1-s2.0-S0022286004001723-main

Analysis of intermolecular interactions involving

halogens in substituted benzanilides

D. Chopra, T.N. Guru Row*

Solid State and Structural Chemistry Unit, Indian Institute of Science, C.V. Raman Avenue, Bangalore 560012, India

Received 22 December 2003; revised 9 March 2004; accepted 10 March 2004

Available online 12 October 2004

Abstract

Crystal structures of halogen-substituted benzanilides have been analyzed in terms of weak interactions involving halogens. The four

compounds namely 3-fluoro-N-(3-hydroxyphenyl)benzamide, 3-chloro-N-(3-hydroxyphenyl)benzamide, 3-fluoro-N-(4-methylphenyl)ben-

zamide and 3-chloro-N-(4-methylphenyl)benzamide crystallize in monoclinic symmetry. The packing modes in the crystalline lattice

generate motifs via NH O and OH O hydrogen bonds in structures 1 and 2 and via NH O hydrogen bond, weak CH F and

Cl Cl interactions in structures 3 and 4. These structures when compared with the polymorphs of benzanilide show no orientational disorder

and depict subtle conformational changes, which are directed by both strong hydrogen bonds and weak interactions involving halogens.

q 2004 Elsevier B.V. All rights reserved.

Keywords: Weak interactions; Hydrogen bonds; Polymorphism; Molecular conformation

1. Introduction

Design and synthesis of new materials with desired

physical and chemical properties involve the generation and

study of structural motifs in crystals which is essentially

guided by precise topological control through the manipu-

lation of intermolecular interactions [1]. This necessitates

the understanding of the nature of weak non-covalent

interactions, which dictate conformational and packing

features in crystalline solids. There are a rich variety of such

intermolecular interactions, which serve as tools in

engineering such molecular assemblies [2].

Hydrogen bonds are amongst the most studied of such

intermolecular interactions [36]. In recent years molecular

assemblies have been identified involving much weaker

non-covalent interactions to serve as tools in crystal

engineering. Some of these are the halogenhalogen

interactions [7,8], charge transfer [9], electrostatic forces

[1012], and pp stacks [13,14]. Hydrogen bonds [1519]are the most important and decisive element in crystal

engineering. The interactions involving hydrogen bond are

of a highly directional nature and the strength depends on

the electronegativity of the element, which accepts the

hydrogen atom. Some of the well-known interactions

involving hydrogen bond are O H N, N H O,

CH O, CH N, CH p and CH X [2023]and these provide well-defined molecular frameworks in

crystalline lattices. Interactions involving halogens,

especially, Cl and Br, have been analyzed both in terms of

their directional preferences and in terms of the strength of

their interaction [24,25]. In recent literature, the importance

of interactions involving fluorine as possible tools in crystal

engineering has been explored in greater detail [2629].

As a part of extending our work in evaluating weak

intermolecular interactions we report the crystal and

molecular structures of four differently substituted benza-

nilides (Fig. 1). Two of these contain a halogen atom

(X F, Cl; Compounds 1,2: Fig. 1) in the meta-position ofone of the two-phenyl rings with hydroxyl in the meta-

position of the other. The other two compounds have a

methyl group in the para-position of one of the phenyl rings

and a halogen atom (X F, Cl; Compounds 3,4: Fig. 1) inthe meta-position of the other. These compounds are

compared with the polymorphs of the parent benzanilide

[30,31] in an effort to gain insights into the possible

occurrence of polymorphs and the presence of orientational

disorder.

0022-2860/$ - see front matter q 2004 Elsevier B.V. All rights reserved.

doi:10.1016/j.molstruc.2004.03.011

Journal of Molecular Structure 733 (2005) 133141

www.elsevier.com/locate/molstruc

* Corresponding author. Tel.: 91-80-3942796; fax: 91-80-3601310.E-mail address: [email protected] (T.N.G. Row).

http://www.elsevier.com/locate/molstruc

2. Experimental

2.1. Synthesis

2.1.1. Compound 1 (3-fluoro-N-(3-hydroxyphenyl)

benzamide)

m-Fluorobenzoyl chloride (0.137 g,0.86 mmol) and

m-amino phenol(0.094 g,0.87 mmol) were taken along

with 10.0 ml of dry dichloromethane and the resulting

mixture stirred for 2 h under ice cold conditions. Compound

1 was isolated by solvent extraction with dichloromethane

and finally subjected to column chromatography packed

with silica and ethyl acetate/hexane was used as the eluant.

Routine M.P, IR, UVVIS and NMR analysis confirmed the

formation of compound 1. Crystals of suitable quality were

grown by solvent evaporation from a solution of the

compound in ethyl acetate/hexane mixture.

2.1.2. Compound 2 (3-chloro-N-(3-hydroxyphenyl)

benzamide)

m-Chloro benzoic acid (0.600 g,3.8 mmol) was taken

along with 10.0 ml of dry dichloromethane. Thionyl

Chloride (5.0 ml) was added and the mixture

was refluxed for 2 h. The product, m-chloro benzoyl

chloride, was distilled under vacuum. 3-Amino Phenol

(0.323 g, 2.9 mmol) was added under ice-cold conditions to

0.5 ml of the above product and the resulting mixture was

stirred for 3 h. Compound 2 was separated by solvent

extraction using dichloromethane and the organic layer

dried using sodium sulfate. The resultant was subjected to

column chromatography packed with silica and ethyl

acetate/hexane was used as the eluant. Routine M.P, IR,

UVVIS and NMR analysis confirmed the formation of

compound 2. Crystals of suitable quality were grown by

solvent evaporation from a solution of the compound in

ethyl acetate/hexane mixture.

2.1.3. Compound 3 (3-fluoro-N-(4-methylphenyl)

benzamide)

m-Fluorobenzoyl chloride (0.138 g,0.87 mmol) and

p-toluidine(0.093 g, 0.87 mmol) was taken along with

10.0 ml of dry dichloromethane and the resulting mixture

stirred for 2 h under ice cold conditions. Compound 3 was

isolated by solvent extraction with dichloromethane, the

organic layer dried using sodium sulfate and finally

subjected to column chromatography packed with silica

and ethyl acetate/hexane was used as the eluant. Routine

M.P, IR, UVVIS and NMR analysis confirmed the

formation of compound 3. Crystals of suitable quality

were grown by solvent evaporation from a solution of the

compound in ethyl acetate/hexane mixture.

2.1.4. Compound 4 (3-chloro-N-(4-methylphenyl)

benzamide)

m-Chloro benzoic acid(0.600 g,3.8 mmol)was taken

along with 10.0 ml of dry dichloromethane. Thionyl

chloride (5.0 ml) was added and the mixture was refluxed

for 2 h. The product m-benzoyl chloride was distilled

under vacuum. p-toluidine (0.300 g, 2.8 mmol) was added

under ice cold conditions to 0.5 ml of the above product

and the resulting mixture stirred for 3 h. Compound 4 was

separated by solvent extraction using dichloromethane and

the organic layer dried over sodium sulfate and finally

subjected to column chromatography which was packed

with silica and ethyl acetate/hexane was used as

the eluant. Routine M.P, IR, UVVIS and NMR analysis

confirmed the formation of compound 4. Crystals

of suitable quality were grown by solvent evaporation

from a solution of the compound in ethyl acetate/hexane

mixture.

2.2. X-ray diffraction

The single crystal data were collected at room

temperature on a Bruker AXS SMART APEX CCD

diffractometer. The X-ray generator was operated at 50 kV

and 35 mA using Mo Ka radiation. Data was collected

with v scan width of 0.38. A total of 606 frames werecollected in three different settings of f (08,908,1808)keeping the sample to detector distance fixed at 6.03 cm

and the 2u value fixed at 2258. The data was reducedusing SAINTPLUS [32] and an empirical absorption

Fig. 1. Structural diagram of the compounds.

D. Chopra, T.N.G. Row / Journal of Molecular Structure 733 (2005) 133141134

Fig. 2. (a) ORTEP diagram of 3-fluoro-N-(3-hydroxyphenyl)benzamide. (b) ORTEP diagram of 3-chloro-N-(3-hydroxyphenyl)benzamide. (c) ORTEP

diagram of 3-fluoro-N-(4-methylphenyl)benzamide. (d) ORTEP diagram of 3-chloro-N-(4-methylphenyl)benzamide.

D. Chopra, T.N.G. Row / Journal of Molecular Structure 733 (2005) 133141 135

Fig. 3. (a) Region of strong NH O, OH O, CH O interactions in Compound 1. (b) Region of strong NH O, OH O, CH O interactions in

Compound 2. (c) Regions of strong NH O hydrogen bonds and weak CH F interactions in Compound 3. (d) Regions of strong NH O hydrogen

bonds and weak Cl Cl interactions in Compound 4.


correction was applied using the package SADABS [32].

The crystal structures (14) were solved by direct

methods using SIR92 [33] and refined by full matrix

least squares method using SHELXL97 [34] present in the

program suite WINGX (Version 1.63.04a) [35]. All the

hydrogen atoms were located and refined isotropically.

Molecular diagrams (Fig. 2) were generated using ORTEP-

32 [36] and the packing diagrams (Fig. 3) were generated

using CAMERON [37]. Geometrical calculations were

done using PARST95 [38]. The details of the data

collection and refinement are given in Table 1, selected

dihedral angles are given in Table 2 and intermolecular

interactions are listed in Table 3.

3. Results

3.1. Structure of (3-fluoro-N-(3-hydroxyphenyl)benzamide)

Compound 1 crystallizes in the space group P21=n with

Z 4. The crystals are plate-like and show no evidencefor concomitant polymorphism or orientational disorder in

the crystal packing as was found in the parent compound

[30,31]. The dihedral angle between the least squares plane

through the two-phenyl rings and the dihedral angle

between the planes passing through the amido group and

each of the phenyl rings are listed in Table 2. Two strong

and well defined hydrogen bonds hold the molecules

Table 1

Crystal data

Data Compound 1 Compound 2 Compound 3 Compound 4

CCDC number 211783 211780 211782 211781

Formula C13H10N1O2 F1 C13H10Cl1N1O2 C14H12N1O1F1 C14H12Cl1N1O1

Formula weight 231.2 247.67 229.3 245.71

Temperature (K) 293(2) 293(2) 293(2) 293(2)

Radiation Mo Ka Mo Ka Mo Ka Mo KaWavelength (A) 0.71073 0.71073 0.71073 0.71073

Crystal system Monoclinic Monoclinic Monoclinic Monoclinic

Space group P21=n P21=n P21=c C2=c

a (A) 11.491(3) 12.069(3) 27.388(4) 28.578(1)

b (A) 5.061(1) 4.969(1) 5.337(7) 5.518(2)

c (A) 18.633(4) 18.831(4) 7.976(1) 15.437(6)

a (8) 90.00 90.00 90.00 90.00

b (8) 106.514(4) 102.295(4) 96.231(2) 102.830(6)

g (8) 90.00 90.00 90.00 90.00Volume (A3) 1038.90(13) 1103.5(4) 1158.91(4) 2373.37(37)

Z 4 4 4 8

Density (g/ml) 1.48 1.491 1.31 1.38

m (1/mm) 0.112 0.333 0.094 0.303F (000) 479.9 512 479.9 1024

u (min, max) (1.9, 27.5) (1.8, 26.4) (1.5, 26.4) (1.5, 26.4)

h; k; l (min, max) (214,14) (26,6)(223,24) (215,15) (26,6)(222,23) (234,31) (26,6) (29,9) (235,32) (26,6) (219,19)

No. refln. measured 7947 8329 8400 8973

No. unique refln 2271 2246 2313 2414

No of parameters 194 194 202 202

Refinement method Full matrix least Squares on F2 Full matrix least squares on F2 Full matrix least squares on F2 Full matrix least squares on F2

R_all 0.049 0.047 0.083 0.077

R_obs 0.043 0.036 0.065 0.063

wR2_all 0.117 0.103 0.152 0.141

wR2_obs 0.111 0.094 0.143 0.137

Drmax (eA23) 0.17 0.23 0.29 0.41

Drmin (eA23) 20.22 20.20 20.14 20.16

GooF 1.057 1.025 1.188 1.180

Table 2

Selected dihedral angles between least squares planes

Compound 1 (8) Compound 2 (8) Compound 3 (8) Compound 4 (8) Polymorph 1 [30]

Plane 1 and 3 2.78(4) 3.76(5) 62.43(7) 56.01(8) 62.6*

Plane 2 and 3 22.02(6) 27.67(8) 32.40(11) 29.97(12) 31.3*

Plane 1 and 2 23.45(6) 29.40(8) 28.37(12) 27.91(12) 31.6*

Plane 1, the phenyl ring C2/C7, Plane 2, the amido group N1C1O2, Plane 3, the phenyl ring C8/C13.


together in the crystal lattice, OH O resulting in a dimer

across the center of symmetry and NH O forming a

chain along [010] (Table 3, Fig. 4a). In addition a CH O

interaction, provides further stabilization to the formation of

the dimer in the crystal lattice (Table 3, Fig. 4a).

3.2. Structure of (3-chloro-N-(3-hydroxyphenyl)benzamide)

Compound 2 is isomorphous to compound 1 crystallizing

in P21=n with Z 4: Here again there is neither concomitantpolymorphism nor orientational disorder as found in the

parent compound. [30,31]. Table 2 lists the angle between

the least squares planes between the phenyl rings and the

dihedral angles subtended by the amido group with each

phenyl ring. The packing characteristics are similar to the

fluoro analogue with two significant intermolecular inter-

actions, OH O generating dimers in the ac plane,

NH O forming chains along [010] (Table 3, Fig. 4b)

along with a CH O interaction stabilizing the dimer.

3.3. Structure of (3-fluoro-N-(4-methylphenyl)benzamide)

Compound 3 does not display any concomitance and has

no orientational disorder while crystallizing in the space

group P21=c with Z 4: The conformation defers signifi-cantly from those found in compound 1 and 2 with the

dihedral angle between the planes of the two phenyl rings

being 62.43(7)8 while the dihedral angles between the least

squares plane through the amido group and each of the

phenyl rings being similar to those of the parent compound

(Table 2). The most significant intermolecular interactions

are NH O hydrogen bond generating chains along [010]

(Fig. 4c) and a CH F intermolecular interaction further

stabilizing the crystal structure.

3.4. Structure of (3-chloro-N-(4-methylphenyl) benzamide)

Compound 4 crystallizes in the space group C2=c with

Z 8 showing no orientational disorder or concomitance.This structure is stabilized once again by a strong NH O

hydrogen bond resulting in chains along [010] and a

significantly short Cl Cl contact (Table 3, Fig. 4d). Table 2

provides the most significant dihedral angles, which in

compound 4, are similar to those of compound 3.

4. Discussion

The four crystal structures indicate that in substituted

benzanilides intermolecular hydrogen bonds play a crucial

role in the packing of the molecules. Also these interactions

ensure the absence of orientational disorder and formation

of concomitant polymorphism unlike in the case of the

parent compound [30,31]. The presence of OH O

{Etters symbol [39]: R2216} and NH O {C(4)}hydrogen bonds in the structures of 1 and 2 lead to motifs

(Fig. 3a and b), which completely avoid orientational

disorder in the molecular structure. In structures 1 and 2 an

additional CH O {R2218} provides additional stabilityto the dimer formed by OH O hydrogen bond. Also in

the solvent system (ethyl acetate/hexane) the crystals are

well grown as plates and do not indicate any concomitance.

The formation of dimeric units across the center of

symmetry involving OH O hydrogen bonds in com-

pounds 1 and 2 appear to rule out any short interactions

involving halogens. The halogen interactions CH F

{C(4)} in compound 3 and Cl Cl in compound 4 appear to

render the conformation in these two structures to be similar

to those of the parent compound (Table 3). However, it is of

interest to note that the interactions involving halogens do

remove orientational disorder and form clear plate like

Table 3

Intermolecular interactions

DX A r(DX) (A) r(X A) (A) r(D A) (A) /DX A (8)

Compound 1 N1H1N O10 0.88(2) 2.32(2) 3.087(2) 146.03(2)O2H2O O10 0.86(2) 1.95(2) 2.784(1) 162.83(2)C7H7 O20 0.97(2) 2.47(2) 3.403(2) 162.75(2)

Compound 2 N1H1N O10 0.79(2) 2.29(2) 2.987(2) 149.07(2)O2H2O O10 0.85(3) 1.95(3) 2.774(2) 167.09(3)C7H7 O20 0.93(2) 2.46(2) 3.361(2) 164.96(2)

Compound 3 N1H1N O10 0.85(2) 2.36(2) 3.203(2) 169.32(2)C5H5 F10 0.96(3) 2.68(3) 3.525(3) 147.96(2)

Compound 4 N1H1N O10 0.81(3) 2.58(3) 3.349(3) 160.73(2)C4Cl1 Cl10 1.739(3) 3.29(1) 4.977(3) 162.59(4)

Benzanilide polymorph 1a NH O0 1.15a 2.03a 3.112(6) 157a

Benzanilide polymorph 2b NH O0 0.88b 2.31 3.141(4) 157

a No e.s.ds reported in Polymorph 1 [30].b Hydrogen was fixed in Polymorph 2 [31].


Fig. 4. (a) Packing diagram of Compound 1 showing OH O, CH O dimers and NH O chains in the crystal lattice. (b) Packing diagram of Compound

2 showing OH O, CH O dimers and NH O chains in the crystal lattice. (c) Packing diagram of Compound 3 showing the NH O chains running

parallel to crystallographic b axis and weak CH F interactions. (d) Packing diagram of Compound 4 showing NH O chains running parallel to

crystallographic b axis as well as Cl Cl interaction across the center of symmetry.


crystals indicating no concomitant polymorphism in the

solvent system used.

5. Conclusion

Halogen substituted benzanilides yield crystals with

well-defined hydrogen bonds forming dimers and chains in

case of structures 1 and 2 and exclusively chains in

structures of 3 and 4. The disorder in the parent compound

disappears in structures 1 and 2 by the influence of the

OH O hydrogen bond forming dimeric units across the

center of symmetry. Further, the presence of CH O

interactions in these two compounds does not allow any

disorder. It is to be noted that the involvement of weak

Fig. 4 (continued )


interactions generated by halogens appear in structures 3

and 4 and remove the orientational disorder which

dominates the parent compound. It is of interest to note

that the halogens F and Cl in structures 1 and 2 are ignored

due to the formation of the dimeric moiety forming a strong

OH O hydrogen bond, an observation that might have

significance in crystal engineering of compounds containing

halogens.

6. Supplementary material

Crystallographic details (excluding structure factors) on

the structure analysis of the Compounds 14 reported in this

paper have been deposited with the Cambridge Crystal-

lographic Data Center,12 Union Road,Cambridge,CB2,1E-

Z,UK; (Fax: 44-1223-336-033; e-mail:[email protected]).The depository numbers are given in the tables.

Acknowledgements

We thank Mr Kabirul Islam for assistance during the

synthesis and Prof G. Mehta for kindly allowing use of

laboratory facilities. We also thank IRHPA-DST for

providing the CCD facility at IISc, Bangalore.

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mailto:[email protected]:[email protected]

Analysis of intermolecular interactions involving halogens in substituted benzanilidesIntroductionExperimentalSynthesisX-ray diffraction

ResultsStructure of (3-fluoro-N-(3-hydroxyphenyl)benzamide)Structure of (3-chloro-N-(3-hydroxyphenyl)benzamide)Structure of (3-fluoro-N-(4-methylphenyl)benzamide)Structure of (3-chloro-N-(4-methylphenyl) benzamide)

DiscussionConclusionSupplementary materialAcknowledgementsReferences

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