—C4

N3—C5—C25A

C4—C5—C25A

N3—C5—C25

C4—C5—C25

F2—C25—F3

F2—C25—F1

F3—C25—F1

F2—C25—C5

F3—C25—C5

F1—C25—C5

F2A—C25A—F1A

F2A—C25A—F3A

F1A—C25A—F3A

F2A—C25A—C5

F1A—C25A—C5

118.93 (16)

120.5

125.0 (3)

120.5

113.8 (3)

118.63 (12)

122.02 (11)

119.28 (11)

120.67 (12)

119.7

120.6 (3)

110.8 (6)

107.1 (6)

106.6 (5)

112.3 (4)

119.7

110.1 (5)

121.11 (13)

119.4

109.7 (5)

106.1 (8)

119.4

101.9 (7)

117.98 (12)

121.25 (14)

120.76 (14)

121.62 (13)

102.2 (6)

116.6 (6)

114.0 (6)

Acta Cryst. (2013). C69, 412-415

sup-5

supplementary materials

F3A—C25A—C5

N3—C6—N1

114.3 (7)

126.63 (11)

126.30 (11)

107.04 (11)

121.97 (12)

120.76 (12)

117.25 (12)

101.5 (8)

128.4 (7)

130.1 (2)

110.5 (7)

121.2 (2)

110.73 (19)

119.16 (11)

119.6 (2)

91.27 (14)

112.5 (3)

123.7

C21—C22—H22

C23—C22—H22

C22—C23—C18

C22—C23—H23

C18—C23—H23

C1—C24—H24A

C1—C24—H24B

119.2

N3—C6—C2

119.99 (13)

120.0

N1—C6—C2

O1—C7—C8

120.0

O1—C7—C4

109.5

C8—C7—C4

109.5

C11A—C8—C11

C11A—C8—C7

C11—C8—C7

H24A—C24—H24B

C1—C24—H24C

109.5

141.1

56.3

H24A—C24—H24C

H24B—C24—H24C

C21—C26—H26A

C21—C26—H26B

H26A—C26—H26B

C21—C26—H26C

H26A—C26—H26C

H26B—C26—H26C

C21—C26—H26D

H26A—C26—H26D

H26B—C26—H26D

H26C—C26—H26D

C21—C26—H26E

H26A—C26—H26E

H26B—C26—H26E

H26C—C26—H26E

H26D—C26—H26E

C21—C26—H26F

H26A—C26—H26F

H26B—C26—H26F

H26C—C26—H26F

H26D—C26—H26F

H26E—C26—H26F

C11A—C8—S1A

C7—C8—S1A

C11—C8—S1

C7—C8—S1

S1A—C8—S1

C9—S1—C8

C10—C9—S1

C10—C9—H9

S1—C9—H9

123.7

C9—C10—C11

C9—C10—H10

C11—C10—H10

C8—C11—C10

C8—C11—H11

C10—C11—H11

C8—S1A—C9A

C10A—C9A—S1A

C10A—C9A—H9A

S1A—C9A—H9A

C9A—C10A—C11A

C9A—C10A—H10A

C11A—C10A—H10A

C8—C11A—C10A

111.5 (3)

124.3

56.3

124.3

109.5

56.3

114.0 (3)

123.0

141.1

56.3

123.0

90.6 (9)

109.5

56.3

111.3 (17)

124.4

56.3

111.3 (19)

124.3

141.1

109.5

124.3

116.0 (14)

Hydrogen-bond geometry (Å, º)

Cg2 is the centroid of the C12–C17 ring.

D—H···A

D—H

H···A

D···A

D—H···A

C15—H15···O1ⁱ

C20—H20···O1ⁱⁱ

C22—H22···Cg2ⁱⁱⁱ

0.93

2.66

2.65

2.76

3.531 (2)

156

126

132

3.2769 (18)

3.4509 (17)

Symmetry codes: (i) x, y−1, z−1; (ii) −x+1, −y+1, −z+1; (iii) −x+1, −y+1, −z.

(II) [4-(4-Chlorophenyl)-3-methyl-1-phenyl-6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridin-5-yl](thiophen-2-

yl)methanone

Crystal data

C₂₅H₁₅ClF₃N₃OS

Triclinic, P1

M_r= 497.91

Hall symbol: -P 1

Acta Cryst. (2013). C69, 412-415

sup-6

supplementary materials

a = 10.0018 (7) Å

b = 10.3503 (8) Å

c = 11.6309 (10) Å

α = 108.607 (4)°

β = 95.295 (4)°

γ = 95.628 (4)°

V = 1125.82 (15) Å³

Z = 2

D_x= 1.469 Mg m⁻³

Mo Kα radiation, λ = 0.71073 Å

Cell parameters from 1226 reflections

θ = 2.3–28.0°

µ = 0.31 mm⁻¹

T = 298 K

Needle, yellow

0.30 × 0.14 × 0.12 mm

F(000) = 508

Data collection

Bruker APEXII CCD

diffractometer

Radiation source: fine-focus sealed tube

Graphite monochromator

ω and φ scans

22298 measured reflections

5407 independent reflections

3912 reflections with I > 2σ(I)

R_int= 0.027

θ

_max= 28.1°, θ_min= 2.3°

Absorption correction: multi-scan

(SADABS; Bruker, 2009)

h = −13→13

k = −13→13

l = −15→15

T

_min= 0.890, T_max= 0.978

Refinement

Refinement on F²

Least-squares matrix: full

R[F²> 2σ(F²)] = 0.037

wR(F²) = 0.097

Secondary atom site location: difference Fourier

map

Hydrogen site location: inferred from

neighbouring sites

S = 1.03

5407 reflections

382 parameters

345 restraints

Primary atom site location: structure-invariant

direct methods

H-atom parameters constrained

w = 1/[σ²(F_o²) + (0.0372P)²+ 0.2614P]

where P = (F_o²+ 2F_c²)/3

(Δ/σ)_max< 0.001

Δρ_max= 0.21 e Å⁻³

Δρ_min= −0.19 e Å⁻³