This document describes the crystal structure of the compound terbinafine, which was analyzed using X-ray single crystal diffraction. Key findings include: - Terbinafine crystallizes in the monoclinic space group P21/n with unit cell parameters a=5.9181(3)Å, b=29.4239(14)Å, c=11.429 β=97.92 ̊, V=1971.24(16) Å3, Z=4. - Two water molecules were present in the crystal structure unit cell and engaged in hydrogen bonding, providing stability to the structure. - The two benzene rings in the structure are essentially planar, while the side

1. ISSN (Print): 2328-3777, ISSN (Online): 2328-3785, ISSN (CD-ROM): 2328-3793
American International Journal of
Research in Formal, Applied
& Natural Sciences
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AIJRFANS is a refereed, indexed, peer-reviewed, multidisciplinary and open access journal published by
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Crystal structure of [(2E)-6,6-dimethylhept-2-en-4-yn-1-
yl](methyl)(naphtha-1-ylmethyl)amine( Terbinafine)
Tiwari R.K., MishraBharti
Department of Physics, Jiwaji University-474011, Gwalior (M.P.), India
I. Introduction
Title compound (Terbinafine) C21H25N became available first time in 1991 in Europe and in 1996 in USA. It is a
synthetic allylamine antifungle compound. It is recently introduced, orally active, antifungal belonging to the
allylamines class1
of synthetic antifungal agents. The structurally related topical antifungal naftifine 2
was the
prototype of these compounds from which it was developed during a programme of chemical synthesis3
. The
biological and clinical properties of the allylamines have recently been reviewed4
. Title compound in common
with naftifine and related allylamines, acts by blocking fungal ergosterol biosynthesis5-7
. Terbinafine is highly
lipophilic in nature and tends to accumulate in skin, nails and fatty tissues. It prevents conversion of squalene to
lanosterol. The present paper is related with its three- dimensional structure.
II. Experimental Details
Nice beautiful colorless crystals of title compound were grown by the slow evaporation from its
solution in Acetone at room temperature. The density of the crystals was measured by floatation method in a
mixture of Benzene and Carbon tetra chloride. The measured density was 1.054 mg/m3
whereas calculated
density is 1.0966 mg/m3
. The molecular weight of the sample is 291.43 g/mol. and melting point is 193˚C. The
IUPAC name of Terbinafine is [(2E)-6, 6-dimethylhept-2-en-4-yn-1-yl] (methyl) (naphtha-1-ylmethyl) amine.
The unit cell parameters were determined by a computerized automatic Bruker axs Kappa apex 2 CCD
diffractometer at Sardar Patel University, Vallabh Vidyanagar, Gujurat e ell pa amete s a e a 91 1 3
9 39 1 11 93 and β 97 9 ˚ 0 us t e spa e g oup was dete mined to e P 1/n with
monoclinic crystal system and Z=4. The preliminary crystal data is given in Table 1.
III. Data collection and structure solution
The complete three dimensional intensity data collection was done at Sardar Patel University, Vallabh
Vidyanagar, Gujarat on a computerized automatic Bruker axs Kappa apex 2 CCD diffractometer. The
temperature of crystal during data collection was 293K. The X- ay adiation used was Mokα (0.7107 Å). All the
data were corrected for Lorentz and polarization effects but no absorption correction was done because of very
small absorption coefficient. The data collection was done y a θ ange of 1 to 7 ˚ e enti e data we e
collected where h varies from -6 to 7, k from -38 to 38 and l from -14 to 7. In all 17396 reflection were
measured out of which 4512 were unique reflections. Each intensity measurement involved in a scan over the
reflection peak height. The structure was solved by direct method using SHELXS-978
.
IV. Refinement
The positional parameters which were obtained from SHELXS-97 and their isotropic temperature
factors were subjected to refinement by SHELXL-979
refinement program. After 4 cycles of refinement the R
factor dropped to 0.1154. Further refinement of the structure was carried out with individual anisotropic
temperature factors of the form:
Exp.[(U11h2
+U22k2
+U33l2
+2U12hk+2U23kl+2U13hl)]
reduced R-factor to 0.1007. At this stage the hydrogen atoms were fixed by geometrical considerations and
refined subsequently with isotropic temperature factors which were taken from the corresponding non- hydrogen
atoms.
Abstract: The title molecule [(2E)-6,6-dimethylhept-2-en-4-yn-1-yl ](methyl)(naphtha-1-ylmethyl)amine,
C21H25N (Terbinafine) is characterized by X-ray single crystal diffraction analysis. The compound
crystallizes in the monoclinic space group P21/n with a=5.9181(3)Å, b=29.4239(14)Å, c=11.429
β=97.92˚(0), Volume 1971.24(16) Å3
and Z=4. The two Benzene rings in the structure are essential planer,
but the side chain is inclined with a gle of 7.21˚. There is i teresti g observ tio i this structure.
During crystallization, two water molecules have shown their presence in the unit cell. These water
molecules are engaged in hydrogen bonding and thus providing the stability to the structure.
Keywords: Single crystal diffraction, Hydrogen bond, Crystallization etc.

2. R.K Tiwari et al., American International Journal of Research in Formal, Applied & Natural Sciences, 6(2), March-May 2014, pp. 114-118
AIJRFANS 14-259; © 2014, AIJRFANS All Rights Reserved Page 115
Refinement of the structure was terminated after three more cycles of refinement when all the
s ifts in t e pa amete s e ame mu small t an t e o esponding e s d’s e final R-value was 0.0951 for all
the 17396 observed unique reflections. The final positional and thermal parameters of non-hydrogen atoms are
listed in Table 2.
V. Results and discussion
The ORTEP10
view of the molecule with numbering scheme is shown in Fig 2. The bond lengths and
angles involving non-hydrogen atoms are listed in Table 3. The two Benzene rings in the structure are essential
plane ut t e side ain is in lined wit an angle of 37 1˚ The bond lengths and angles in the Benzene ring
have usual variations, but the C(1)-C(11) bond in unusually long of 1.499(4) Å. This elongation may be due to
extension of Benzene ring electrons delocalization along this bond. Similarly the chain from C(11)-C(23) is a
stretched one having normal bond distances. There is also nothing unusual about the tetrahedral geometry
around C(23). All the bond lengths and angles are normal. The relevant torsional angles are shown in Table 4.
There is an interesting observation in this structure. During crystallization, two water molecules have
shown their presence in the unit cell. These water molecules are engaged in hydrogen bonding and thus
providing the stability to the structure. The possible hydrogen bonds are listed in Table 5. The packing of the
molecules viewed along a, b and c axes are shown in Figs 3, 4, 5 and 6 respectively.
References
[1] G.Petranyi, N.S.Ryder, A.Stutz, Allylamine derivatives new class of synthetic antifungal agents
inhibiting fungal squalene epoxidase Science, 1984, 224, 1239-41
[2] A.Georgopoulos, G.Petranyi, H.Mieth, J.Drews, in vitro activity of naftiline, a new antifungal agent,
Antimicrob agents chemother, 1981, 19, 386-9
[3] A.Stutz, Synthesis and structure- activity correlations within allylamine antimycotics, Ann N Y Acad
Sci, 1988, 544, 46-62
[4] N.S.Ryder, H.Mieth, Allylamine antifungal drugs Curr Top Med Mycol, 1991, 4, 158-88
[5] N.S.Ryder, G.Seidl, P.F.Troke, Effect of the antimycotic drug naftifine on growth of and sterol
biosynthesis in candida albicans, Antimicrob Agents Chemother, 1984, 25, 483-7
[6] N.S.Ryder, Specific inhibition of fungal biosynthesis by SF 86-327,a new allylamine antimycotic agent,
Antimicrob Agents Chemother, 1985, 27, 252-6
[7] N.S.Ryder, M-C Dupont, Inhibition of squalene epoxidase by allylamine antimycotic compounds, a comparative study of the
fungal andmammalian enzymes Biochem J, 1985, 230, 765-70
[8] G M S eld i “ SHELXS-97 P og am fo t e solution of ystal st u tu e” 1997
[9] G M S eld i “SHELXL-97 P og am fo ystal st u tu e dete mination” 1997
[10] C K Jo nson “OR EP Repo t ORNL-3794 Ook Ridge National La o ato y ennessee U S A” 19
Fig.1 Molecular structure of compound
Table 1: Crystallographic data for title compound
Empirical formula C21 H25N
Formula weight 325.45
Temperature 293(2) K
Wavelength 0.71073 Å (Mokα
Crystal system, space group monoclinic, P21/n
Unit cell dimensions a=8.89 aa a=5.9181(3) Å, b=29.4239(14)Å
11 93 β 97 9 0 ˚
Volume 1971.24(16) Å3
Z, Calculated density 4, 1.0966 Mg/m3
Absorption coefficient 0.070 mm-1
F(000) 704
Theta range for data collection 1.4 to 27.5 deg
Limiting indices -6<=h<=7, -38<=k<=38, -14<=l<=7
Reflections collected / unique 17396 / 4512 [R(int) = 0.027]
Completeness to theta 27.5 99.0 %
Refinement method Full-matrix least-squares on F2

3. R.K Tiwari et al., American International Journal of Research in Formal, Applied & Natural Sciences, 6(2), March-May 2014, pp. 114-118
AIJRFANS 14-259; © 2014, AIJRFANS All Rights Reserved Page 116
Data / restraints / parameters 4512 / 0 / 233
Goodness-of-fit on F2
1.065
Final R indices [I>2sigma (I)] R1 = 0.0683, wR2 = 0.1939
R indices (all data) R1 = 0.0951, wR2 = 0.2146
Largest diff. peak and ho 0.53 and -0.32 e.Å
Fig. 2 ORTEP view of molecule
Fig. 3 Packing seen down a-axis Fig. 4 Packing seen down b-axis
Fig. 5 Packing seen down c-axis Fig. 6 Packing of the unitcell
Table 2: Atomic coordinates (x 104 2
x103
) for
non-hydrogen. U (eq) is defined as one third of the trace of the orthogonalized Uij tensor.
X Y Z Ueq
OW(2) 0.740 (2) 0.2441 (5) 0.139 (2) 0.050 (3)
OW(1) 0.743 (2) 0.2414 (5) 0.147 (2) 0.0426 (17)
C(12) 1.1656 (5) 0.23898 (10) −0 0 61 3 0.0595 (7)
N(1) 0.9532 (3) 0.26658 (6) −0 071 17 0.0447 (5)
C(13) 0.8008 (4) 0.24985 (7) −0 17 3 0.0462 (5)
C(6) 0.7372 (4) 0.36422 (7) −0 1 0.0523 (6)
C(1) 0.8127 (5) 0.34646 (8) −0 1060 0.0522 (6)
C(16) 0.7217 (5) 0.12353 (9) −0 1 0.0613 (7)
C(15) 0.7940 (5) 0.16986 (9) −0 1 0.0573 (7)
C(11) 1.0157 (4) 0.31568 (8) −0 0 0.0541 (6)
C(14) 0.7379 (5) 0.20124 (9) −0 1690 3 0.0534 (6)
C(17) 0.6573 (5) 0.08516 (9) −0 1 3 0.0645 (7)
C(7) 0.8548 (5) 0.35660 (9) −0 319 0.0608 (7)
C(8) 0.7725 (7) 0.37409 (11) −0 3 0.0808 (10)
C(3) 0.5005 (7) 0.38507 (11) −0 0316 0.0849 (11)

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C(5) 0.5344 (5) 0.39082 (8) −0 391 3 0.0665 (8)
C(18) 0.5693 (6) 0.03833 (9) −0 99 3 0.0725 (9)
C(10) 0.4556 (7) 0.40692 (11) −0 3 30 0.0894 (12)
C(2) 0.6968 (6) 0.35758 (9) −0 01 1 3 0.0687 (8)
C(9) 0.5696 (8) 0.39871 (12) −0 0.0960 (13)
C(4) 0.4209 (6) 0.40035 (10) −0 1 07 0.0820 (10)
C(21) 0.6751 (15) 0.0120 (2) −0 3 13 7 0.198 (4)
C(19) 0.6519 (17) 0.01448 (19) −0 13 9 6 0.217 (5)
C(20) 0.3262 (9) 0.03818 (18) −0 7 1 0.311 (8)
Table 3: ] b ˚] f - hydrogen atoms
C(12)—N(1) 1.491 (3)
N(1)—C(13) 1.497 (3)
N(1)—C(11) 1.501 (3)
C(13)—C(14) 1.485 (3)
C(6)—C(7) 1.415 (4)
C(6)—C(5) 1.424 (4)
C(6)—C(1) 1.432 (4)
C(1)—C(2) 1.371 (4)
C(1)—C(11) 1.499 (4)
C(16)—C(17) 1.190 (4)
C(16)—C(15) 1.429 (4)
C(15)—C(14) 1.311 (4)
C(17)—C(18) 1.471 (4)
C(7)—C(8) 1.371 (4)
C(8)—C(9) 1.393 (6)
C(3)—C(4) 1.349 (6)
C(3)—C(2) 1.407 (5)
C(5)—C(10) 1.404 (5)
C(5)—C(4) 1.414 (5)
C(18)—C(20) 1.427 (6)
C(18)—C(19) 1.473 (6)
C(18)—C(21) 1.505 (7)
C(10)—C(9) 1.345 (6)
C(7)—C(6)—C(5) 118.2 (3)
C(7)—C(6)—C(1) 123.1 (2)
C(5)—C(6)—C(1) 118.7 (3)
C(2)—C(1)—C(6) 119.6 (3)
C(2)—C(1)—C(11) 118.8 (3)
C(12)—N(1)—C(13) 112.14 (19)
C(12)—N(1)—C(11) 109.24 (19)
C(13)—N(1)—C(11) 112.00 (18)
C(14)—C(13)—N(1) 112.8 (2)
Table 4: Torsion angles [deg]
C(12)—N(1)—C(13)—C(14) 56.5 (3)
C(11)—N(1)—C(13)—C(14) 179.7 (2)
C(7)—C(6)—C(1)—C(2) 176.2 (2)
C(5)—C(6)—C(1)—C(2) −3 3
C(7)—C(6)—C(1)—C(11) − 1 3
C(5)—C(6)—C(1)—C(11) 175.9 (2)
C(17)—C(16)—C(15)—C(14) 110 (10)
C(2)—C(1)—C(11)—N(1) 76.9 (3)
C(6)—C(1)—C(11)—N(1) −10 3
C(12)—N(1)—C(11)—C(1) −17
C(13)—N(1)—C(11)—C(1) 56.3 (3)
C(16)—C(15)—C(14)—C(13) −17 7 3
N(1)—C(13)—C(14)—C(15) −117 3
C(15)—C(16)—C(17)—C(18) − 16
C(5)—C(6)—C(7)—C(8) −0 7
C(1)—C(6)—C(7)—C(8) 179.2 (2)
C(6)—C(7)—C(8)—C(9) −1
C(7)—C(6)—C(5)—C(10) 2.2 (4)
C(1)—C(6)—C(5)—C(10) −177 7 (2)
C(7)—C(6)—C(5)—C(4) −177 3
C(1)—C(6)—C(5)—C(4) 2.8 (4)
C(16)—C(17)—C(18)—C(20) 6 (9)
C(16)—C(17)—C(18)—C(19) −11 9
C(16)—C(17)—C(18)—C(21) 129 (9)
C(4)—C(5)—C(10)—C(9) 177.9 (3)
C(6)—C(5)—C(10)—C(9) −1 6
C(6)—C(1)—C(11) 121.6 (2)
C(17)—C(16)—C(15) 178.0 (3)
C(14)—C(15)—C(16) 124.9 (3)
C(1)—C(11)—N(1) 113.30 (19)
C(15)—C(14)—C(13) 123.1 (3)
C(16)—C(17)—C(18) 178.0 (3)
C(8)—C(7)—C(6) 120.4 (3)
C(7)—C(8)—C(9) 120.7 (4)
C(4)—C(3)—C(2) 120.0 (3)
C(10)—C(5)—C(4) 122.5 (3)
C(10)—C(5)—C(6) 118.8 (3)
C(4)—C(5)—C(6) 118.7 (3)
C(20)—C(18)—C(17) 110.6 (3)
C(20)—C(18)—C(19) 111.9 (6)
C(17)—C(18)—C(19) 109.9 (3)
C(20)—C(18)—C(21) 111.5 (6)
C(17)—C(18)—C(21) 109.2 (3)
C(19)—C(18)—C(21) 103.4 (6)
C(9)—C(10)—C(5) 121.7 (4)
C(1)—C(2)—C(3) 121.2 (3)
C(10)—C(9)—C(8) 120.2 (3)
C(3)—C(4)—C(5) 121.7 (3)

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C(6)—C(1)—C(2)—C(3) 1.9 (4)
C(11)—C(1)—C(2)—C(3) −177
C(4)—C(3)—C(2)—C(1) 1.1 (5)
C(5)—C(10)—C(9)—C(8) −0 6 6
C(7)—C(8)—C(9)—C(10) 2.2 (5)
C(2)—C(3)—C(4)—C(5) −
C(10)—C(5)—C(4)—C(3) −179 3
C(6)—C(5)—C(4)—C(3) 0.3 (4)
Table 5: Possible Hydrogen Bonds (Å)
D-H D….A H...A ∟D-H......A
C(12)-H(12A) C(12 )...OW(2) (1) H(12A)...OW(2) (1) C(12)-H(12A) ...OW(2) (1)
0.960(.003) 3.734(.013) 2.968(.012) 137.65( 0.33)
C(12)–H(12B) C(12)...OW(2) (2) H(12B)...OW(2) (2) C(12)-H(12B)...OW(2) (2)
0.960(.003) 3.736(.018) 2.891(.017) 147.41( 0.37)
C(12)-H(12B) C(12)...OW(1) (2) H(12B)...OW(1) (2) C(12) -H(12B)...OW(1) (2)
0.960(.003) 3.628(.018) 2.779(.017) 147.76( 0.38)
C(13)-H(13B) C(13)...OW(2) (2) H(13B)...OW(2) (2) C(13) –H(13B)...OW(2) (2)
0.970(.003) 3.561(.016) 2.661(.015) 154.50( 0.35)
C(13)-H(13B) C(13)...OW(1) (2) H(13B)...OW(1) (2) C(13)-H(13B)...OW(1) (2)
0.970(.003) 3.509(.016) 2.622(.015) 152.17( 0.35)
C(7)-H(7) C(7)...OW(2) (2) H(7)...OW(2) (2) C(7)-H(7)...OW(2) (2)
0.930(.003) 3.805(.014) 2.975(.014) 149.33( 0.32)
C(7)-H(7) C(7)...OW(1) (2) H(7)...OW(1) (2) C(7)-H(7)...OW(1) (2)
0.930(.003) 3.738(.014) 2.893(.013) 151.68( 0.32)
C(13) -H(13A) C(13)...OW(2) (3) H(13A)...OW(2) (3) C(13)-H(13A)...OW(2) (3)
0.970(.003) 3.691(.013) 3.000(.013) 129.29( 0.30)
C(13)-H(13A) C(13)...OW(1) (3) H(13A)...OW(1) (3) C(13)-H(13A)...OW(1) (3)
0.970(.003) 3.605(.013) 2.889(.013) 131.42( 0.30)
Equivalent positions:
( 1) x+1,+y,+z
( 2) x+1/2,-y+1/2,+z-1/2
( 3) x-1/2,-y+1/2,+z-1/2