1,3-Bis(2-cyanopropan-2-yl)-5-methyl­benzene

Gomathi, S.; Sathya, U.; Sharmila Tagore, S.; Nirmal Ram, J.S.; Manikandan, D.; Sethuraman, V.; McMillen, C.

doi:10.1107/S2414314619003766

organic compounds

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ISSN: 2414-3146

Volume 4| Part 4| April 2019| x190376

https://doi.org/10.1107/S2414314619003766

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1,3-Bis(2-cyanopropan-2-yl)-5-methylbenzene

Sundaramoorthy Gomathi,^a ^* Udhayasuriyan Sathya,^a Sadasivam Sharmila Tagore,^a Jeyaraman Selvaraj Nirmal Ram,^b Devakumar Manikandan,^a Velusamy Sethuraman ^a and Colin McMillen ^c

^aDepartment of Chemistry, Periyar Maniammai Institute of Science and Technology, Thanjavur 613 403, Tamil Nadu, India, ^bDepartment of Chemistry, PRIST Deemed to be University, Thanjavur 613 403, Tamil Nadu, India, and ^cMolecular Structure Center, Department of Chemistry, Clemson University, 379 Hunter Laboratories, Clemson, SC 29634-0973, USA
^*Correspondence e-mail: gomathichemist@gmail.com

Edited by S. Parkin, University of Kentucky, USA (Received 15 January 2019; accepted 19 March 2019; online 5 April 2019)

The complete molecule of the title compound [systematic name: 2,2′-(5-methyl-1,3-phenylene)bis(2-methylpropanenitrile)] is generated by a crystallographic twofold axis, which leads to disorder of the H atoms on the methyl group attached to the benzene ring. The dihedral angle between the benzene ring and the nitrile group is 26.2 (2)°. In the crystal, pairs of weak C—H⋯π interactions link molecules into dimers. The molecule absorbs at 212 nm as a result of a π–π* transition.

Keywords: 1,3-di(dimethylcyanomethyl)-5-methylbenzene; spectroscopic studies; crystal structure; non-covalent interaction.

CCDC reference: 1904010

Structure description

Anastrazole (1,3-di-(dimethylcyanomethyl)-5-([1,2,4]triazolylmethyl) benzene) is an active pharmaceutical ingredient that is used as a drug in the treatment of postmenopausal endocrine-responsive breast cancer (Varelas et al., 2007 ; Geisler et al., 1996 ; Dowsett et al., 2001 ) and it has cytotoxic impact against breast, liver hepatocellular and glandular cancer cells. The title compound, 1,3-di(dimethylcyanomethyl)-5-methylbenzene (MCMB) is used as a starting material (Hsieh et al., 2008 ) for the synthesis of anastrazole we now describe its crystal structure.

The asymmetric unit of the title compound consists of half a molecule of MCMB, with the other half being generated by a crystallographic twofold rotation axis (symmetry operation −x, y, $[{3\over 2}]$ − z) (Fig. 1). Individual bond lengths and angles are unremarkable. The dihedral angle between the benzene ring and the carbonitrile moiety is 24.81 (16)°.

Figure 1
An ellipsoid plot (50% probability) of 1,3-di(dimethylcyanomethyl)-5-methylbenzene (MCMB). Symmetry code: (a) −x, y, $[{3\over 2}]$ − z.

Within the crystal, molecules are linked by C—H⋯π interactions, with a C—H⋯Cgⁱ [symmetry code: (i) $[{1\over 2}]$ − x, $[{1\over 2}]$ − y, 2 − z] distance d(C⋯π) of 3.708 (3) Å and a C—H⋯π angle of 158°. The interaction leads to the formation inversion dimers arranged in a two-dimensional supramolecular strand-like architecture, linked by C—H⋯π interactions, as shown in Fig. 2.

Figure 2
Inversion dimers linked by C—H⋯π bonds [symmetry code: (i) $[{1\over 2}]$ − x, 1/2 − y, 2 − z] forming supramolecular strands. H atoms apart from the one that interacts with the phenyl group have been omitted to enhance the clarity of the figure.

An electronic transition takes place in the region of 212 nm because of a π–π* transition of the C=C benzene and C≡N nitrile bonds of MCMB. The UV spectrum is shown in Fig. 3.

Figure 3
UV absorption spectrum of MCMB.

Synthesis and crystallization

The compound MCMB (0.056 mg, 0.25 mmol), obtained as a gift sample, was dissolved in hot methanol and stirred for half an hour. The resulting solution was allowed to cool and stored for slow evaporation. After a week, colorless prismatic crystals were harvested from the mother solution.

IR spectra: ν_max(cm⁻¹): (C=C) 1601, 1458, (Ar C—H) 2984, in-plane bending vibration 1001, 1293, out-of-plane bending vibration 707, 867, (C≡N) 2237, (sym and asym CH₃) 2874, 2942; ¹H NMR (500 MHz, DMSO) δ: 1.7 (s,12H), 2.3 (s, 3H), 7.3 (o, 2H), 7.4 (p, 1H).

Refinement

Crystal data, data collection, and structure refinement details are summarized in Table 1. The H atoms attached to C7 are disordered over two sets of sites..

Table 1
Experimental details

Crystal data
Chemical formula	C₁₅H₁₈N₂
M_r	226.31
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	298
a, b, c (Å)	13.821 (6), 13.138 (3), 9.473 (3)
β (°)	126.133 (8)
V (Å³)	1389.3 (8)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.06
Crystal size (mm)	0.52 × 0.24 × 0.13

Data collection
Diffractometer	Rigaku Mercury
Absorption correction	Multi-scan (CrystalClear; Rigaku, 2008 )
T_min, T_max	0.653, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	5988, 1261, 1012
R_int	0.043
(sin θ/λ)_max (Å⁻¹)	0.600

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.059, 0.168, 1.06
No. of reflections	1261
No. of parameters	82
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.14
Computer programs: CrystalClear (Rigaku, 2008), SHELXT2015 (Sheldrick, 2015a ), SHELXL2015 (Sheldrick, 2015b ), PLATON (Spek, 2009 ), Mercury (Macrae et al., 2008 ), POVRay (Cason, 2004 ), PLATON (Spek, 2009) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 1904010

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314619003766/pk4023sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314619003766/pk4023Isup2.hkl

Spectroscopic information. DOI: https://doi.org/10.1107/S2414314619003766/pk4023sup3.doc

Supporting information file. DOI: https://doi.org/10.1107/S2414314619003766/pk4023Isup4.cml

checkCIF report

Computing details top

Data collection: CrystalClear (Rigaku, 2008); cell refinement: CrystalClear (Rigaku, 2008); data reduction: CrystalClear (Rigaku, 2008); program(s) used to solve structure: SHELXT2015 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2015 (Sheldrick, 2015b); molecular graphics: PLATON (Spek, 2009), Mercury (Macrae et al., 2008) and POVRay (Cason, 2004); software used to prepare material for publication: PLATON (Spek, 2009) and publCIF (Westrip, 2010).

2,2'-(5-Methyl-1,3-phenylene)bis(2-methylpropanenitrile) top

Crystal data top

C₁₅H₁₈N₂	F(000) = 488
M_r = 226.31	D_x = 1.082 Mg m⁻³
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 1261 reflections
a = 13.821 (6) Å	θ = 2.4–25.2°
b = 13.138 (3) Å	µ = 0.06 mm⁻¹
c = 9.473 (3) Å	T = 298 K
β = 126.133 (8)°	Prism, colourless
V = 1389.3 (8) Å³	0.52 × 0.24 × 0.13 mm
Z = 4

Data collection top

Rigaku Mercury diffractometer	1261 independent reflections
Radiation source: Sealed Tube	1012 reflections with I > 2σ(I)
Graphite Monochromator monochromator	R_int = 0.043
Detector resolution: 18.4 pixels mm^-1	θ_max = 25.3°, θ_min = 2.4°
dtprofit.ref scans	h = −14→16
Absorption correction: multi-scan (CrystalClear; Rigaku, 2008)	k = −15→15
T_min = 0.653, T_max = 1.000	l = −11→11
5988 measured reflections

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.059	H-atom parameters constrained
wR(F²) = 0.168	w = 1/[σ²(F_o²) + (0.0857P)² + 0.652P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
1261 reflections	Δρ_max = 0.18 e Å⁻³
82 parameters	Δρ_min = −0.14 e Å⁻³

Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > 2sigma(F²) is used only for calculating -R-factor-obs 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.

All hydrogen atoms were positioned geometrically and were refined using a riding model with C—H bond lengths 0.93–0.96 Å and with U_iso(H) = 1.2Ueq(C) for CH (aromatic) or 1.5Ueq(C) for CH₃.

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
N10	0.2028 (3)	0.50771 (16)	0.8107 (5)	0.1065 (13)
C1	0.07549 (16)	0.16087 (13)	0.7249 (2)	0.0490 (6)
C2	0.07652 (15)	0.26634 (13)	0.7246 (2)	0.0427 (5)
C3	0.00000	0.31872 (17)	0.75000	0.0422 (7)
C4	0.00000	0.10686 (19)	0.75000	0.0527 (8)
C5	0.15448 (16)	0.32323 (13)	0.6845 (2)	0.0476 (6)
C6	0.1794 (2)	0.42686 (15)	0.7556 (3)	0.0646 (8)
C7	0.00000	−0.0085 (2)	0.75000	0.0781 (13)
C8	0.2775 (2)	0.27308 (17)	0.7686 (3)	0.0678 (8)
C9	0.0871 (2)	0.3299 (2)	0.4854 (3)	0.0848 (10)
H1	0.12620	0.12544	0.70811	0.0590*
H3	0.00000	0.38950	0.75000	0.0510*
H7A	−0.03430	−0.03284	0.80706	0.1170*	0.500
H7B	0.08078	−0.03284	0.81121	0.1170*	0.500
H7C	−0.04647	−0.03284	0.63173	0.1170*	0.500
H8A	0.32525	0.31468	0.74812	0.1020*
H8B	0.26704	0.20704	0.71796	0.1020*
H8C	0.31717	0.26621	0.89209	0.1020*
H9A	0.01218	0.36436	0.43489	0.1270*
H9B	0.07231	0.26250	0.43753	0.1270*
H9C	0.13464	0.36694	0.45929	0.1270*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N10	0.128 (2)	0.0523 (12)	0.196 (3)	−0.0193 (12)	0.127 (2)	−0.0238 (14)
C1	0.0539 (10)	0.0420 (10)	0.0613 (11)	0.0052 (7)	0.0396 (9)	0.0001 (7)
C2	0.0467 (9)	0.0415 (9)	0.0463 (9)	0.0003 (7)	0.0310 (7)	0.0004 (6)
C3	0.0464 (12)	0.0355 (11)	0.0489 (12)	0.0000	0.0305 (11)	0.0000
C4	0.0617 (15)	0.0373 (13)	0.0668 (15)	0.0000	0.0422 (13)	0.0000
C5	0.0507 (10)	0.0452 (10)	0.0583 (10)	0.0013 (7)	0.0385 (9)	0.0012 (7)
C6	0.0697 (13)	0.0467 (11)	0.1048 (17)	−0.0001 (9)	0.0666 (13)	0.0035 (10)
C7	0.095 (2)	0.0386 (15)	0.121 (3)	0.0000	0.075 (2)	0.0000
C8	0.0581 (12)	0.0590 (12)	0.0988 (16)	0.0032 (9)	0.0531 (12)	0.0003 (11)
C9	0.0824 (16)	0.116 (2)	0.0638 (13)	−0.0166 (15)	0.0475 (13)	0.0137 (13)

Geometric parameters (Å, º) top

N10—C6	1.143 (3)	C7—H7B	0.9600
C1—C2	1.386 (2)	C7—H7C	0.9600
C1—C4	1.393 (3)	C7—H7Aⁱ	0.9600
C2—C3	1.396 (3)	C7—H7Bⁱ	0.9600
C2—C5	1.532 (3)	C7—H7Cⁱ	0.9600
C4—C7	1.516 (4)	C8—H8A	0.9600
C5—C6	1.467 (3)	C8—H8B	0.9600
C5—C8	1.537 (4)	C8—H8C	0.9600
C5—C9	1.537 (3)	C9—H9A	0.9600
C1—H1	0.9300	C9—H9B	0.9600
C3—H3	0.9300	C9—H9C	0.9600
C7—H7A	0.9600

C2—C1—C4	121.3 (2)	H7A—C7—H7C	109.00
C1—C2—C3	118.9 (2)	H7A—C7—H7Aⁱ	141.00
C1—C2—C5	119.87 (19)	H7A—C7—H7Bⁱ	56.00
C3—C2—C5	121.14 (16)	H7A—C7—H7Cⁱ	56.00
C2—C3—C2ⁱ	120.95 (19)	H7B—C7—H7C	109.00
C1—C4—C7	120.62 (12)	H7Aⁱ—C7—H7B	56.00
C1—C4—C1ⁱ	118.8 (2)	H7B—C7—H7Bⁱ	141.00
C1ⁱ—C4—C7	120.62 (12)	H7B—C7—H7Cⁱ	56.00
C2—C5—C6	110.37 (19)	H7Aⁱ—C7—H7C	56.00
C2—C5—C8	112.78 (16)	H7Bⁱ—C7—H7C	56.00
C2—C5—C9	109.05 (18)	H7C—C7—H7Cⁱ	141.00
C6—C5—C8	105.75 (19)	H7Aⁱ—C7—H7Bⁱ	109.00
C6—C5—C9	108.60 (17)	H7Aⁱ—C7—H7Cⁱ	109.00
C8—C5—C9	110.2 (2)	H7Bⁱ—C7—H7Cⁱ	109.00
N10—C6—C5	177.2 (4)	C5—C8—H8A	109.00
C2—C1—H1	119.00	C5—C8—H8B	109.00
C4—C1—H1	119.00	C5—C8—H8C	110.00
C2—C3—H3	120.00	H8A—C8—H8B	109.00
C2ⁱ—C3—H3	120.00	H8A—C8—H8C	109.00
C4—C7—H7A	109.00	H8B—C8—H8C	109.00
C4—C7—H7B	109.00	C5—C9—H9A	109.00
C4—C7—H7C	109.00	C5—C9—H9B	109.00
C4—C7—H7Aⁱ	109.00	C5—C9—H9C	109.00
C4—C7—H7Bⁱ	109.00	H9A—C9—H9B	109.00
C4—C7—H7Cⁱ	109.00	H9A—C9—H9C	109.00
H7A—C7—H7B	109.00	H9B—C9—H9C	109.00

C4—C1—C2—C3	0.0 (2)	C1—C2—C5—C6	−157.97 (17)
C4—C1—C2—C5	−175.93 (12)	C1—C2—C5—C8	−40.0 (2)
C2—C1—C4—C7	−180.00 (12)	C1—C2—C5—C9	82.8 (2)
C2—C1—C4—C1ⁱ	0.00 (17)	C3—C2—C5—C6	26.2 (2)
C1—C2—C3—C2ⁱ	0.02 (18)	C3—C2—C5—C8	144.25 (15)
C5—C2—C3—C2ⁱ	175.86 (12)	C3—C2—C5—C9	−92.99 (19)

Symmetry code: (i) −x, y, −z+3/2.

Acknowledgements

The authors thank Mr Sunil Kumar, Research Scholar, Department of Chemistry, Periyar Maniammai Institute of Science and Technology, for the gift of a sample.

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