Synthesis, Structural, and Docking Studies of O – Flurocyanoacetanilide. (2- Cyano -N-(Furan-2-Ylmethyl) Acetamide)

Synthesis, Structural, and Docking Studies of O – Flurocyanoacetanilide. (2- Cyano -N-(Furan-2-Ylmethyl) Acetamide)

Chandrashekara, S. Subhadramma b, B.P. Siddarajuc, Shivalingegowdad. and

J. Saravanane

aDepartment of Chemistry, PES College of Engineering, Mandya 571401, Karnataka. bDepartment of Physics, Vijaya College, Basavanagudi, Bangalore -560004.

cDepartment of Engg.Chemistry, Cauvery Institute of Technology, Sundhahalli, Mandya, Karnataka. 571401,

dDepartment of Physics, PES College of Engineering, Mandya 571401, Karnataka. eDept.of Pharmaceutical Chemistry, PES College of Pharmacy, Hanumanthnagar, Bangalore-560050.

Abstract The title compound have been prepared, characterized and crystallized to determine their crystal structures. The compounds crystallize in space groups, P21/c, monoclinic with unit cell parameters, a= 4.8093(4) Ã…, b= 14.9495(16) Ã…, c= 11.4969(11) Ã…, = 93.482(3)o, V = 825.06(14)Ã…3 containing four

asymmetric molecules. The molecules are packed in the crystal lattice with hydrogen bonding of the type C-H—O. Oxygen atom O1 is involved in the hydrogen bonding with bridge distances 3.3960(17) Ã… and 2.8483(16)Ã… respectively.

Index Terms Activity, Antibacterial, Characterization, Crystal, Acetone, Fluoro Aniline, Hydrogen bonding and Structure

1. INTRODUCTION

   Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen. The classes of compounds containing such rings are also referred to as furans. The five-member furan ring adopts an envelope-like conformation. All bond lengths [1] and angles are within normal ranges. Acylamide compounds have gained widely attention due to their important medical activity. Recently, the synthesis and medical activities of some heterocyclic derivatives containing the acylamide moiety have been reported [2] & [4]. In continuation of our work is on the synthesis of acetamide derivatives [3]. A number of furan and acylamide derivatives have been synthesized, characterized and reported to have significant and diverse biological activities such as antimicrobial [5], analgesic [6], anti-inflammatory [7], antioxidant [8], antitumor 9] and local anesthetic [10] activities.

2. PREPARATION AND CHARACTERIZATION OF COMPOUND

   2.1 Synthesis of O-flurocyanoacetanilide

   An equi-molar mixture of O-fluro aniline and ethyl cyano acetate were mixed in a conical flask and the mixture was heated under micro wave irradiation at 700w for 3 minutes with an interval of 20 second each time and mixture was poured to a beaker cooled and the solid obtained was size reduced washed with ethane and recrystallized from acetone: water mixture (70:30 ratio).

3. CRYSTAL STRUCTURE DETERMINATION OF COMPOUND

   Fig.1 An ORTEP diagram with 50% thermal ellipsoid probability for the compound

   Fig. 2 – Crystal packing diagram for the compound

   Fig. 3 Ligplot of the compound showing the molecular interactions

   Fig. 4 Compound showing the molecular interactions

   TABLE 1

   CRYSTAL DATA FOR COMPOUND

   Parameter	Compound
   Empirical formula	C8 H8 N2 O2
   Formula weight	164.16
   Temperature	293(2) K
   Wavelength	0.71073 Ã…
   Crystal system, space group	Monoclinic, P21/c
   Unit cell dimensions	a = 4.8093(4)Ã… alpha = 90o b = 14.9495(16)Ã… beta = 93.482(3)o c = 11.4969(11)Ã… gamma = 90o.
   Volume	825.06(14) Ã…3
   Z, Calculated density	4, 1.322 Mg/m3
   Absorption coefficient	0.098 mm-1
   F(000)	344
   Crystal size	0.30 x 0.20 x 0.20 mm
   Theta range for data collection	2.24 to 24.98o
   Limiting indices	-5<=h<=5, -17<=k<=17, -12<=l<=13
   Reflections collected / unique	7302 / 1455 [R(int) = 0.0265]
   Completeness to theta	24.98 99.90%
   Absorption correction	Semi-empirical from equivalents
   Max. and min. transmission	0.988 and 0.946
   Refinement method	Full-matrix least-squares on F2
   Data / restraints / parameters	1455 / 0 / 113
   Goodness-of-fit on F2	1.076
   Final R indices [I>2sigma(I)]	R1 = 0.0364, wR2 = 0.0950
   R indices (all data)	R1 = 0.0463, wR2 = 0.1029
   Largest diff. peak and hole	0.146 and -0.131 e. Ã…3

4. RESULTS AND DISCUSSION

   The final atomic fractional coordinate (x104 Ã…) and their equivalent isotropic displacement parameters (Ã…2×103) of the non hydrogen atoms are given in Table 2. The bond distances and bond angles are given in Table 3 for the molecule. It is seen from the table that the bond distances and angles in the compound within the normal range of e.s.ds. The molecules are packed in the unit cells nicely by inter and intra hydrogen bondings in Table 4. The oxygen O atom in compound is involved in hydrogen bonding of the type: C(2)H(2A)—

   O(1), 3.3960 (17) Ã… and N(23H(2)—-O(1) with hydrogen bond distance 2.843(16)Ã…. The compound, due to extensive hydrogen bonding network, the molecules are arranged in a spiral manner in the unit cell and packing of molecule parallel to the longest x-axis. The packing consideration of the molecule due to extensive hydrogen bonding leads to stability of the molecule in the unit cell. The antibacterial activity may be attributed to the inter and intra hydrogen bonding interactions and also the propensity of the molecules to pack together as dimmers involving N-H—O and C-HO bonding interactions lead to the possible variation in the nature of packing motifs (fig. 4). These kind of interactions involving N-H—O and C-HO interactions may be responsible for the biological activity of the molecule which is responsible for molecular basis for drug design as observed in the case of crystal structure of atovaquone [11].

   TABLE 2

   ATOMIC COORDINATES (X104) AND EQUIVALENT ISOTROPIC DISPLACEMENT PARAMETERS (A2 X 103)

   Atoms	X	y	Z	U(eq)
   C(1)	3983(4)	685(1)	12780(2)	59(1)
   C(2)	2629(3)	418(1)	11671(1)	51(1)
   C(3)	3693(3)	992(1)	10705(1)	44(1)
   C(4)	2437(3)	2039(1)	9129(1)	57(1)
   C(5)	1117(3)	1802(1)	7978(1)	48(1)
   C(6)	-1009(4)	2132(1)	7321(2)	70(1)
   C(7)	-1248(4)	1599(2)	6295(2)	81(1)
   C(8)	729(5)	993(2)	6400(2)	78(1)
   N(1)	5079(5)	909(1)	13628(2)	94(1)
   N(2)	1785(3)	1413(1)	10046(1)	47(1)
   O(1)	6196(2)	1036(1)	10576(1)	71(1)
   O(2)	2222(2)	1091(1)	7430(1)	65(1)

   TABLE 3

   D H A	d(D H)	d(H A)	d(D A)	<(DHA)
   C(2)- H(2A)…O(1)#1	0.97	2.56	3.3960(17 )	145
   N(2)-H(2)…O(1)#1	0.801(18 )	2.054(18 )	2.8483(16 )	171.3(17 )

   BOND LENGTHS [A] AND ANGLES [DEG]

   Atoms	Length
   C(1)-N(1)	1.131(2)
   C(1)-C(2)	1.453(2)
   C(2)-C(3)	1.516(2)
   C(3)-O(1)	1.2234(16)
   C(3)-N(2)	1.3153(19)
   C(4)-N(2)	1.4578(19)
   C(4)-C(5)	1.476(2)
   C(5)-C(6)	1.328(2)
   C(5)-O(2)	1.3601(18)
   C(6)-C(7)	1.422(3)
   C(7)-C(8)	1.314(3)
   C(8)-O(2)	1.355(2)
   N(1)-C(1)-C(2)	178.0(2)
   C(1)-C(2)-C(3)	109.58(13)
   O(1)-C(3)-N(2)	124.18(14)
   O(1)-C(3)-C(2)	119.85(13)
   N(2)-C(3)-C(2)	115.97(12)
   N(2)-C(4)-C(5)	113.25(13)
   C(6)-C(5)-O(2)	109.61(15)
   C(6)-C(5)-C(4)	134.05(17)
   O(2)-C(5)-C(4)	116.34(13)
   C(5)-C(6)-C(7)	106.53(17)
   C(8)-C(7)-C(6)	106.79(17)
   C(7)-C(8)-O(2)	110.30(18)
   C(3)-N(2)-C(4)	123.42(13)
   C(8)-O(2)-C(5)	106.76(14)

   TABLE 4

   HYDROGEN BONDS [A AND DEG] o

5. CONCLUSION

   Substituted acylamide with electron withdrawing and methoxy groups play a vital role in their biological activity as antibacterial. The results of the present research indicate that the molecule is nicely packed in the unit cell with extensive hydrogen bonding network. They exhibit a greater antibacterial activity. It may be interesting to see that more different substituted groups on the acylamide molecule could be a future investigation followed by their three-dimensional structure determination.

6. ACKNOWLEDGMENT

   The authors thank Dr. Babu Varghese for his help in determining the structures of the molecules and also to utilize the facilities available at Sophisticated Analytical Instrument Facility (SAIF) Center of IIT Madras. The authors also thank Mr. Vamsy for his help in preparing this manuscript.

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