CHAPTER Iv

CRYSTAL STRUCTURE OF 1,7-BIS(4- CHLOR0PHENYL)-4-(1,3-DITHIOLAN-2-

YL1DENE)-1,6-HEPTADIENE-3,5-DIONE AND 1,7- BIS(4-METH0XYPHENYL)-4-(1,3-DITHIOLAN-2-

YL1DENE)-1,6-HEPTADIENE-3,5-DIONE.

4.1 Introduction

The title compounds were investigated as a link in the systematic

structural studies of curcumin analogues. In spite of the fact that most of the

curcumin analogues reported in this thesis are configurationally symmetric

about the middle atoms, 1,7-bis(4-chloropheny1)-4-(1,3-dithiolan-2-ylidene)-

1,6-heptadiene-3,s-dione (Compound 111) alone retains the two fold axis in the

crystal phase. A para methoxy substitution in the phenyl ring instead of

parachloro substitution in compound 111 gave 1,7-bis(4-methoxypheny1)-4-(1,3-

dithiolan-2-y1idene)- 1,6-heptadiene-3,5-dione (Compound IV).

X=CI (Compound 111)

X=OCH, (Compound IV)

4.2 Synthesis

a) Sodium metal (0.45g, 20mmol) was dissolved in ethanol (20ml) to which

cyclic diacetyl ketenedithioacetal (1.01g, Smmol). was added followed by

para-chloro benzaldehyde (10mmol). The reaction mixture was stirred at O-

5°C for 4 hours. The solid obtained was filtered, washed in ethanol and

recrystallized from a mixture of hexane and ethyl acetate to give compound

111.

b) An analogous condensation process with cyclic ketene dithioacetal and

para-methoxy benzaldehyde gave compound IV.

4.3 Crystallization and Data collection

Needle shaped yellow crystals of compound I11 were obtained from a

solution of methanol-chloroform by slow evaporation and light brown prismatic

crystals of compound IV were obtained from acetone-ethyl acetate solution.

The dimensions of the crystal used for data collection were 0.2 x 0.2 x O.lmm

for 111 and 0.12 x 0.18 x 0.18mm for compound IV. The crystals of compound

111 belong to the monoclinic space group C2/c with unit cell parameters

a=19.203(1)A, b=13.147(1)A, c=8.801(1)A, P=112.99(1)". Compound IV

crystallized in the monoclinic space group P21 with unit cell parameters

a=14.207A, b=7.752(1)A, c=19.473(1)A, P=91.00(3)". The intensity data were

collected up to 28max of 139.8" for I11 and 139.78" for IV by an Enraf-Nonius

CAD-4 diffractometer using crystal monochromated CuKa radiation (A =

1.541 8A). 0-28 scan mode was used for both crystals. The usual precaution of

checking the consistency of the intensities of three strong reflections

periodically (every one hour) for monitoring the stability of the crystal during

x-ray exposure was observed. The intensities were corrected for Lorentz,

polarization and absorption.

4.4 Structure solution and Refinement

Compound I11

The structure was solved by Direct methods using SHELXS-

97[Sheldrick 19971 and all the non-hydrogen atoms were located from the E-

map. The structure was refined using SHELXL-97 [Sheldrick 19971. All

hydrogen atoms were fixed by the program. Anisotropic refinement of the non-

hydrogen atoms along with isotropic refinement of the hydrogen atoms using

1640 reflections with I>2sigma(I) converged the R-factor to 0.0487.

The weighting scheme used was

W = l l [ ~ ~ 2 ~ ( F o " 2 ~ ) + (0.0996P)"2" + 1.3025Pl where P=(FoA2ht 2FcA2")/3

The refinement was continued until the maximum shiftle.s.d is < 0.002. The

final difference map was featureless with maximum and minimum electron

densities at 0.304 and -0.310 eA", respectively.

Compound IV

The structure of this compound also was solved by direct methods using

SHELXS-97[sheldrick 19971 and all the non-hydrogen atoms were located from

the E-map. The structure was refined using SHELXL-97[Sheldrick 19971. All

the hydrogen atoms were fixed by the program. Arlisotropic refinement of the

non-hydrogen atoms along with isotropic refinement of the hydrogen atoms

using 3708 reflections with I>2sigma(I) converged the R-factor to 0.0445.

The weighting scheme used was

W = 1/[sA2A(FoA2A) + (0.0843P)"2" + 0.43Pl where P = ( F o " ~ ~ + 2FcA2")/3

The refinement was continued until the shift/e.s.d is < 0.002. The final

difference map was featureless with maximum and minimum electron densities

at 0.457 and -0.226 eA3 respectively.

4.5 Results

The crystal data and structure solution details of 111 and IV are given in

tables 4.1.1 and 4.2.1. The fractional atomic coordinates with equivalent

isotropic temperature factors are listed in tables 4.1.2 and 4.2.2. The

anisotropic thermal parameters for the non-hydrogen atoms of 111 and IV are

given in tables 4.1.3 and 4.2.3 respectively. The bond lengths are listed in

4.1.4 and 4.2.4 and bond angles for the non-hydrogen atoms are listed in tables

4.1.5 and 4.2.5. The torsion angles involving non-hydrogen atoms are given in

tables 4.1.6 and 4.2.6. Hydrogen atom coordinates are given in tables 4.1.7 and

4.2.7. Tables 4.1.8 and 4.2.8 show the least -squares planes and the deviation

of the relevant atoms from the respective planes for compounds I11 and IV

respectively. Fo-Fc tables for 111 and IV are given in appendices C and D.

Figs. 4.1.1 and 4.2.1 show the perspective view of the molecules drawn

by the program ORTEP [Zsolnai 19971 for compounds 111 and IV, respectively.

Figs. 4.1.2, 4.1.3 and 4.1.4. show the packing of the molecules in the unit cell

for 111. Packing diagrams of IV are given in Figs. 4.2.2,4.2.3 and 4.2.4.

4.6 Discussion

Although most of the structures reported in this thesis are

configurationally symmetric, none of them except compound 111 show perfect

symmetry in their crystalline form. Both the compounds 111 and IV show 2-fold

symmetry in solution as seen from the NMR spectra [Dhanya 19971. While in

the crystal phase, compound I11 alone retained the two fold axis passing

though the middle atoms C(4)-C(5). The asymmetric unit is half a molecule of

compound 111. A para methoxy substitution instead of the para chloro

substitution in the phenyl rings of compound 111 gives the analogue, compound

IV. Compound IV, though symmetric in solution, is asymmetric in the crystal

with two molecules (IV and IVA) in the asymmetric unit. The absence of

symmetry in the molecule in the crystal forpi may be attributed to the crystal

packing forces.

Comparison of Structural Parameters of I11 and IV.

The bond lengths and angles in compounds I11 and IV are comparable

to those reported in chapter I11 and also for other curcumin analogues [Mostad

et al. 1984; Karlsen et al. 1988; Gorbitz 19931. The C(4)-C(5) bond length in I11

is comparable to the corresponding length in IV [C(4)-C(20)=1.388(6)A] and

IVA [C(4)'-C(20)'=1.386(6)A]. The O(1)-S(1) non-bonded distance in I11 is

2.569A and the corresponding distances in IV and IVA are

O(1)-S(1)=2.592(4) A; O(2)-S(2)=2.576(3) A

O(l)'-S(l)'=2,610(3)A; O(2)'-S(2)'=2.562(3) A

The Phenyl groups

The phenyl plane (C(7)-C(8)-C(9)-C(lO)-C(ll)-C(I2)) and the dithiolan

plane (S(1)-C(5)-S(1)a-C(6)a-C(6)) are making an angle of 32.07" in 111. The

two phenyl rings (C(8)-C(15)-C(16)-C(17)-C(I 8)-C(19) and C(9)-C(10)-C(11)-

C(12)-C(13)-C(14) ) are inclined at an angle of 34.92" and 32.43" with the

dithiolan ring (S(2)-C(20)-S(l)-C(2I)-C22)) in IV and 24.90° and 33.02" in

IVA.

The phenyl rings in both the compounds I11 and IV are planar. The

phenyl ring in compound I11 has bond lengths varying from 1.370(4)A to

1.401(3)8, with an average length of 1.384 A and bond angles varying from

121.7" to 117.8' with an avefage of 120". The chlorine atom lies in the plane

of the phenyl ring as seen from the torsion angle C(8)-C(9)-C(10)-C1

[=179.0(2) 01.

The bond lengths and angles of the two phenyl groups in IV are

comparable to those in IVA. The phenyl ring C(8)-C(15)-C(16)-C(17)-C(18)-

C(19) in VI has bond lengths varying from 1.347A to 1.402A with an average

length of 1.383A and bond angles varying from 116.9" to 122.0" with an

average of 119.98". The bond lengths in the other phenyl ring C(9)-C(10)-

C( Il)-C(12)-C(13)-C(14) vary from 1.363A to 1.401A with an average of

1.380A and the bond angles vary from 117.0" to 122.1" with an average of

119.97". The phenyl ring C(8)'-C(15)'-C(16)'-C(17)'-C(18)'-C(19)' in VIA

has bond lengths ranging from 1.369A to 1.399A with an average of 1.381A

and the bond angles ranging from 116.9' to 122.9' with an average of 120.0".

The bond lengths in the phenyl ring C(9)'-C(I0)'-C(I I)'-C(12)'-C(13)'-C(14)'

of VIA vary from 1.367A to 1.407.A with an average of 1.385A and bond

angles vary from 117.4" to 121.8' with an average of 119.98".

The Methoxy substitutions

The methoxy substitutions in IV and IVA lie close to the plane of the

ring to which they substitute as seen from the torsion angles.

The deviation is largest in the case of the methoxy substitution to the phenyl

ring C(9)-C(I0)-C(I 1)-C(12)-C(13)-C(14) of VI.

The dithiolan rings

The five member ring SI-C(S)-S(l)a-C(6)a-C(6) in 111 is in a distorted

half chair conformation which is twisted on C(6)-C(6)a bond [Brahde 1954;

Schmidt and Tulinsky 19671. The five member rings S(2)-C(20)-S(1)-C(21)-

C(22) in IV and S(2)'-C(20)'-S(l)'-C(2I)'-C(22)' in IVA also have the

distorted half chair conformation which are twisted on C(21)-C(22) and C(21)'-

C(22)' bonds, respectively. A similar conformation is also observed for this

group in the compounds reported in the previous chapter.

Intermolecular interactions and crystal packing

The packing of the rnolecules of compound 111 in the bc, ac and ab

planes are illustrated in figs. 4.1.2, 4.1.3 and 4.1.4 respectively. The molecules

related by the c-glide are arranged to form a layer of molecules almost parallel

to the bc plane (fig.4.1.2). The molecules related by the C-centering form

anothel. layer separated by -9.0 from this layer. There is a probable hydrogen

bonding between the carbon atom in the chlorophenyl ring and carbonyl oxygen

at x,-y,-1/2+z position within a layer. The hydrogen bonding parameters are:

D-H--A Symm H---A D---A D-H-- A

C(8)-H(8)--0(1) x,-y,-li2+z 2.4085 A 3.3272 A 169.44"

The packing of the molecules of compound IV in the bc, ac and ab

planes are shown in figs. 4.2.2, 4.2.3 and 4.2.4 respectively. The two halves of

both the molecules IV and IVA are seen folded parallel to the a-axis and the

two phenyl rings are almost parallel to the ab-plane(fig.4.2.4). The two phenyl

planes make an angle of 30.79" between them in IV and 13.76' in IVA. Along

the b-axis there is probable hydrogen bonding between carbon atom C(21) in

the five member dithiolan ring and carbonyl oxygen O(1)' at the x, -l+y, z

position (fig.4.2.2). Molecules are stacked along the a-direction by probable

hydrogen bonding between carbon atom of the dithiolan ring C(21)' and the

oxygen atom O(4)' of the methoxy group at the symmetry position l+x, y, z

(fig.4.2.4). The hydrogen bonding parameters [Wardell et al. 2000; Gerkin

2000; Steiner 19961 are

D-H--A symm H--A D--- A D-H--A

C(21)-H(21A)-O(1)' x,-l+y,z 2.5036A 3.3738 A 153.45'

C(21)'-H(21C)--0(4)' I +x,y,z 2.4085 A 3.3341 A 150.49'

There are two more significant short contacts in compound IV.

D-.H--.A symm D--A

C(2)'-H(2A)--0(1) X,Y,Z 3.4137A

C(22)-H(22B)--0(3) I+x,Y,z 3.2997A

The increased number of short contacts in comparison with compound 111 may

be a reason for its asymmetry observed in the crystal structure.

Fig. 4.2.1. ORTEP plot for IV.

2 Packing of molecules down a-axis for 111

Fig. 4.1.3. Packing of molecules down b-axis for I11

Fig.4.2.2 Packing of molecules down a-axis for IV

Fig. 4.2

Fig. 4.2.4. Packing of molecules in the ab-plane for IV.

T a b l e 4 . 1 . 1 . C r y s t a l d a t a and s t r u c t u r e r e f i n e m e n t for compound 111.

Empirical formula C 2 ~ H16 Cl2 0 2 S2

Formula weight 447.37

Temperature 293(2) K

Wavelength 1.54180 A

Crystal system, space group Monoclinic, C2/c

Unit cell dimensions a =19.2030(10)A alpha= 90.00(2)0. b =13.1470(10)A beta= 112.990(10)0. c =8.8010(10)A gamma= 90.000(10)0.

Volume 2045.4(3) A3

2 , Calculated density 4, 1.453 ~g/m'

Absorption coefficient 4.892 mm-'

F(000) 920

Crystal size 0.2 x 0.2 x 0.1 mm

Theta range for data collection . 4.19 to 69.94".

Index ranges -23<=h<=21, 0<=k<=16, 0<=1<=10

Reflections collected / unique 1871 / 1871 [R(int) = 0.00001

Completeness to 2theta = 69.94 45.9%

Refinement method full-matrix least-squares on F'

Data / restraints / parameters 1871 / 0 / 129

Goodness-of-fit on F- 1.041

Final R indices [1>2sigma(I)] R1 = 0.0487, wR2 = 0.1337

R indices (all data) R1 = 0.0550, wR2 = 0.1444

Extinct.1on coefficient 0.00039(17)

Largest diff. peak and hole 0.304 and -0.310 e. A-3

Table 4.1.2. Atomic coordinates (x104) and equivalent isotropic displacement parameters (AZx103) for compound 111.

Table 4.1.3. Anisotropic displacement parameters (A2x103) for compound 111.

U11 U22 U33 023 U13 U12

51 (I) 59(1) 57(1) 5511) 52(11 5211) 48(2) 51 ( 2 ) 54 ( 2 1 52!l) 5 9 ! 1 ) 60 (2) 53(1) 63 (2) 60(1)

Table 4 . 1 . 4 . Bond lengths [ A ] for compound 111.

Table 4.1.5. Bond angles ['I for compound I11 -.-

S y r n m e ~ r y transformations u s e d t o g e n e r a t e e q u i v a l e n t atoms: # 1 - x i ! , v , - r + l / 2

Table 4.1.6. Torsion angles ['I for compound I11

Symmetry transformations used to generate equivalent atoms: # I -x+1, y, -ztl/2

Table 4.1.7. Hydrogen coordinates (x104) and isotropic displacement parameters (A2x103) for compound 111.

H i l l

H(21

H(6A)

H ( 6 B )

H(81

H ( 9 )

H ( 1 1 )

H(12)

Symmetry transformations used to generate equivalent atoms: #1 -x+l, y , - z + l / 2

Table 4.1.8. Least-squares planes and deviations (A) of relevant atoms from their respective planes.

Eqn. of the plane: 17.7904 (0.0100) x + 0.0000 (0.0001) y - 6.2345 (0.0071) z = 7.3366 (0.0061)

At om S1 C5 Sla C6 C6a

Deviation 0.1320(15) 0.0000(0) -0.1320(15) -0.2809(31) 0.2809(31)

Eqn. of the plane:18.1658 (0.0088) x - 4.1404 (0.0120) y - 2.6281 (0.0098) z = 5.2972 (0.0054)

At om C7 C8 C 9 C10

Deviation 0.0057(16) -0.0025(18) -0.0030(18) 0.0053(18)

Atom Cli C12

Deviation -0.0019118) -0.0036(18)

Table 4.2.1. Crystal data and structure refinement for compound IV.

Empirical formula C24 Hz2 0 4 S2

Formula weight 438.54

Temperature 293(2) K

Wavelength 1.54180 A

Crystal system, space group Monoclinic, PZ1

Unit cell dimensions a = 14.207k alpha = 90.00(2)0. b = 7.7520(10)A beta = 91.00(3)'. c = 19.4730(10)A gamma = 90.00(5)'.

Volume 2144.3(3) A3

2, Calculated density 4, 1.358 ~ q / m ~

Absorption coefficient 2.486 mm-'

F(000) 920

Crystal size 0.12 x 0.18 x 0.18 mm

Theta range for data collection 2.27 to 69.89".

Index ranges 0<=h<=14, 0<=k<=9, -23<=1<=23

Reflections collected / unique 4330 / 4146 [R(int) = 0.01981

Completeness to 2theta = 69.89 94.3%

Refinement method Full-matrix-block least-squares on F2

Data / restraints / parameters 4146 / 1 / 638

Goodness-of-fit on F' 1.144

Final R indices [I>Zsigma(I)] R1 = 0.0445, wR2 = 0.1183

R indices (all data) R1 = 0.0507, wR2 = 0.1274

Absolute structure parameter 0.16(2)

Extinction coefficient 0.0026(4)

Largest diff. peak and hole 0.462 and -0.234 e. A-'

Table 4.2.2. Atomic coordinates ( x l o 4 ) and equivalent isotropic displacement parameters (AZx103) for compound IV.

T a b l e 4 . 2 . 2 . (continued) -. ~

x Y z U (eq)

Table 4.2.3.Anisotropic displacement parameters (A2x1o3) for compound IV.

T a b l e 4 . 2 . 3 . (continued)

Table 4 . 2 . 4 . Bond l e n g t h s [ A ] for compound IV.

Table 4 . 2 . 5 . Bond a n g l e s ["I f o r compound I V .

Table 4.2.6. Torsion angles ["I for compound IV.

T a b l e 4 . 2 . 6 . (continued)

Table 4.2.7. Hydrogen coordinates ( x l o 4 ) and isotropic displacement parameters (AZ x l o 3 ) for compound IV.

Table 4 . 2 . 8 . Least-squares planes and deviations(A) of respective atoms from their respective planes.

Eqn. of the plane: 0.6947 x + 7.7419 y - 0.2964 z = 3.6568

At om C20 S 1 S2 C2 1 C22

Deviation 0.0261 0.1069 -0.1452 -0.2630 0.2752

Eqn. of the plane: 3.0329 x t 7.5729 y - 0.2664 z = 6.3285

At om C20' 51' C21' C22 ' 52'

Deviation 0.0127 0.1307 -0.2892 0.2931 -0.1472

Eqn. of the plane: 2.4870 x + 6.3614 y + 10.5323 z = 8.4560

At om C 8 C15 C16 C17 C18 C19

Deviation 0.0157 -0.0117 0.0003 0.0070 -0.0025 -0.0087

Eqn.of the piane: 2.3879 x + 6.8787 y - 8.4172 z = 4.7217

Atom CA ' C15' C16' C17 ' C18 ' C19'

Deviation 0.0002 0.0095 -0.0139 0.0088 0.0008 -0.0053

Eqn. of the plane: - 4.6544 x + 6.7148 y + 7.4577 z = 2.4782

At om C9 C10 C11 C12 C13 C14

Drvlatlon 0.0001 0.0070 -0.0024 -0.0097 0.0169 -0.0119

Eqn. of the plane: - 0.8670 x + 6.7186 y - 9.6189 z = 3.5867

Atom C9' C10 ' C11' C12 ' C13' C14'

Deviation 0.0025 -0.0106 0.0086 0.0017 -0.0097 0.0075