Furan derivatives of substituted phenylthiourea: Spectral studies, semi-empirical quantum-chemical calculations and X-ray structure analyses

Journal of Molecular Structure 743 (2005) 29–48

www.elsevier.com/locate/molstruc

Furan derivatives of substituted phenylthiourea: spectral studies,

semi-empirical quantum-chemical calculations

and X-ray structure analyses

a,

b

Ol’ga Hritzova , Juraj Cernak , Peter Safar , Zdenka Frohlichova , Ingeborg Csoregh

a

d

ˇ^c

˝

´

˝

ˇ

*

´

a

ˇ

Department of Organic Chemistry, Faculty of Science, Institute of Chemical Sciences, P.J. Safarik University,

´

ˇ

Moyzesova 11, SK-04154 Kosice, Slovak Republic

Department of Inorganic Chemistry, Faculty of Science, Institute of Chemical Sciences, P.J. Safarik University,

b

ˇ

´

ˇ

Moyzesova 11, SK-04154 Kosice, Slovak Republic

^cDepartment of Organic Chemistry, Faculty of Chemical and Food Technology, Slovak Technical University,

´

Radlinskeho 9, SK-81237 Bratislava, Slovak Republic

^dArrhenius Laboratory, Department of Structural Chemistry, Stockholm University, S-106 91 Stockholm, Sweden

Received 24 January 2005; accepted 16 February 2005

Available online 6 April 2005

Abstract

Fifty new derivatives of 1-(furan-2-carbonyl)- and 1-(furan-3-carbonyl)-3-phenyl substituted thiourea have been synthesised and

identiﬁed. Intramolecular hydrogen bonds were investigated in detail, using IR spectroscopy. The three-level Fermi resonance effect in the IR

spectra was analysed after deconvolution and band separation. Semi-empirical quantum-chemical calculations (AM1 and PM3) support the

results of the IR spectroscopic studies. X-ray single crystal diffraction analyses of four selected compounds, namely 1-(furan-3-carbonyl)-3-

(2-triﬂuoromethyl-phenyl)-thiourea (1e), 1-(2-methyl-furan-3-carbonyl)-3-(2-triﬂuoromethyl-phenyl)-thiourea (2e), 1-(2,6-dichloro-

phenyl)-3-(2-methyl-furan-3-carbonyl)-thiourea (2n) and 1-(4-methoxyphenyl)-3-(3-methyl-2-furan-carbonyl)-thiourea (3e), corroborated

the molecular and crystal structure of these compounds. Relatively strong intramolecular hydrogen bonds of the N–H/OaC type as well as

intermolecular two-centred and bifurcated three-centred hydrogen bonds were observed, conﬁrming the results of the IR spectral study and

the semi-empirical quantum-chemical calculations. A variety of intermolecular interactions, yielding the supramolecular architectures in the

four crystalline compounds, are discussed in detail.

Keywords: Thiourea; Hydrogen bonds; Fermi resonance; AM1; PM3; X-ray structure analysis

1. Introduction

organic chemistry concerns interactions among molecules.

Such interactions are governed by intermolecular forces

whose energetic and geometric properties are less well

understood than those of covalent bonds. Conventional

hydrogen bonds (i.e. O–H/O, N–H/O) play a dominating

role among intermolecular interactions due to their strength

and directionality. They are also known to inﬂuence

properties and functions of biologically signiﬁcant sub-

stances, e.g. saccharides, proteins and nucleic acids [5];

hence information about hydrogen bond interactions invol-

ving these molecules has proved to be essential for the

understanding of biochemical processes of vital importance,

such as enzyme–substrate, drug–receptor, and protein–

ligand interactions, among others. Nevertheless, because

recognition as well as packing of molecules is determined

by a sensitive balance of many different intermolecular

Their interesting biological properties, potential for

practical application and availability have considerably

stimulated structure investigation of derivatives of thiourea

[1–3], especially, with respect to their capability of

hydrogen bond formation [4]. Besides an interest in

preparation and properties of individual molecules, an

increasingly signiﬁcant portion of up-to-date research in

*

Corresponding author. Tel.: C421 55 62 281 14; fax: C421 55 62 221

24.

´

E-mail addresses: hritzova@kosice.upjs.sk (O. Hritzova), ics@struc.

˝

su.se (I. Csoregh).

doi:10.1016/j.molstruc.2005.02.014

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

30

forces, a substantial amount of chemical research today is

directed toward increasing the understanding of the nature

and character of weaker interaction forces than those of

classical hydrogen bonds [6,7]. Interactions involving

organic halogens have been discussed in the literature for

some considerable time [8,9]. However, hydrogen bonds,

differing from the conventional X–H/X (XZO, N) case,

such as C–H/O and X–H/p interactions (XZO, N, C)

[10–15], anti-hydrogen bonds [16–18] and the ‘dihydrogen

bond’ X–H/H–M (XZO, N; MZIr, Re) [10] have been

recognized as interactions of chemical relevance only

during the last decade. Moreover, although sulphur, an

important element in biochemistry, can be regarded as a

conventional H-bond acceptor [19], the X–H/S bonds

(XZO, N) are only of moderate strength [20] and together

with the considerably weaker C–H/S interactions are

demanding further evidence. In this connection, investi-

gation of the conditions and requirements of formation of

hydrogen bonds and related intermolecular interactions by

various thiourea derivatives in the solid state may lead to

valuable information about interaction modes between

selected functional groups, on the one hand, and about the

characteristics of this compound family, on the other.

Conventional hydrogen bonds can be detected by

vibrational spectroscopy. In addition, very speciﬁc so-called

resonance phenomena can also be observed in vibrational

spectra, mainly Fermi resonance, which is very important

for analysis of rotation–vibration spectra and correct

interpretation of hydrogen bonds. We encounter it mainly

in polyatomic molecules, if two or three vibrational levels

exhibit the same symmetry and similar energies.

2.2. IR spectroscopy

IR spectra of 1-(furan-2-carbonyl)- and 1-(furan-3-

carbonyl)-3-phenyl thiourea derivatives are shown in

Table 1.

In a detailed study of the IR spectra of these substances,

we observed the absorption bands belonging to the free

amidic NH group, which appear in the 3423–3385.1 cm^K1

region (Table 1). The spectra of all studied compounds

exhibit absorption bands also in the 3238.3–3208.8 cm^K1

region, which we attribute to intramolecular hydrogen

bonding between the hydrogen atom of the thioamidic NH

group and the oxygen atom of the carbonyl group [4,21,22].

The concentration independence of the intensity ratio of

those bands as well as the absence of another band of the

free NH group at low concentrations also indicate that the

compounds occur mostly in the conformation containing

the closed, H-bonded six-membered ring. In addition to the

hydrogen bond indication, we also observed anomalous

splitting of the absorption bands of the thioamidic NH bond

due to Fermi resonance [23,24], with the n(CaC)_arovertone

and the n(CaC)_arCd(NH) combination vibration, so it gives

the interaction for three vibrational levels (Table 1). It is

also well known that Fermi resonance can play a major role

not only in strong hydrogen bonds, but also in relatively

weak hydrogen bonds [25,26]. This implies that, if we want

to assess the hydrogen bond strength, we have to obtain the

wave number of the absorption bands without the inﬂuence

of Fermi resonance, because only such wave numbers will

be dependent solely on the force constant [27]. For this

reason, the relations based on the method of Langseth and

Lord and improved by Nyquist et al. [28] have been applied

in cases involving three-level interactions to enable the

calculation of the wave numbers of the bands, corrected for

Fermi resonance (Table 1). We found that the ﬁrst band in

the Fermi triplet is associated with the branch that, after

elimination of the resonance, belongs to the bonded n(NH)

stretching vibration. The middle branch of the triplet can be

assigned to the ﬁrst overtone n(CaC)_arof the phenyl ring,

and the other side branch of the triplet is connected with the

n(CaC)_arCd(NH) combination vibration. From the unper-

turbed wave number values we calculated the extent of

In accordance with the ideas mentioned above, the aim of

the present investigation has been to contribute to the study

of hydrogen bonds in four series of, mostly novel, 1-(furan-

2-carbonyl)- and 1-(furan-3-carbonyl)-3-phenyl-substituted

thiourea derivatives. These compounds seem to us to be

good model compounds for such a study, because they

contain various heteroatoms and functional groups acces-

sible to formation of hydrogen bonds. We have therefore

studied hydrogen bonding in this class of compounds, using

IR spectroscopy, semi-empirical calculations and X-ray

diffraction analysis.

interaction [28,29] between the absorption band pairs W_AB

W

,

_BC, W_AC(Table 1), and found that the n(NH/OaC)

ground stretching vibration interacts more with the

n(CaC)_arCd(NH) combination vibration than with

the n(CaC)_arovertone in almost all of the compounds.

The very strong absorption bands of the carbonyl stretching

vibrations lie within the 1699.6–1670 cm^K1range for all the

compounds, but the wave numbers are also affected by the

intramolecular NH/OaC hydrogen bonds. The strength of

those hydrogen bonds can be demonstrated by calculating

their force constants [30] from the band positions corrected

for Fermi resonance. For the NH/OaC hydrogen bonds,

the force constants lie within the (5.749–5.654)!10²N m^K1

range. These results could be compared with previous data

2. Results and discussion

2.1. Syntheses

The derivatives of 1-(furan-2-carbonyl)- and 1-(furan-3-

carbonyl)-3-phenyl-substituted thiourea (1a–1n, 2a–2p,

3a–3n, 4a–4f) (Scheme 1) were prepared by reaction of

corresponding furoylisothiocyanates with amines. The

molecular structures of the newly synthesized compounds

were established by IR and NMR spectral methods. The

details are gathered in the experimental part.

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

31

Scheme 1.

[31]. To ﬁnd the inﬂuence of substituents on the hydrogen

2.3. Semi-empirical calculations

bond strength, we utilised the linear correlation between

spectroscopic properties and Hammet’s substituent constants

s_p[32]. Wehavetakenintoconsiderationthewavenumbersof

n(NH)_free, n(CaO) and the unperturbed n⁰_A(NH/OaC) wave

numbers, i.e. those corrected for Fermi resonance. Statistical

results of this correlation are listed in Table 2.

After spectroscopic veriﬁcation of the existence of

relatively strong intramolecular hydrogen bonds in the

studied compounds, we tried to obtain more information

about the most stable conformations of selected molecules.

For such conformational studies, we used the semi-empirical

methods AM1 and PM3. Geometries were completely

optimised, whereupon we carried out the conformational

study. The calculated bond distances and bond angles are

presented in Table 3. (Supplementary Material) for 1-(furan-

2-carbonyl)- and 1-(furan-3-carbonyl)-3-phenyl-thiourea

derivatives. The lengths of hydrogen bonds are in the range

The correlations for free NH groups are statistically most

signiﬁcant for all compounds. Similarly, the unperturbed

wave numbers for bonded NH groups and n(CaO) for 1a–

3n also ﬁt the correlation quite well. In the case of the 4a–4f

compounds, the correlations are less signiﬁcant because of

the very few substances available for investigation. The

correlation includes also a few 2,4- and 3,4-disubstituted

compounds, the s values of which were calculated assuming

additivity of s_pand s_mvalues. The relatively small effect of

ortho and meta-substituents on the strength of intramole-

cular hydrogen bonding can be explained by the non-

planarity of the studied compounds and by the substituted

phenyl ring being turned toward other parts of the molecule.

The deviations in the mentioned dependencies can also be

due to the presence of weak interactions between the solute

molecule and the solvent.

˚

of 1.81–1.84 A for PM3 and 2.05–2.10 A for AM1

calculations. The calculated angles N–H/O are more than

1208 for all compounds. The observed deviation of phenyl

ring is caused by presence of the substituents. The most

signiﬁcant deviation is recognized in derivatives containing

two atoms of chlorine at 2,6 positions of phenyl ring. The

calculated torsion angles for 2,6-dichloro-substituted com-

pounds (1l, 2n, 3k) are around 91.298.

The results obtained from the calculations proved that the

most stable conformation for all derivatives of thiourea

Table 1

IR band positions (cm^K1) of compounds 1a–4f

n(NH)^afree

Fermi triplet parameters^bafter band separation^a

n(CaO)^a

n(NH/OaC),

2n(CaC)_ar

n (CaC)_arCd(NH)

W_AB; W_AC; W_BC

c

v_A⁰

Band I^c

Band II^c

Band III^c

Sum^d

c

n_B⁰

v_C⁰

1a

1b

1c

1d

1e

1f

3415.3 (1.662)

3415.2 (1.800)

3416.0 (1.540)

3415.7 (1.885)

3415.5 (1.684)

3414.1 (1.483)

3413.0 (1.247)

3413.6 (1.578)

3415.7 (0.901)

3414.5 (1.606)

3415.0 (1.615)

3415.7 (1.521)

3414.3 (1.629)

3413.6 (1.134)

3421.2 (1.292)

3421.5 (1.743)

3423.0 (1.682)

3422.2 (1.720)

3422.6 (1.662)

3420.9 (1.742)

3420.2 (1.690)

3422.3 (1.780)

3420.9 (1.555)

3420.2 (1.579)

3421.6 (1.812)

3421.1 (2.051)

3421.1 (1.738)

3422.9 (1.509)

3421.2 (1.970)

3420.5 (1.744)

3400.6 (2.255)

3401.8 (2.176)

3400.9 (1.945)

3398.2 (2.258)

3401.4 (2.129)

3407.6 (2.336)

3400.6 (2.332)

3400.3 (2.178)

3400.2 (2.214)

3400.1 (2.353)

3399.2 (1.948)

3399.0 (2.172)

3234.7 (1.114)

3234.5 (1.545)

3230.7 (1.953)

3234.0 (1.185)

3223.9 (0.509)

3234.3 (0.483)

3233.8 (0.240)

3228.7 (0.166)

3235.1 (1.899)

3237.7 (0.629)

3233.3 (0.762)

3215.7 (1.343)

3229.5 (0.574)

3225.9 (0.382)

3226.1 (0.328)

3224.1 (1.215)

3224.5 (1.551)

3225.4 (0.949)

3215.1 (0.669)

3218.6 (0.424)

3218.7 (0.318)

3227.9 (1.253)

3224.1 (0.641)

3221.1 (0.313)

3227.9 (0.840)

3220.6 (0.742)

3209.7 (0.267)

3208.8 (0.791)

3219.9 (0.933)

3217.2 (0.439)

3232.1 (1.401)

3230.5 (1.899)

3226.7 (1.180)

3230.1 (0.437)

3231.2 (1.543)

3238.3 (0.955)

3231.0 (0.787)

3232.3 (1.083)

3230.3 (0.807)

3227.4 (0.775)

3216.6 (1.297)

3221.2 (0.462)

3185.0 (0.604)

3186.9 (0.624)

3187.3 (0.524)

3187.3 (0.646)

3187.0 (0.481)

3186.9 (0.449)

3165.9 (1.083)

3169.9 (0.653)

3183.8 (1.143)

3177.6 (1.158)

3184.5 (0.682)

3164.1 (1.132)

3171.3 (1.002)

3168.7 (0.665)

3178.2 (0.324)

3171.7 (0.458)

3176.8 (0.583)

3175.8 (0.574)

3171.4 (0.440)

3166.4 (0.737)

3162.3 (0.710)

3169.0 (1.395)

3177.5 (0.486)

3165.8 (0.850)

3182.3 (0.538)

3164.7 (0.943)

3163.8 (0.215)

3173.1 (0.225)

3168.8 (1.021)

3167.2 (0.215)

3182.1 (0.617)

3183.7 (1.015)

3181.2 (0.418)

3184.9 (0.589)

3181.4 (0.815)

3183.4 (0.878)

3183.8 (0.808)

3183.0 (0.655)

3187.1 (0.742)

3185.4 (0.267)

3174.4 (0.697)

3168.1 (0.506)

3151.2 (1.226)

3156.2 (1.484)

3152.8 (1.857)

3154.5 (1.307)

3147.7 (1.464)

3151.3 (1.175)

3136.2 (0.204)

3146.8 (0.380)

3150.5 (1.637)

3143.4 (0.735)

3145.1 (1.272)

3141.6 (0.821)

3147.0 (0.445)

3150.3 (0.221)

3150.2 (0.930)

3144.7 (1.306)

3145.9 (1.649)

3144.8 (1.343)

3136.0 (0.960)

3127.7 (0.362)

3125.1 (0.245)

3129.7 (0.501)

3138.3 (1.352)

3119.2 (0.257)

3146.0 (1.485)

3128.4 (0.794)

3146.8 (0.757)

3148.8 (1.101)

3126.7 (0.855)

3155.4 (0.877)

3151.4 (1.657)

3148.2 (1.358)

3154.0 (1.009)

3143.5 (1.042)

3149.4 (1.077)

3150.1 (0.866)

3143.0 (1.132)

3149.7 (1.126)

3144.8 (1.141)

3155.1 (1.172)

3145.6 (1.238)

3149.4 (0.379)

1677.7 (4.216)

1676.8 (5.179)

1676.4 (4.632)

1677.6 (4.897)

1681.3 (4.073)

1678.2 (4.098)

1679.7 (2.671)

1680.3 (3.752)

1677.0 (2.226)

1679.5 (3.818)

1680.3 (3.883)

1680.0 (5.090)

1679.1 (3.532)

1678.3 (2.524)

1671.7 (3.692)

1671.4 (3.709)

1671.5 (4.069)

1672.3 (3.655)

1675.8 (3.801)

1673.3 (3.489)

1674.4 (3.180)

1671.8 (3.698)

1673.8 (3.213)

1673.4 (2.791)

1672.1 (3.836)

1673.3 (3.817)

1675.7 (3.460)

1675.0 (4.209)

1674.9 (4.001)

1672.9 (3.550)

1670.2 (4.052)

1699.6 (4.529)

1670.1 (3.771)

1672.2 (3.746)

1670.0 (4.013)

1671.3 (4.027)

1673.6 (3.949)

1670.8 (3.941)

1673.3 (4.109)

1671.6 (4.443)

1673.3 (6.246)

1671.5 (3.654)

3202.70

3205.90

3203.97

3203.64

3191.30

3197.69

3187.93

3186.84

3203.69

3196.22

3196.62

3187.26

3193.50

3192.91

3190.85

3193.73

3195.32

3192.43

3183.60

3181.90

3179.82

3193.45

3187.82

3179.73

3194.16

3182.40

3179.28

3185.71

3184.04

3188.28

3200.86

3202.17

3200.95

3192.43

3202.56

3203.37

3195.20

3200.65

3196.52

3199.01

3190.19

3190.54

3186.00

3187.53

3185.39

3187.93

3184.91

3188.34

3180.10

3181.17

3185.36

3184.67

3184.98

3169.90

3180.92

3179.95

3182.09

3174.30

3177.38

3177.98

3171.19

3170.07

3168.62

3173.24

3177.35

3169.71

3182.37

3168.85

3169.98

3173.20

3169.60

3174.63

3183.63

3183.22

3182.01

3184.64

3182.50

3187.15

3183.73

3184.25

3185.38

3185.39

3175.08

3176.26

3192

3224

3192

3220

3200

3248

3192

3208

3240

3160

3192

3184

3176

3192

3176

3184

3192

3168

3192

3176

3192

3232

3160

3208

3184

3192

3200

3208

3184

3200

3182.20

3184.16

3181.44

3184.23

3182.40

3186.47

3167.87

3177.39

3180.35

3177.82

3181.31

3164.24

3173.37

3172.04

3181.55

3172.48

3174.50

3175.58

3167.72

3160.74

3157.65

3159.92

3174.73

3156.67

3179.67

3162.46

3171.05

3171.79

3161.76

3176.90

3181.11

3177.01

3178.94

3181.43

3176.95

3181.28

3178.87

3180.10

3180.31

3183.51

3171.33

3171.90

3140

3144

3156

3140

3150

3152

3148

3172

3140

3148

3172

3124

3140

3136

3144

3124

3132

3112

3124

3144

3140

3124

3148

3120

3140

3124

3128

3168

3116

3140

3136

3120

3140

3132

3144

3148

3152

3140

3132

3144

11.05; 22.48; 4.86

10.32; 22.26; 4.17

8.08; 22.87; 4.63

10.41; 21.34; 4.82

4.70; 16.12; 3.74

7.21; 18.67; 2.77

17.59; 11.33; 17.58

12.01; 12.46; 7.30

13.59; 22.32; 6.53

16.45; 18.24; 10.59

9.79; 20.87; 5.33

16.38; 17.29; 7.38

17.61; 15.10; 10.66

18.08; 12.74; 10.51

6.70; 16.74; 0.81

10.17; 23.06; 2.24

9.40; 22.47; 3.54

9.66; 21.14; 3.21

8.76; 20.06; 4.71

16.50; 17.02; 13.44

17.80; 15.32; 15.53

22.35; 18.08; 16.51

7.29; 20.21; 3.69

17.59; 15.72; 18.74

7.69; 20.40; 3.66

15.59; 20.10; 9.39

6.10; 14.75; 1.53

5.10; 17.11; 1.67

15.41; 20.81; 11.07

7.09; 16.94; 2.92

9.75; 22.55; 3.17

13.41; 21.77; 7.87

10.04; 21.21; 3.72

7.99; 18.01; 5.22

14.14; 21.87; 7.01

15.58; 21.00; 8.12

10.99; 20.31; 7.18

11.78; 21.83; 5.48

9.94; 20.10; 7.33

6.12; 19.94; 2.28

10.23; 19.18; 4.84

15.38; 16.20; 6.06

1g

1h

1i

1j

1k

1l

1m

1n

2a

2b

2c

2d

2e

2f

2g

2h

2i

2j

2k

2l

2m

2n

2o

2p

3a

3b

3c

3d

3e

3f

3g

3h

3i

3j

3k

3l

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

33

comprises a six-membered ring with perturbed planarity,

closed via an intramolecular N–H/OaC bond. This result

is in line with the conclusions drawn from the analyses of

the IR spectra.

2.4. X-ray structure analysis

X-ray diffraction analyses of four selected carbonyl-

thiourea derivatives, namely 1e, 2e, 2n, and 3e (Scheme 1),

were carried out in order (1) to get information about the

solid-state conformation of these molecules, (2) to obtain

direct structural evidence for the assumed intramolecular

hydrogen bonds in the present compound families, and (3)

to learn about molecular interactions modes and their

variation in four closely related crystalline compounds.

Moreover, our aim was also to compare the results of the

X-ray structure analyses with those of the spectroscopic

studies and quantum-chemical calculations. The selection of

the four derivatives (i.e. 1e, 2e, 2n, and 3e) was mainly

directed by the ability of the compounds to form crystals

suitable for single-crystal X-ray diffraction study (Table 4).

2.4.1. Molecular conformations

The results of the X-ray structure analyses conﬁrmed the

important common feature of the investigated thiourea

derivatives, that is the relatively strong intramolecular

(N–)H/O(aC) hydrogen bond (Fig. 1(a)–(e), Table 5),

which leads to the formation of a six-membered closed loop

with the graph-set notation S(6) [33–35]. Creation of this

(pseudo) ring is crucial for the molecular conformations,

because it prevents free rotation within the central carbonyl-

thiourea moiety and locks its atoms in a nearly planar

arrangement (Table 6).

The 1-(furan-3-carbonyl)-thiourea derivatives, such as

1e, 2e (molecules A and B) and 2n (molecules A, B, C and

D), exhibit similar conformations, as seen in Fig. 1(a)–(d).

The plane deﬁned by the O(6)–C(6)–N(7)–C(8)–S(8)–N(9)

atoms [i.e. the non-hydrogen atoms of the carbonylthiourea

moiety] (plane 1) is only slightly tilted with respect to the

furan ring plane (plane 2), but roughly perpendicular to the

plane of the phenyl ring (plane 3) in these compounds.

Accordingly, the dihedral angles formed by the least-

squares (LS) planes 1 and 2 in compounds 1e, 2e and 2n (i.e.

in seven crystallographically independent molecules) range

between 11.1 and 18.68 with the mean value 14 [3]8 (the

dispersion around the arithmetic average is given in angular

brackets), and the dihedral angles between LS planes 1 and

3 have the mean value 828 [5]8, and vary from 75.5 to 87.88.

The conformation of molecule 3e (Fig. 1(e)) is different,

however. The backbone of this molecule is somewhat

curved, with the furan and the phenyl ring (LS) planes

slightly tilted with respect to the central plane deﬁned by the

O(6)–C(6)–N(7)–C(8)–S(8)–N(9) atoms, thus, yielding

the dihedral angles 5.2(2) and 16.7(2)8, respectively. The

obvious reason for the observed differences in

the orientation of the phenyl ring is the presence of

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

34

Table 2

Linear correlations for compounds 1–4 (yZaCbx)

y

x

n^a

r^b

s^c

a

b

1

2

3

4

n(NH)_free

v⁰_A(NH/OaC)

n(CaO)

s_p

9

0.951

0.940

0.945

0.927

0.914

0.907

0.959

0.921

0.970

0.948

0.860

0.588

0.34

2.32

0.42

0.33

2.28

0.46

0.32

1.70

0.21

0.29

3.78

1.07

3415.0

3199.8

1677.8

3421.6

3189.8

1672.4

3400.4

3198.9

1670.6

3399.1

3200.3

1672.1

K3.15

K19.31

3.67

9

n(NH)_free

v⁰_A(NH/OaC)^d

11

10

11

4

K2.68

K16.13

3.20

n(CaO)^e

n(NH)_free

f

K3.46

K12.78

2.56

n⁰_A(NH/OaC)^f

n(CaO)^g

n(NH)_free

K2.62

K19.14

2.33

v⁰_A(NH/OaC)

n(CaO)

4

a

b

c

d

e

f

Number of compounds used in the correlation.

Correlation coefﬁcient.

Standard deviation.

Compound 2k omitted.

Compound 2o omitted.

Compound 3f omitted.

Compound 3i omitted.

g

the ortho-phenyl substituent(s), such as CF₃in 1e and 2e,

and the two Cl substituents in each of the four molecules of

2n, whose space requirements force the respective phenyl

ring out of the plane of the thiourea moiety. The methoxy

group linked to the phenyl ring in 3e, however, does not

have the same effect because of its para position. In

addition, the moderately twisted attachment of the phenyl

ring to the thiourea moiety in the crystalline 3e derivative

opens a possibility for an intramolecular approach between

the aryl C(15)–H and the thio [S(aC)] group (Table 5).

Although C–H/S bonds are supposed to be very weak, a

comparison with the literature [36] suggests that this

interaction may contribute to the stabilization of the solid-

state conformation of the 3e molecule. The furan ring, on

the other hand, seems to prefer an orientation roughly co-

planar with the central carbonyl-thiourea moiety in all four

studied compounds. The o-methyl substituent on the furan

ring in compounds 2e, 2n and 3e does not counteract this

conformation. On the contrary, the observed conformation

is possibly stabilized by a (C_methyl–)H/O(aC) intramole-

cular bond from the o-methyl substituent of the furan ring to

the exa-cyclic carbonyl oxygen in each molecule (Fig. 1(b)–

(e); Table 5). Even if this latter interaction is certainly rather

weak, the repeated appearance of the same interaction

pattern in seven crystallographically independent molecules

in three different crystal structures suggests that these bonds

have chemical relevance and may contribute to the

determination of the orientation of the furan ring in each

of the derivatives 2e, 2n and 3e.

The observed [K3.75(4)8] and calculated (K11.718) values

of t₂, deﬁned by atoms N(7)–C(6)–C(3)–C(4), are also

somewhat different in 1e. Such differences may be the

consequence of crystal packing forces (see below). At

the same time, according to the X-ray investigations, t₁has

the values 83.8(2) and 80.1(2)8 for molecules A and B in 2e,

and 92.1(4), K90.4(4), 92.2(4) and K93.8(4)8 for mol-

ecules A, B, C, and D in 2n. The calculated value of t₁for

the latter compound is 91.298, which agrees very well with

92 [1.4]8, the mean value of the dihedral angles from the

X-ray study. The different orientation of the phenyl ring in

3e, as compared with that in the previous three compounds,

is obvious from both the X-ray structure analysis [t₁Z

21.5(4)8] and the theoretical calculations (t₁Z26.658),

although the observed and calculated values of t₁differ

somewhat.

The torsion angle t₃, deﬁned by atoms C(2)–C(3)–C(6)–

O(6) (Fig. 1(a)–(d)), gives information about the orientation

of the furan ring in relation to the carbonyl group and the

central carbonylthiourea moiety. According to the X-ray

investigations, t₃, has the values K9.9(3)8 in 1e, 5.3(3) and

K4.5(3)8 for molecules A and B in 2e, and K11.3(4),

2.2(5), 9.5(5), K12.4(5)8 for molecules A, B, C, and D in

2n, respectively. The corresponding angle in 3e (t₄), deﬁned

by C(3)–C(2)–C(6)–O(6) (Fig. 1(e)), has the value 3.1(4)8

according to the X-ray study, whereas the theoretical

calculations yielded the value 1.618. We can see from

these results, and also from the comparison of the

observations in crystallographically independent molecules

(e.g. A and B in 2e, and A, B, C, and D in 2n), that crystal

packing forces give rise to larger variations in the

orientation of the furan ring than the presence or absence

of the 2-methyl (in 2e and 2n) or 3-methyl substituent (in

3e) (see also the following discussion of intermolecular

interactions).

The solid-state conformations, deduced from the X-ray

diffraction analyses, are generally in agreement with the

results of the quantum-chemical calculations. However, in

1e the torsion angle t₁, deﬁned by atoms C(8)–N(9)–C(10)–

C(15), has the observed (X-ray) value 74.85(3)8, whereas

the calculations yielded 82.648 for the same angle.

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

35

Table 3

Geometrical parameters of hydrogen bonds computed by AM1 a PM3

Table 3 (continued)

˚

d(NH) (A)

˚

d (H/O) (A) d (N/O) (A) : (8)

˚

d(NH) (A)

˚ ˚

d (H/O) (A) d (N/O) (A) : (8)

3b

3c

3d

3e

3f

1.01

1.02

1.01

1.00

1.01

1.00

1.01

1.02

1.01

2.07

1.82

2.07

1.81

2.05

1.82

2.07

1.82

2.06

1.82

2.07

1.82

2.06

1.82

2.07

1.81

2.05

1.81

2.10

1.84

2.06

1.82

2.05

1.82

2.05

1.82

2.07

1.83

2.07

1.82

2.08

1.82

2.07

1.82

2.06

1.82

2.07

1.82

2.799

2.630

2.798

2.621

2.794

2.620

2.796

2.624

2.793

2.620

2.795

2.624

2.795

2.622

2.793

2.621

2.797

2.620

2.786

2.606

2.793

2.620

2.797

2.622

2.798

2.622

2.803

2.631

2.797

2.626

2.800

2.633

2.799

2.629

2.803

2.630

2.798

2.629

127.2

134.2

127.6

133.4

128.4

133.5

127.1

133.6

127.9

133.5

126.6

133.9

127.5

133.5

126.6

133.7

128.8

133.4

123.8

130.2

127.7

133.5

128.8

133.6

128.8

133.6

127.6

133.8

127.4

133.7

126.5

134.2

127.5

133.8

128.4

134.0

127.7

133.8

1a

1b

1c

1d

1e

1f

1.01

1.02

1.01

1.02

1.01

1.02

1.00

1.01

1.02

1.01

1.00

1.01

1.02

1.01

1.02

1.01

1.00

1.01

1.00

1.01

1.02

1.01

1.02

1.01

1.02

1.01

1.02

1.01

1.02

1.01

1.02

1.00

1.01

1.02

1.01

1.02

1.01

2.07

1.82

2.07

1.82

2.07

1.83

2.07

1.82

2.07

1.82

2.06

1.82

2.05

1.82

2.06

1.82

2.08

1.83

2.06

1.82

2.08

1.82

2.10

1.84

2.06

1.82

2.06

1.82

2.06

1.82

2.06

1.82

2.07

1.82

2.06

1.82

2.07

1.84

2.06

1.82

2.05

1.82

2.07

1.82

2.06

1.82

2.07

1.82

2.06

1.82

2.06

1.82

2.07

1.82

2.09

1.83

2.06

1.82

2.06

1.82

2.07

1.82

2.797

2.630

2.797

2.631

2.796

2.637

2.800

2.631

2.624

2.796

2.794

2.625

2.794

2.626

2.788

2.621

2.796

2.630

2.791

2.627

2.794

2.631

2.786

2.606

2.796

2.629

2.796

2.907

2.792

2.629

2.789

2.630

2.791

2.636

2.792

2.630

2.694

2.794

2.785

2.624

2.787

2.625

2.790

2.629

2.788

2.626

2.789

2.630

2.789

2.627

2.789

2.628

2.789

2.629

2.610

2.781

2.789

2.628

2.789

2.628

2.798

2.624

127.3

133.9

127.3

133.9

126.9

134.5

127.7

133.9

126.5

133.3

127.3

133.7

128.5

133.9

127.1

133.5

126.9

133.9

127.6

133.8

126.4

134.2

123.6

130.2

127.7

133.9

128.0

133.9

127.5

133.9

127.6

133.9

126.9

134.5

128.4

133.9

126.8

127.5

127.2

133.8

128.3

133.9

127.1

133.8

127.7

133.9

126.5

134.3

127.3

133.9

127.6

133.9

126.4

133.8

131.2

128.6

127.8

133.9

127.8

133.9

127.6

133.6

3g

3h

3i

1g

1h

1i

3j

3k

3l

1j

1k

1l

3m

3n

4a

4b

4c

4d

4e

4f

1m

1n

2a

2b

2c

2d

2e

2f

!

AM1

PM3

2g

2h

2i

2.4.2. Intermolecular interactions and packing relations

The selected four carbonylthiourea derivatives, namely

1e, 2e, 2n and 3e, differ only in the type and position of the

substituent(s) connected to the terminal phenyl and/or furan

rings. Hence, the size and overall shape of the molecules in

the studied crystals differ only slightly from each other.

However, due to the presence of a number of polar groups in

the molecules, the more or less directional intermolecular

interactions rather than shape recognition have been

expected to play the leading role in the crystallization

processes. Indeed, the closely related derivatives were

found to exhibit various molecular recognition modes,

utilizing a wide variety of non-covalent interactions in the

formation of endless supramolecules in their crystals.

Besides the intramolecular (N–)H/O(aC) bond in

compound 1e (Fig. 1(a)), there are also intermolecular

interactions, although considerably weaker, involving

2j

2k

2l

2m

2n

2o

2p

3a

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

36

Table 4

Summary of crystal data, experimental parameters and selected details of the reﬁnement calculations in the X-ray diffraction analysis of compounds 1e, 2e, 2n

and 3e

1e

2e

2n

3e

CCDC deposition number

Empirical formula (sum)

Empirical formula (moiety)

240290

240,291

240,292

240,293

C₁₃H₉F₃N₂O₂S

C₂₈H₂₂F₆N₄O₄S₂

2(C₁₄H₁₁F₃N₂O₂S)

C₅₆H₅₂Cl₈N₈O₁₀S₄

4(C₁₃H₁₀Cl₂N₂O₂S)

2(C₂H₆O)

1408.90

C₁₄H₁₄N₂O₃S

Formula weight

Crystal system

Space group

314.28

656.62

290.33

Triclinic

PK1

Triclinic

PK1

Monoclinic

Cc

Monoclinic

P 2₁/c

˚

a (A)

˚

b (A)

˚

c (A)

8.152(2)

8.219(2)

10.618(2)

99.56(2)

105.74(2)

95.91(2)

2

8.1760(10)

11.838(2)

15.314(3)

95.50(2)

103.48(2)

95.43(2)

2

27.266(3)

13.3150(10)

19.509(2)

90

11.8480(10)

8.7450(10)

13.5750(10)

90

a (8)

b (8)

g (8)

Z

110.482(12)

90

90.366(12)

90

4

3

˚

V (A )

667.0(3)

1.565

1424.2(4)

1.531

6634.9(11)

1.410

1406.5(2)

1.371

D

_calc,X-ray(mg m^K3

)

˚

Radiation/wavelength (A)

Mo K_a/0.71073

0.284

Mo K_a/0.71073

0.269

Mo K_a/0.71073

0.525

Mo K_a/0.71073

0.238

m_X-ray(mm^K1

)

F(000)

320

672

2896

608

Crystal size (mm)

Crystal shape/colour

Index ranges h,k,l

0.15!0.30!0.40

Irregular/colourless

K9!h!9, K10!k!10,

K12!l!13

8657

0.07!0.25!0.25

Plate/colourless

K10!h!10, K14!k!

14, K18!l!18

19036

0.25!0.30!0.33

Plate/colourless

K33!h!33,K16!k!

16, K23!l!23

28,161

0.10!0.14!0.35

Needle/colourless

K14!h!13, K10!k!

10, K16!l!15

9636

Reﬂections collected

Independent reﬂections

R_int

2375

4064

12,414

2676

0.043

0.053

0.048

0.066

Reﬂections with FO4s(F)

Parameters reﬁned

R₁for FO4s(F)

2009

3172

10195

1852

199

421

845

197

0.044

0.041

0.040

0.064

a

wR₂for all unique F²

0.123

0.117

0.104

0.144

S (Goodness-of-ﬁt on F²)

1.082

1.090

1.006

1.053

Final shift/esd, mean/max

0.000/0.001

0.37/K0.33

0.000/0.005

0.24/K0.22

0.004/0.118

0.58/K0.65

0.000/0.001

0.23/K0.39

Residual electron density,

3

max/min (e^K/A )

˚

a

The weights of the F²values were calculated as [s²(F²)C(c₁$P)²Cc₂$P]^K1where PZ(F²₀C2F²_c)/3, and the constants, c₁and c₂have the values 0.077 and

0.110 for 1e, 0.066 and 0.250 for 2e, 0.066 and 0.0 for 2n, and 0.073 and 0.300 for 3e.

the same imino and carbonyl groups of nearest neighbouring

molecules (Table 5). As a consequence, each N(9)–H group

functions as a donor group in a bifurcated hydrogen bond,

and each O(6) carbonyl oxygen accepts two H-bonds, one

intra- and one intermolecular. In this way, an unusual four-

membered closed loop is created through four non-covalent

H/O interactions, which connects two adjacent, centro-

symmetrically related molecules into dimers (Fig. 2).

Formation of the closed loop leads also to a relatively

different conformations (Table 6), most probably due to

anisotropic crystal packing forces. Inspection of the

intermolecular contact distances indicates a non-covalent

carbonyl–carbonyl (i.e. dipole–dipole) interaction between

centrosymmetrically related A molecules [C/OZ

˚

3.443(3) A], and a tendency to similar approach between

˚

corresponding B molecules [C/OZ3.754(3) A]. In the

course of a systematic database analysis of the geometries of

carbonyl–carbonyl interactions, Allen et al. [37] identiﬁed

three distinct CaO/CaO contact patterns in crystals: the

antiparallel, the perpendicular, and the sheared parallel

motifs. Geometries of the CaO/CaO connections in 2e

conform to that of the most frequently occurring antiparallel

motif. Because the interacting keto groups in 2e are related

by a centre of symmetry, the CaO/CaO torsion angle is

restricted to 08 in both interactions. The unique CaO/C

(A₁) and O/CaO (A₂) angles, respectively, have the

values 80.11(11) and 99.89(12)8 in the A dimer, and

63.95(13) and 116.05(13)8 in the dimer of B molecules. Our

observations are in accordance with those of the database

˚

short intermolecular contact distance of 2.954(3) A between

the two carbonyl oxygen atoms in the four-membered ring.

A pair of (C–)H/S interactions [19,36] link the dimeric

units of the 1e derivative into inﬁnite, parallel ribbons along

the crystallographic c-axis. The packing of the ribbons

seems to be directed by the space requirement of the

protruding CF₃groups, besides the common van der Waals’

forces (Table 5).

Crystals of the 2e derivative contain two symmetry

independent (i.e. crystallographically unique) molecules,

molecules A and B (Fig. 1(b)), which exhibit slightly

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

37

(a)

(c)

(b)

(d)

(e)

Fig. 1. Perspective view of the 1e (a) derivative, the two independent molecules of 2e (b), the two unique H-bonded 2n$ethanol (2:1) associates (c, d), and the

3e molecule (e), respectively. The atomic displacement ellipsoids of the non-hydrogen atoms and disorder sites, shown with crystallographic labelling, are

drawn at 30% probability level. Broken lines represent possible hydrogen bond interactions.

analysis by Allen et al. [37], which indicated that

˚

interaction is comparable to that of a medium-strength

hydrogen bond, even at longer distances [37]. Conse-

quently, it is reasonable to suggest that the observed CaO/

CaO interactions in 2e, also that between the B molecules,

may play an important role in the supramolecular

recognition processes. The A/A and B/B associates,

interactions with longer C/O distance [d(C/O)O3.6 A]

tend to have angle values that deviate considerably from the

most probable values, namely 83.58 for A₁and 96.58 for A₂.

At the same time, ab initio molecular-orbital calculations

indicated that the strength of the carbonyl dipole–dipole

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

38

Table 5

˚

Distances (A) and angles (8) in possible intra- and intermolecular hydrogen bond interactions, and selected intermolecular contact distances, observed in

compounds 1e, 2e, 2n and 3e

˚

Distance D–H (A)

˚

Distance H$$A (A)

Atoms involved

Symmetry

Distance D/A (A)

Angle :D–H$$A (8)

1e

N(9)–H(9N)/O(6)

C(4)–H(4)/S(8)

O(6)/O(6)

F(1)/F(1)

F(1)/F(3)

F(1)/O(6)

F(1)/C(5)

F(3)/C(6)

x, y, z

2.634(2)

3.257(2)

3.539(3)

2.954(3)

3.029(4)

3.201(3)

3.248(3)

3.311(4)

3.254(3)

0.96

0.93

1.89

2.44

2.62

133

143

168

KxC1, KyC1, KzC2

Kx, KyC1, KzC1

KxC1, KyC1, KzC2

KxC1, Ky, KzC2

KxC1, KyC1, KzC2

Kx,KyC1, KzC2

x, yK1, z

2e

N(9A)–H(9NA)/O(6A)

N(9B)–H(9NB)/O(6B)

N(7A)–H(7NA)/S(8B)

N(7B)–H(7NB)/S(8A)

C(21A)–H(2A2)/O(6A)

C(21B)–H(2B1)/O(6B)

C(6A)/C(6A)

C(6A)/O(6A)

C(6B)/C(6B)

C(6B)/O(6B)

F(1A)/C(14A)

x, y, z

2.623(2)

2.590(2)

3.373(2)

3.493(2)

3.052(3)

2.995(3)

3.449(4)

3.443(3)

3.400(4)

3.754(3)

3.140(3)

3.413(3)

3.315(3)

3.136(3)

3.354(3)

2.840(2)

0.91

0.92

0.93

0.96

1.91

1.83

2.45

2.59

2.39

2.43

134

139

160

166

126

117

x, y, z

x, yC1, z

x, yK1, z

x, y, z

KxC1,K yC1,K z

KxC1, KyK1,KzC1

KxC1, Ky, Kz

x, yK1, z

KxC1,K y, KzC1

KxC2, Ky, KzC1

F(1A)/C(13A)

F(3A)/C(5A)

F(1B)/C(14B)

F(1B)/C(13B)

F(1B)/F(2B)

2n

N(9A)–H(9NA)/O(6A)

N(9B)–H(9NB)/O(6B)

N(9C)–H(9NC)/O(6C)

N(9D)–H(9ND)/O(6D)

N(9A)–H(9NA)/O(6C)

N(9B)–H(9NB)/O(6D)

N(9C)–H(9NC)/O(6A)

N(9D)–H(9ND)/O(6B)

N(7A)–H(7NA)/O(1E1)

N(7B)–H(7NB)/O(1E2)

N(7B)–H(7NB)/O(1E”)

C(21A)–H(2A1)/O(6A)

C(21B)–H(2B1)/O(6B)

C(21C)–H(2C1)/O(6C)

C(21D)–H(2D1)/O(6D)

O(6A)/O(6C)

O(6A)/Cl(1C)

S(8A)/O(1E1)

Cl(1A)/N(7C)

Cl(1A)/Cl(1C)

O(1A)/O(6B)

O(1A)/N(7B)

O(1A)/Cl(5A)

O(1A)/Cl(5B)

x, y, z

2.651(3)

2.626(3)

2.636(3)

2.623(4)

3.103(4)

3.088(3)

2.993(3)

3.002(3)

2.888(6)

2.991(8)

3.056(7)

3.056(4)

3.034(4)

3.025(4)

3.028(4)

3.076(3)

3.518(2)

3.315(7)

3.588(3)

3.586(2)

3.292(3)

3.105(3)

3.263(2)

3.421(3)

3. 781(1)

3.145(3)

3.159(7)

3.478(7)

3.745(1)

3.497(2)

3.605(2)

2.974(3)

3.247(3)

0.96

0.99

0.94

0.89

0.96

0.99

0.94

0.89

0.83

0.86

0.96

1.94

1.82

1.98

1.86

2.40

2.38

2.28

2.46

2.11

2.22

2.32

2.39

2.38

2.42

2.40

129

136

125

142

130

128

132

120

157

149

143

126

125

121

122

x, y, z

xK0.5, yK0.5, z

x, KyC1, zC0.5

xK0.5, yK0.5, z

x, yK1, z

x, y, z

S(8A)/Cl(1B)

O(6B)/O(6D)

S(8B)/O(1E”)

S(8B)/O(1E2)

S(8B)/Cl(1A)

O(6B)/Cl(1D)

Cl(1B)/Cl(1D)

O(1B)/O(6A)

x, y, z

xC0.5,KyC1.5, zC0.5

O(1B)/N(7A)

(continued on next page)

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

39

Table 5 (continued)

˚

Distance D–H (A)

˚

Distance H$$A (A)

Atoms involved

Symmetry

Distance D/A (A)

Angle :D–H$$A (8)

O(1B)/Cl(5A)

O(1B)/Cl(5B)

S(8C)/O(1E2)

S(8C)/Cl(1D)

O(1C)/Cl(5C)

N(7D)/Cl(1B)

O(1D)/Cl(5D)

S(8D)/Cl(1C)

xC0.5,KyC1.5, zC0.5

x, KyC2, zC0.5

x, y, z

3.317(3)

3.275(2)

3.653(8)

3.533(1)

3.416(3)

3.579(3)

3.560(3)

3.559(1)

x, y, z

x, KyC2, zK0.5

x, y, z

x, KyC3, zK0.5

x, yC1, z

3e

N(9)–H(9N)/O(6)

C(31)–H(31C)/O(6)

C(15)–H(15)/S(8)

C(14)–H(14)/S(8)

O(1)/O(6)

C(2)/C(2)

C(2)/C(6)

C(2)/O(6)

C(3)/C(6)

C(3)/N(7)

C(4)/O(6)

C(4)/N(9)

C(5)/O(6)

N(7)/C(31)

C(6)/C(13)

C(6)/O(13)

O(6)/C(13)

O(6)/C(14)

N(9)/C(10)

N(9)/C(15)

C(10)/C(10)

O(6)/C(16)

C(5)/O(13)

C(31)/C(31)

x, y, z

2.658(3)

3.083(4)

3.210(3)

3.617(3)

3.321(3)

3.532(5)

3.402(3)

3.534(3)

3.452(3)

3.470(3)

3.592(3)

3.406(4)

3.348(3)

3.584(4)

3.585(4)

3.417(3)

3.554(3)

3.209(4)

3.544(3)

3.560(3)

3.422(5)

3.462(4)

3.503(4)

3.407(6)

0.93

0.96

0.93

0.96

1.89

2.43

2.59

2.80

139

125

124

148

x, y, z

KxC1, Ky, KzC1

KxC2, KyC1, KzC1

KxC1, KyC1, KzC1

KxC1, yC0.5, KzC0.5

xC1, KyC0.5, zC0.5

KxC2, KyC2, KzC1

Esd’s, where given, are in parentheses. The (N–)H atoms were located from difference electron density calculations, and were held riding on their respective

parent N atom during the subsequent reﬁnement calculations, whereas the carbon-bonded H atoms were given calculated positions. The rigid methyl groups,

however, were allowed to rotate around the C/O–C(methyl) bond [48]. The distances/angles have been calculated without correction or normalization of the H

positions.

formed through the carbonyl–carbonyl interactions, are

joined by a pair of (N–)H/S bonds (Table 5), which link

them into endless chains in the crystallographic c-direction

(Fig. 3). The exposed position of the CF₃group in 2e gives

rise to some shorter inter-chain contact distances, involving

the ﬂuoro substituents (Table 5), just as in 1e.

and B–D units in 2n are also hydrogen-bonded to solvate

molecules, thus 2:1 host–guest associates are created via

conventional H-bond interactions (Table 5, Figs. 1(c)

and (d) and 4). Two non-equivalent ethanol molecules (E1

and E2) have been revealed, both being disordered, but in

different ways. Whereas in E1 only the a-carbon was found

to distribute among distinct locations (Fig. 1(c)), the E2

molecule occupies two partly overlapping disorder sites

with only one carbon position in common (Fig. 1(d)).

Because of the inequality of the ethanol molecules, the two

H-bonded host–guest associates, containing E1 and E2,

respectively, also differ somewhat, thus leading to a

asymmetric crystallographic unit of considerable size for

compound 2n, comprising four independent host (A, B, C

and D) and two guest molecules (E1 and E2). Formation of

the hydrogen-bonded host–guest associates gives rise to a

number relatively short host–host and host–guest contact

distances within each 2:1 aggregate. For example, the

N–H/O(ethanol) host–guest hydrogen bonds lead also to

noticeably short S/O(ethanol) distances (Table 5).

In the crystals of the 2n derivative, solvate molecules

were found to be included with 2:1 thiourea–ethanol (i.e.

host–guest) ratio. The host molecules are linked together

two-by-two (i.e. pairs of A–C and B–D molecules; Fig. 1(c)

and (d)) in the very same way as in compound 1e, which in

the case of 2n also leads to relatively short distances

between the two carbonyl oxygens in each closed loop of

˚

(N–)H/O(aC) interactions [3.076(3) A in the A–C, and

˚

3.145(3) A in the B–D pair of molecules; Table 5]. An

important difference is, however, that each dimer in 1e

contains two centrosymmetrically related molecules,

whereas the A, B, C and D molecules in the 2n derivative,

which form the two independent pairs of molecules, are all

crystallographically unique. Moreover, the H-bonded A–C

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

40

Table 6

Moreover, besides shorter intra-aggregate Cl/Cl connec-

tions [with d(Cl/Cl)z3.6 A, Table 5], the chloro sub-

Selected geometric features of compounds 1e, 2e, 2n and 3e

˚

stituents are also involved in relatively short S/Cl

approaches between the H-bonded host–guest associates

Compound

1e

2e

2n

3e

˚

The non-hydrogen atoms are co-planar to within (A)

[S(8C)/Cl(1D)Z3.533(1), S(8D)/Cl(1C)_x,

_zZ

Carbonyl-thiourea

moiety

yC1,

˚

3.559(1) A, Table 5]. Since organic halogens act rather

through speciﬁc anisotropic electronic effects, halogen

contacts with heteroatoms, such as N, O, S or other

halogens, may control crystal packing to varying degrees,

due to their directional character [38]. The Cl/Cl and Cl/

S interactions are assumed to have similar nature and angle

characteristics, although the Cl/S contacts are suggested to

be more energetically signiﬁcant than those between chloro

substituents. The S/Cl approaches in 2n follow the angular

preferences predicted by the electrophile–nucleophile

model of Ramasubbu et al. [39]. Accordingly, the

(Ca)S/Cl–C angle is 160.0(1)8 in both connections (cf.

above), in agreement with the nucleophilic character of the

S/Cl contact. The interactions between sulphur and

chlorine link the H-bonded 2n$EtOH (2:1) associates so

as to form inﬁnite, one-dimensional supramolecules, which

extend parallel with the crystallographic b-direction

(Fig. 4). In addition, there are a few other noteworthy

inter-aggregate connections, involving the furan oxygens

[O(1A) or O(1B)] on the one hand, and various polar atoms/

groups [e.g. (Ca)O, N or Cl-substituents] on the other

(Table 5). These latter observations suggest an electro-

statically favourable packing of the endless supramolecular

chains in 2n.

[O(6)–C(6)–N(7)–

C(8)–S(8)–N(9)]

0.060

0.051

0.019

0.099

0.086

0.155

0.102

0.117

0.069

0.004

0.012

0.003

0.016

0.033

0.018

0.022

0.047

0.007

0.008

Furan ring

0.014

[O(1)–C(2)–C(3)–

C(4)–C(5)]

Phenyl ring

0.010

0.013

[C(10)–C(11)–

C(12)–C(13)–

C(14)–C(15)]

Dihedral angles formed by the LS planes (8)

Carbonyl-thiourea

moiety and the

furan ring

11.1(2)

16.

18.6(2)

5.2(2)

84(11)

11.

11.96(12)

13.0(2)

32(11)

13.2(2)

Carbonyl-thiourea

moiety and the

phenyl ring

76.62(6)

79.46(5)

75.53(6)

87.84(10)

87.63(10)

84.83(9)

84.06(8)

72.70(14)

82.16(13)

72.41(12)

72.17(13)

16.7(2)

19.8(2)

The furan and the

phenyl rings

67.

88.20(8)

72.28(7)

59(13)

Esd’s where given, are in parentheses. The least square (LS) planes were

calculated through the non-hydrogen atoms.

It is apparent from Fig. 5, that the relatively ﬂat 3a

molecules stack upon each other along the crystallographic

a-axis and, by virtue of the inversion symmetry, the

neighbouring molecules within the stack have opposite

Fig. 2. Stereo packing illustration of the crystal structure of the 1e derivative. H atoms are omitted for clarity. Solid and broken lines represent covalent and

hydrogen bonds, respectively.

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

41

Fig. 3. Stereo packing illustration of the 2e derivative. H atoms are omitted for clarity. Broken lines indicate possible hydrogen bonds and the O/C contacts in

the observed carbonyl–carbonyl interactions.

orientations. At the same time, inspection of the inter-

molecular connections reveals several distances between

centrosymmetrically related 3e molecules, which are

considerably shorter than the sum of the van der Waals’

radii of the connected non-hydrogen atoms (Table 5).

Accordingly, the C(6)–O(6)–N(7) and N(9) atoms of the

carbonylthiourea moiety (Fig. 5) form a number of close

contacts with the furan ring atoms that belong to

the molecule related by the KxC2, KyC1, KzC1

symmetry operation. Moreover, atoms of the central

carbonylthiourea skeleton also make noticeably contacts

with the phenyl carbons of the molecule generated by the

KxC1, KyC1, KzC1 symmetry operation. The inter-

planar spacing within the stack is estimated to be between

˚

3.35 and 3.41 A. These observations, together with the fact

that the relatively ﬂat solid-state conformation of the 3a

derivative promotes delocalisation of p-electrons and

formation of extended conjugated p-systems, suggest

Fig. 4. Stereo packing illustration of the 2n$ethanol (2:1) inclusion crystal. The H atoms and the C(1E⁰) ethanol disorder site are omitted for clarity. Broken

˚

lines indicate possible hydrogen bonds and the most probable S/Cl interactions [with d(S/Cl)!3.6 A].

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

42

Fig. 5. Stereo packingdiagram of the 3e derivative. H atoms are omitted for clarity. Possible H-bond interactions are indicated by broken lines between the

connected non-H atoms.

charge-transfer or p/p stacking interaction between

molecules forming the stacks along the a-axis. In the

crystal, these stacks of molecules are then linked through

weak C–H/S hydrogen bonds [19,36] into inﬁnite layers,

which extend perpendicular to the crystallographic c-axis

(Fig. 5).

of CDCl₃or DMSO-d₆solutions were measured with a

1

Varian VXR-300 apparatus (300 MHz for H, 75 MHz for

¹³C) at 25 8C, with tetramethylsilane as internal standard.

3.1. Preparation of methyl-furoyl isothiocyanate

Crystals of the present four compounds were grown

from ethanol solutions under similar experimental con-

ditions. The 1e, 2e and 3e derivatives were found to form

stable crystals on their own. Calculations [40] indicate

close packing and no solvent-accessible space in the

crystals. The crystal packing indices obtained: 68.9% for

both 1e and 2e, and 68.1% for the 3e derivative, are normal

values for close-packed organic crystals [40,41]. Although,

the 2n derivative, containing the 2,6-dichloro-substituted

phenyl ring, was found to form similar hydrogen-bonded

dimeric units as the 1e derivative, the dimeric entities of

2n, unlike those of 1e, turned out to co-crystallize with

ethanol as guest. The included solvent molecules ﬁll up the

voids between the H-bonded host associates, and thus

enhance the packing density and also the stability of the

crystal. Nevertheless, the packing coefﬁcient for 2n

(65.3%) is lower than those previously cited, and the

A solution of 33 g of the corresponding methyl-furoyl

chloride (0.23 mol) in dry acetone (10 cm³) was added

slowly to a vigorously stirred solution of 24 g of dry

potassium thiocyanate (0.24 mol) in dry acetone (260 cm³)

at room temperature during 15 min. The mixture was boiled

for 30 min and then cooled to 0 8C. The precipitate of

potassium chloride was ﬁltered off and the mixture was

evaporated under reduced pressure. The residue was poured

into dry cyclohexane (100 cm³), and the solid was ﬁltered

off. Evaporation of the solvents in vacuo gave a yellow oil,

which was puriﬁed by distillation.

2-Methyl-3-furoyl isothiocyanate: C₇H₅NO₂S yield:

28.8 g (75%); b.p. 60–61 8C/0.05 kPa; IR (CHCl₃):

nZ1697 cm^K1(CO), nZ1965 cm^K1(NCS).

3-Methyl-2-furoyl isothiocyanate: C₇H₅NO₂S yield:

29.2 g (76%); b.p. 86–88 8C/0.16 kPa; IR (CHCl₃):

nZ1699 cm^K1(CO), nZ1972 cm^K1(NCS).

5-Methyl-2-furoyl isothiocyanate: C₇H₅NO₂S yield:

26.9 g (70%); b.p. 60–61 8C/0.26 kPa; IR (CHCl₃):

nZ1692 cm^K1(CO), nZ1978 cm^K1(NCS).

3

˚

calculations indicate also 95 A solvent-accessible free

space in each unit cell of the inclusion crystal. These

observations suggest that the ethanol molecules are not big

enough to ﬁll up the space allotted to the guest molecules

in the crystal, and this in turn makes disorder of the

included alcohol molecules possible.

3.2. Preparation of 1,3-disubstituted thioureas (1a–1n,

2a–2p, 3a–3n, 4a–4f)

A solution of the corresponding amine (0.01 mol) in dry

ether (2 cm³) was added in one portion to a vigorously

stirred solution of the corresponding furoyl isothiocyanate

(0.01 mol) in dry cyclohexane (80 cm³). The mixture was

stirred at 5–10 8C for 5 h. The precipitate was ﬁltered off

and washed with n-hexane (2!10 cm³). By this reaction,

analytically pure compounds were obtained. Thioureas may

be crystallized from a small amount of ethanol.

3. Experimental

Melting points were measured on a Koﬂer micro hot-

stage, and recorded as uncorrected values. Infrared spectra

(wave numbers in cm^K1) were recorded on a PU 9800 FTIR

Philips analytical spectrometer, calibrated with polystyrene

foil, using chloroform as solvent. ¹H and ¹³C NMR spectra

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

43

3.2.1. 1-(2,4-Dimethyl-phenyl)-3-(furan-3-carbonyl)-

thiourea (1c, C₁₄H₁₄N₂O₂S)

3.2.7. 1-(Furan-3-carbonyl)-3-(4-methoxy-phenyl)-thiourea

(1i, C₁₃H₁₂N₂O₃S)

Yield: 82%; m.p.: 172–173 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.25, (s, 3H, CH₃), 2.36 (s, 3H, CH₃), 6.78

(d, d, J_4–5Z1.82 Hz, J_4–2Z0.89 Hz, 1H, 4-H_fur), 7.42 (d, d,

Yield: 69%; m.p.: 135–136 8C; ¹H NMR (DMSO-d₆,

300 MHz): dZ3.72 (s, 3H, OCH₃), 6.94 (d, JZ9.02 Hz, 2H,

H_ar), 7.05 (d, d, J_4–5Z1.86 Hz, J_4–2Z0.94 Hz, 1H, 4-H_fur),

7.52 (d, JZ9.02 Hz, 2H, H_ar), 7.56 (d, d, J_5–4Z1.86 Hz,

J_5–2Z0.84 Hz, 1H, 5-H_fur), 8.72 (br. s, 1H, 2-H_fur), 11.39

(br. s, 1H, NH), 12.45 (br. s, 1H, NH) ppm.

2H, JZ2.16 Hz, JZ8.66 Hz, H_ar), 7.57 (d, d, J_5–4

Z

1.82 Hz, J_5–2Z0.84 Hz, 1H, 5-H_fur), 8.19 (bs, 1H, 2-H_fur),

8.38 (d, 1H, JZ8.66 Hz, H_ar), 8.81 (br. s, 1H, NH), 12.61

(br. s, 1H, NH) ppm.

3.2.8. 1-(Furan-3-carbonyl)-3-(4-triﬂuoromethoxy-phenyl)-

thiourea (1j, C₁₃H₉F₃N₂O₃S)

3.2.2. 1-(4-tert-Butyl-phenyl)-3-(furan-3-carbonyl)-

thiourea (1d, C₁₆H₁₈N₂O₂S)

Yield: 69%; m.p.: 122–123 8C; ¹H NMR (CDCl₃,

300 MHz): dZ6.76 (d, d, J_4–5Z1.79 Hz, J_4–2Z0.85 Hz,

1H, 4-H_fur), 7.25 (d, JZ8.66 Hz, 2H, H_ar), 7.55 (bs, 1H, 5-

Yield: 80%; m.p.: 134–135 8C; ¹H NMR (CDCl₃,

300 MHz): dZ1.32 (s, 9H, CH₃, CH₃, CH₃), 6.75 (d, d,

J_4–5Z1.88 Hz, J_4–2Z0.92 Hz, 1H, 4-H_fur), 7.42 (d, 2H, JZ

8.88 Hz, H_ar), 7.52 (bs, 1H, 5-H_fur), 7.62 (d, 2H, JZ

8.88 Hz, H_ar), 8.14 (d, 1H, J_2–5Z0.92 Hz, 2-H_fur), 8.74 (br.

s, 1H, NH), 12.38 (br. s, 1H, NH) ppm.

H_fur), 7.76 (d, JZ8.66 Hz, 2H, H_ar), 8.15 (br. s, 1H, 2-H_fur),

8.75 (br. s, 1H, NH), 12.76 (br. s, 1H, NH) ppm.

3.2.9. 1-(2-Fluoro-phenyl)-3-(furan-3-carbonyl)-thiourea

(1k, C₁₂H₉FN₂O₂S)

Yield: 81%; m.p.: 153–154 8C; ¹H NMR (CDCl₃,

300 MHz): dZ6.76 (d, d, J_4–5Z1.87 Hz, J_4–2Z0.94 Hz,

1H, 4-H_fur), 7.18–7.34 (d, JZ8.86 Hz, 2H, H_ar), 7.55 (d, 1H,

J_5–4Z1.86 Hz, 5-H_fur), 8.16 (d, d, 1H, J_2–5Z0.94 Hz,

J_2–4Z0.86 Hz, 2-H_fur), 8.16–8.44 (m, 2H, H_ar), 8.78 (br. s,

1H, NH), 12.54 (br. s, 1H, NH) ppm.

3.2.3. 1-(Furan-3-carbonyl)-3-(2-triﬂuoromethyl-phenyl)-

thiourea (1e, C₁₃H₉F₃N₂O₂S)

Yield: 78%; m.p.: 142–143 8C; ¹H NMR (CDCl₃,

300 MHz): dZ6.78 (d, d, J_4–5Z1.87 Hz, J_4–2Z0.84 Hz,

1H, 4-H_fur), 7.42–7.47 (m, 1H, H_ar), 7.53 (d, J_5–4Z1.87 Hz,

1H, 5-H_fur), 7.61–7.72 (t, JZ7.27 Hz, 1H, H_ar), 7.72–7.74

(d, JZ7.74 Hz, 1H, H_ar), 7.92–7.95 (d, JZ7.98 Hz, 1H,

H_ar), 8.18 (d, J_2–4Z1.87 Hz, 1H, 2-H_fur), 8.98 (br. s, 1H,

NH), 12.42 (br. s, 1H, NH) ppm; ¹³C NMR (CDCl₃,

75 MHz): dZ108.2 (C-4_fur), 120.1 (C_ar), 121.9 (C_ar), 125.2

(q, CF₃), 123.2 (C_ar), 127.6 (C_ar), 129.8 (C_ar), 132.2 (C_ar),

135.2 (C_ar), 144.3 (C-5_fur), 147.9 (C-2_fur), 162.2 (CaO),

180.6 (CaS) ppm.

3.2.10. 1-(2,6-Dichloro-phenyl)-3-(furan-3-carbonyl)-

thiourea (1l, C₁₂H₈Cl₂N₂O₂S)

Yield: 89%; m.p.: 192 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ6.77 (d, d, J_4–5Z1.92 Hz, J_4–2Z0.78 Hz, 1H, 4-H_fur),

7.22–7.76 (m, 4H, 5-H_fur, H_ar), 8.18 (d, 1H, J_2–5Z0.98 Hz,

2-H_fur), 8.98 (br. s, 1H, NH), 11.89 (br. s, 1H, NH) ppm.

3.2.11. 1-(Furan-3-carbonyl)-3-(4-iodo-phenyl)-thiourea

(1n, C₁₂H₉IN₂O₂S)

3.2.4. 1-(Furan-3-carbonyl)-3-(3-triﬂuoromethyl-phenyl)-

thiourea (1f, C₁₃H₉F₃N₂O₂S)

Yield: 79%; m.p.: 117–118 8C; ¹H NMR (CDCl₃,

300 MHz): dZ6.77 (d, d, J_4–5Z1.87 Hz, J_4–2Z0.74 Hz,

1H, 4-H_fur), 7.18–8.15 (m, 5H, 5-H_fur, H_ar), 8.19 (bs, 1H,

2-H_fur), 8.84 (br. s, 1H, NH), 12.6 (br. s, 1H, NH) ppm.

Yield: 82%; m.p.: 177–178 8C; ¹H NMR (CDCl₃,

300 MHz): dZ6.75 (bs 1H, 4-H_fur), 7.48 (d, 2H, JZ

8.86 Hz, H_ar), 7.50 (bs, 1H, 5-H_fur), 7.72 (d, 2H, JZ

8.86 Hz, H_ar), 8.15 (d, 1H, J_2–5Z0.82 Hz, 2-H_fur), 8.76 (br.

s, 1H, NH), 12.46 (br. s, 1H, NH) ppm.

3.2.5. 1-(Furan-3-carbonyl)-3-(4-triﬂuoromethyl-phenyl)-

thiourea (1g, C₁₃H₉F₃N₂O₂S)

3.2.12. 1-(2-Methyl-furan-3-carbonyl)-3-phenyl-thiourea

(2a, C₁₃H₁₂N₂O₂S)

Yield: 79%; m.p.: 159–160 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.65 (s, 3H, Fur-CH₃), 6.57 (d, JZ1.96 Hz,

1H, 4-H_fur), 7.34 (d, JZ1.96 Hz, 1H, 5-H_fur), 7.40–7.78 (m,

5H, H_ar), 8.61 (br. s, 1H, NH), 12.49 (br. s, 1H, NH) ppm.

Yield: 72%; m.p.: 151–152 8C; ¹H NMR (CDCl₃,

300 MHz): dZ6.76 (d, d, J_4–5Z1.81 Hz, J_4–2Z0.84 Hz,

1H, 4-H_fur), 7.21–7.36 (m, 2H, H_ar), 7.56 (d, d, J_5–4

Z

1.80 Hz, J_5–2Z0.84 Hz, 1H, 5-H_fur), 8.15 (br. s, 1H, 2-H_fur)

8.75 (br. s, 1H, NH), 12.56 (br. s, 1H, NH) ppm.

,

3.2.13. 1-(2-Methyl-furan-3-carbonyl)-3-(4-methyl-

phenyl)-thiourea (2b, C₁₄H₁₄N₂O₂S)

3.2.6. 1-(3,5-Bis-triﬂuoromethyl-phenyl)-3-(furan-3-

carbonyl)-thiourea (1h, C₁₄H₈F₆N₂O₂S)

Yield: 77%; m.p.: 131–132 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.36 (s, 3H, Ar-CH₃), 2.64 (s, 3H, Fur-

CH₃), 6.56 (d, J_4–5Z1.97 Hz, 1H, 4-H_fur), 7.20 (d, JZ

8.66 Hz, H_ar), 7.33 (d, J_5–4Z1.96 Hz, 1H, 5-H_fur), 7.55 (d,

JZ8.66 Hz, H_ar), 8.62 (br. s, 1H, NH), 12.45 (br. s, 1H,

NH) ppm.

Yield: 69%; m.p.: 112–113 8C; ¹H NMR (CDCl₃,

300 MHz): dZ6.78 (d, d, J_4–5Z1.78 Hz, J_4–2Z0.78 Hz,

1H, 4-H_fur), 7.57 (t, JZ1.78 Hz, 1H, H_ar), 7.76 (bs, 1H,

3- H_fur), 8.21 (t, JZ1.38 Hz, 1H, 2-H_fur), 8.28 (bs, 2H, H_Ar),

8.83 (br. s, 1H, NH), 12.85 (br. s, 1H, NH) ppm.

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44

3.2.14. 1-(2,4-Dimethyl-phenyl)-3-(2-methyl-furan-3-

carbonyl)-thiourea (2c, C₁₅H₁₆N₂O₂S)

JZ8.91 Hz, 2H, H_ar), 8.63 (br. s, 1H, NH), 12.64 (br. s, 1H,

NH) ppm.

Yield: 81%; m.p.: 144–145 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.27 (s, 6H, 2!Ar-CH₃), 2.65 (s, 3H, Fur-

CH₃), 6.57 (d, J_4–5Z2.16 Hz, 1H, 4-H_fur), 7.16 (d, JZ

7.98 Hz, H_ar), 7.37 (d, J_5–4Z2.16 Hz, 1H, 5-H_fur),

7.32–7.49 (m, 2H, H_ar), 8.61 (br. s, 1H, NH), 12.41 (br. s,

1H, NH) ppm.

3.2.20. 1-(2-Methyl-furan-3-carbonyl)-3-(4-

triﬂuoromethoxy-phenyl)-thiourea (2i, C₁₄H₁₁F₃N₂O₃S)

Yield: 76%; m.p.: 145 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.66 (s, 3H, Fur-CH₃), 6.56 (d, J_4–5Z2.17 Hz, 1H,

4-H_fur), 7.24 (d, JZ8.9 Hz, 2H, H_ar), 7.37 (d, J_5–4

Z

2.17 Hz, 1H, 5-H_fur), 7.79 (d, JZ8.9 Hz, 2H, H_ar), 8.64 (br.

s, 1H, NH), 12.62 (br. s, 1H, NH) ppm.

3.2.15. 1-(4-tert-Butyl-phenyl)-3-(2-methyl-furan-3-

carbonyl)-thiourea (2d, C₁₇H₂₀N₂O₂S)

Yield: 76%; m.p.: 139–140 8C; ¹H NMR (CDCl₃,

300 MHz): dZ1.35 (s, 9H, CH₃, CH₃, CH₃), 2.67 (s, 3H,

Fur-CH₃), 6.58 (d, J_4–5Z2.16 Hz, 1H, 4-H_fur), 7.35 (d,

J_5–4Z2.16 Hz, 1H, 5-H_fur), 7.42 (d, JZ8.65 Hz, H_ar), 7.63

(d, JZ8.65 Hz, H_ar), 8.62 (br. s, 1H, NH), 12.51 (br. s, 1H,

NH) ppm; ¹³C NMR (CDCl₃, 75 MHz): dZ14.6 (CH₃),

31.3 (t-But), 108.4 (C-4_fur), 113.8 (C-3_fur), 123.7 (C_ar),

125.7 (C_ar), 135.3 (C_ar), 148.1 (C_ar), 149.8 (C-5_fur), 159.2

(C-2_fur), 163.2 (CZO), 178.8 (CaS) ppm.

3.2.21. 1-(2-Fluoro-phenyl)-3-(2-methyl-furan-3-

carbonyl)-thiourea (2j, C₁₃H₁₁FN₂O₂S)

Yield: 72%; m.p.: 158 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.61 (s, 3H, Fur-CH₃), 6.57 (d, J_4–5Z1.97 Hz, 1H,

4-H_fur), 7.12–7.36 (m, 3H, H_ar), 7.34 (d, J_5–4Z1.97 Hz, 1H,

5-H_fur), 8.24–8.39 (m, 1H, H_ar), 8.67 (br. s, 1H, NH), 12.61

(br. s, 1H, NH) ppm.

3.2.22. 1-(4-Fluoro-phenyl)-3-(2-methyl-furan-3-

carbonyl)-thiourea (2k, C₁₃H₁₁FN₂O₂S)

Yield: 81%; m.p.: 158–159 8C; ¹H NMR (CDCl₃,

3.2.16. 1-(2-Methyl-furan-3-carbonyl)-3-(2-

triﬂuoromethyl-phenyl)-thiourea (2e, C₁₄H₁₁F₃N₂O₂S)

Yield: 79%; m.p.: 144–145 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.61 (s, 3H, Fur-CH₃), 6.57 (d, J_4–5

Z

2.16 Hz, 1H, 4-H_fur), 7.10 (d, JZ4.81 Hz, 1H, H_ar), 7.24 (d,

JZ9.01 Hz, 1H, H_ar), 7.34 (d, J_5–4Z2.16 Hz, 1H, 5-H_fur),

7.52 (d, JZ4.81 Hz, 1H, H_ar), 7.68 (d, JZ9.01 Hz, 1H, H_ar),

8.63 (br. s, 1H, NH), 12.49 (br. s, 1H, NH) ppm.

300 MHz): dZ2.66 (s, 3H, Fur-CH₃), 6.57 (d, J_4–5

Z

1.98 Hz, 1H, 4-H_fur), 7.35 (d, J_5–4Z1.98 Hz, 1H, 5-H_fur),

7.46 (d, JZ8.02 Hz, 2H, H_ar), 7.61–7.79 (m, 2H, H_ar), 7.93

(d, JZ8.02 Hz, 2H, H_ar), 8.74 (br. s, 1H, NH), 12.48 (br. s,

1H, NH) ppm; ¹³C NMR (CDCl₃, 75 MHz): dZ14.6 (CH₃),

106.8 (C-4_fur), 114.9 (C-3_fur), 126.3 (CF₃), 126.9 (C_ar),

130.2 (C_ar), 131.9 (C_ar), 134.7 (C_ar), 137.1 (C_ar), 143.5

(C-5_fur), 157.2 (C-2_fur), 164.9 (CaO), 181.2 (CaS) ppm.

3.2.23. 1-(4-Chloro-phenyl)-3-(2-methyl-furan-3-

carbonyl)-thiourea (2l, C₁₃H₁₁ClN₂O₂S)

Yield: 92%; m.p.: 155 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.64 (s, 3H, Fur-CH₃), 6.56 (d, J_4–5Z2.16 Hz, 1H,

4-H_fur), 7.34 (d, J_5–4Z2.16 Hz, 1H, 5-H_fur), 7.37 (d, JZ

8.86 Hz, 2H, H_ar), 7.66 (d, JZ8.86 Hz, 2H, H_ar), 8.62 (br. s,

1H, NH), 12.59 (br. s, 1H, NH) ppm.

3.2.17. 1-(2-Methyl-furan-3-carbonyl)-3-(3-

triﬂuoromethyl-phenyl)-thiourea (2f, C₁₄H₁₁F₃N₂O₂S)

Yield: 77%; m.p.: 143–144 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.68 (s, 3H, Fur-CH₃), 6.57 (d, J_4–5

Z

3.2.24. 1-(2,3-Dichloro-phenyl)-3-(2-methyl-furan-3-

carbonyl)-thiourea (2m, C₁₃H₁₀Cl₂N₂O₂S)

2.14 Hz, 1H, 4-H_fur), 7.35 (d, J_5–4Z1.98 Hz, 1H, 5-H_fur),

7.49–7.60 (m, 2H, H_ar), 7.92–8.12 (m, 2H, H_ar), 8.64 (br. s,

1H, NH), 12.74 (br. s, 1H, NH) ppm.

Yield: 92%; m.p.: 160–161 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.60 (s, 3H, Fur-CH₃), 6.57 (d, J_4–5

Z

1.98 Hz, 1H, 4-H_fur), 7.36 (d, J_5–4Z1.98 Hz, 1H, 5-H_fur),

7.38 (d, JZ2.36 Hz, 1H, H_ar), 8.26 (d, d, JZ2.36 Hz, JZ

8.2 Hz, 2 H, H_ar), 8.69 (br. s, 1H, NH), 12.73 (br. s, 1H,

NH) ppm.

3.2.18. 1-(2-Methyl-furan-3-carbonyl)-3-(4-

triﬂuoromethyl-phenyl)-thiourea (2g, C₁₄H₁₁F₃N₂O₂S)

Yield: 79%; m.p.: 104 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.66 (s, 3H, Fur-CH₃), 6.56 (d, J_4–5Z2.16 Hz, 1H,

4-H_fur), 7.35 (d, J_5–4Z2.16 Hz, 1H, 5-H_fur), 7.64

(d, JZ8.86 Hz, H_ar), 7.91 (d, JZ8.86 Hz, H_ar), 8.63 (br. s,

1H, NH), 12.81 (br. s, 1H, NH) ppm.

3.2.25. 1-(2,6-Dichloro-phenyl)-3-(2-methyl-furan-3-

carbonyl)-thiourea (2n, C₁₃H₁₀Cl₂N₂O₂S)

Yield: 85%; m.p.: 153–154 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.65 (s, 3H, Fur-CH₃), 6.59 (d, J_4–5

Z

3.2.19. 1-(4-Methoxy-phenyl)-3-(2-methyl-furan-3-

carbonyl)-thiourea (2h, C₁₄H₁₄N₂O₃S)

Yield: 85%; m.p.: 154–155 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.62 (s, 3H, Fur-CH₃), 3.78 (s, 3H, OCH₃),

6.57 (d, J_4–5Z2.17 Hz, 1H, 4-H_fur), 7.24 (d, JZ8.91 Hz,

2H, H_ar), 7.35 (d, J_5–4Z2.17 Hz, 1H, 5-H_fur), 7.78 (d,

1.92 Hz, 1H, 4-H_fur), 7.22–7.48 (m, 4H, 4-H_fur, H_ar), 8.86

(br. s, 1H, NH), 12.01 (br. s, 1H, NH) ppm; ¹³C NMR

(CDCl₃, 75 MHz): dZ14.8 (CH₃), 106.2 (C-4_fur), 114.6 (C-

3_fur), 127.1 (C_ar), 127.2 (C_ar), 129.2 (C_ar), 132.8 (C_ar), 135.6

(C_ar), 136.2 (C_ar), 142.3 (C-5_fur), 159.6 (C-2_fur), 163.8

(CaO), 180.8 (CaS) ppm.

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45

3.2.26. 1-(4-Bromo-phenyl)-3-(2-methyl-furan-3-carbonyl)-

thiourea (2o, C₁₃H₁₁BrN₂O₂S)

2H, H_ar), 7.46 (d, J_5–4Z1.60 Hz, 1H, 5-H_fur), 7.53 (d, JZ

8.55 Hz, 2H, H_ar), 9.18 (br. s, 1H, NH), 12.22 (br. s, 1H,

NH) ppm; ¹³C NMR (CDCl₃, 75 MHz): dZ12.3 (CH₃),

55.3 (OCH₃), 114.2 (C_ar), 116.6 (C-4_fur), 125.6 (C_ar), 130.5

(C-3_fur), 134.2 (C_ar), 139.8 (C-2_fur), 145.0 (C-5_fur), 156.2

(C_ar), 157.8 (CaO), 178.2 (CaS) ppm.

Yield: 89%; m.p.: 150 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.65 (s, 3H, Fur-CH₃), 6.55 (d, J_4–5Z1.97 Hz, 1H,

4-H_fur), 7.35 (d, J_5–4Z1.97 Hz, 1H, 5-H_fur), 7.52 (d, JZ

8.88 Hz, 2H, H_ar), 7.64 (d, JZ8.88 Hz, 2H, H_ar), 8.62 (br. s,

1H, NH), 12.60 (br. s, 1H, NH) ppm.

3.2.33. 1-(3-Methyl-furan-2-carbonyl)-3-(4-

3.2.27. 1-(4-Iodo-phenyl)-3-(2-methyl-furan-3-carbonyl)-

thiourea (2p, C₁₃H₁₁IN₂O₂S)

triﬂuoromethoxy-phenyl)-thiourea (3f, C₁₄H₁₁F₃N₂O₃S)

Yield: 73%; m.p.: 130–131 8C; ¹H NMR (CDCl₃,

300 MHz): d a2.48 (s, 3H, Fur-CH₃), 6.47 (bs, 1H,

4-H_fur), 7.48 (bs, 1H, 5-H_fur), 7.64 (d, JZ8.66 Hz, 2H,

H_ar), 7.93 (d, JZ8.66 Hz, 2H, H_ar), 9.21 (br. s, 1H, NH),

12.64 (br. s, 1H, NH) ppm.

Yield: 93%; m.p.: 165–166 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.67 (s, 3H, Fur-CH₃), 6.55 (d, J_4–5

Z

2.16 Hz, 1H, 4-H_fur), 7.35 (d, J_5–4Z2.17 Hz, 1H, 5-H_fur),

7.48 (d, JZ8.84 Hz, 2H, H_ar), 7.74 (d, JZ8.84 Hz, 2H, H_ar),

8.61 (br. s, 1H, NH), 12.61 (br. s, 1H, NH) ppm.

3.2.34. 1-(2-Fluoro-phenyl)-3-(3-methyl-2-furan-

carbonyl)-thiourea (3g, C₁₃H₁₁FN₂O₂S)

Yield: 82%; m.p.: 150 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.46 (s, 3H, Fur-CH₃), 6.46 (bs, 1H, 4-H_fur), 7.06 (m,

3H, H_ar),7.47 (bs, 1H, 5-H_fur), 8.21–8.52 (m, 1H, H_ar), 9.23

(br. s, 1H, NH), 12.48 (br. s, 1H, NH) ppm.

3.2.28. 1-(3-Methyl-furan-2-carbonyl)-3-(4-methyl-

phenyl)-thiourea (3a, C₁₄H₁₄N₂O₂S)

Yield: 88%; m.p.: 130–131 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.34 (s, 3H, Ar-CH₃), 2.44 (s, 3H, Fur-

CH₃), 6.46 (d, J_4–5Z1.59 Hz, 1H, 4-H_fur), 7.20 (d, JZ

8.36 Hz, 2H, H_ar), 7.48 (d, J_5–4Z1.59 Hz, 1H, 5-H_fur), 7.55

(d, JZ8.36 Hz, 2H, H_ar), 9.24 (br. s, 1H, NH), 12.28 (br. s,

1H, NH) ppm.

3.2.35. 1-(4-Fluoro-phenyl)-3-(3-methyl-2-furan-

carbonyl)-thiourea (3h, C₁₃H₁₁FN₂O₂S)

Yield: 78%; m.p.: 133–134 8C; ¹H NMR (CDCl₃,

3.2.29. 1-(3-Methyl-furan-2-carbonyl)-3-(2,4-dimethyl-

phenyl)-thiourea (3b, C₁₅H₁₆N₂O₂S)

300 MHz): dZ2.44 (s, 3H, Fur-CH₃), 6.47 (d, J_4–5

Z

1.61 Hz, 1H, 4-H_fur), 7.05 (d, JZ8.84 Hz, 1H, H_ar), 7.23 (d,

JZ4.9 Hz, 1H, H_ar), 7.49 (d, J_5–4Z1.61 Hz, 1H, 5-H_fur),

7.62 (d, JZ8.84 Hz, 2H, H_ar), 7.69 (d, JZ4.92 Hz, 2H, H_ar),

9.21 (br. s, 1H, NH), 12.32 (br. s, 1H, NH) ppm; ¹³C NMR

(CDCl₃, 75 MHz): dZ11.4 (CH₃), 115.6 (d, JZ22.3 Hz,

C_ar), 116.5 (C-4_fur), 126.1 (d, JZ8.3 Hz, C_ar), 130.5

(C-3_fur), 133.7 (C_ar), 139.8 (C-2_fur), 146.1 (C-5_fur), 161.2

(d, JZ254.2 Hz, C_ar), 155.6 (CaO), 178.7 (CaS) ppm.

Yield: 86%; m.p.: 136–137 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.26 (s, 6H, 2!Ar-CH₃), 2.44 (s, 3H, Fur-

CH₃), 6.45 (d, J_4–5Z1.58 Hz, 1H, 4-H_fur), 7.16 (d, JZ

8.46 Hz, 2H, H_ar), 7.42 (d, JZ8.46 Hz, 2H, H_ar), 7.45 (d,

J_5–4Z1.59 Hz, 1H, 5-H_fur), 9.15 (br. s, 1H, NH), 12.24 (br.

s, 1H, NH) ppm.

3.2.30. 1-(4-tert-Butyl-phenyl)-3-(3-methyl-2-furan-

carbonyl)-thiourea (3c, C₁₇H₂₀N₂O₂S)

Yield: 75%; m.p.: 118–119 8C; ¹H NMR (CDCl₃,

300 MHz): dZ1.33 (s, 9H, 3!CH₃), 2.46 (s, 3H, Fur-

CH₃), 6.46 (d, J_4–5Z1.59 Hz, 1H, 4-H_fur), 7.42 (d, JZ

3.2.36. 1-(2,4-Diﬂuoro-phenyl)-3-(3-methyl-2-furan-

carbonyl)-thiourea (3i, C₁₃H₁₀F₂N₂O₂S)

Yield: 80%; m.p.: 174–175 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.48 (s, 3H, Fur-CH₃), 6.47 (d, J_4–5

1.59 Hz, 1H, 4-H_fur), 6.63–7.32 (m, 2H, H_ar), 7.47 (d, J_5–4

Z

8.75 Hz, H_ar), 7.53 (d, JZ8.75 Hz, H_ar), 7.55 (d, J_5–4

Z

1.59 Hz, 1H, 5-H_fur), 9.26 (br. s, 1H, NH), 12.48 (br. s, 1H,

NH) ppm.

1.59 Hz, 1H, 5-H_fur), 8.2–8.43 (m, 1H, H_ar), 9.24 (br. s, 1H,

NH), 12.26 (br. s, 1H, NH) ppm.

3.2.31. 1-(3-Methyl-furan-2-carbonyl)-3-(4-

triﬂuoromethyl-phenyl)-thiourea (3d, C₁₄H₁₁F₃N₂O₂S)

Yield: 79%; m.p.: 127–128 8C; ¹H NMR (CDCl₃,

3.2.37. 1-(4-Chloro-phenyl)-3-(3-methyl-2-furan-

carbonyl)-thiourea (3j, C₁₃H₁₁ClN₂O₂S)

Yield: 81%; m.p.: 153 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.44 (s, 3H, Fur-CH₃), 6.47 (d, J_4–5Z1.38 Hz, 1H,

300 MHz): dZ2.46 (s, 3H, Fur-CH₃), 6.48 (d, J_4–5

Z

1.58 Hz, 1H, 4-H_fur), 7.49 (d, J_5–4Z1.58 Hz, 1H, 5-H_fur),

7.49 (d, JZ8.92 Hz, 2H, H_ar), 7.91 (d, JZ8.92 Hz, 2H, H_ar),

9.23 (br. s, 1H, NH), 12.60 (br. s, 1H, NH) ppm.

4-H_fur), 7.36 (d, JZ8.85 Hz, 2H, H_ar), 7.47 (d, J_5–4

1.38 Hz, 1H, 5-H_fur), 7.73 (d, JZ8.85 Hz, 2H, H_ar), 9.19 (br.

s, 1H, NH), 12.43 (br. s, 1H, NH) ppm.

Z

3.2.32. 1-(4-Methoxy-phenyl)-3-(3-methyl-2-furan-

carbonyl)-thiourea (3e, C₁₄H₁₄N₂O₃S)

Yield: 83%; m.p.: 124–125 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.44 (s, 3H, Fur-CH₃), 3.82 (s, 3H, OCH₃),

6.46 (d, J_4–5Z1.60 Hz, 1H, 4-H_fur), 6.93 (d, JZ8.61 Hz,

3.2.38. 1-(2,6-Dichloro-phenyl)-3-(3-methyl-2-furan-

carbonyl)-thiourea (3k, C₁₃H₁₀Cl₂N₂O₂S)

Yield: 72%; m.p.: 194 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.46 (s, 3H, Fur-CH₃), 6.47 (bs, 1H, 4-H_fur), 7.21–7.56

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O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

46

(m, 4H, 5-H_fur, H_Ar), 9.37 (br. s, 1H, NH), 11.92 (br. s, 1H,

NH) ppm.

125.1 (C_Ar), 127.4 (d, JZ8.3 Hz, C_ar), 144.3 (d, JZ

251.6 Hz, C_ar), 153.2 (C-2_fur), 156.7 (CaO), 157.9 (C-5_fur),

178.3 (CaS) ppm.

3.2.39. 1-(3,4-Dichloro-phenyl)-3-(3-methyl-2-furan-

carbonyl)-thiourea (3l, C₁₃H₁₀Cl₂N₂O₂S)

Yield: 75%; m.p.: 150 8C; ¹H NMR (CDCl₃, 300 MHz):

dZ2.44 (s, 3H, Fur-CH₃), 6.48 (d, J_4–5Z1.52 Hz, 1H,

4-H_fur), 7.24–7.68 (m, 3H, 5-H_fur, H_ar), 7.95 (d, JZ2.16 Hz,

1H, H_Ar), 9.21 (br. s, 1H, NH), 12.51 (br. s, 1H, NH) ppm.

3.2.45. 1-(4-Fluoro-phenyl)-3-(5-methyl-2-furan-

carbonyl)-thiourea (4d, C₁₃H₁₁FN₂O₂S)

Yield: 78%; m.p.: 148–149 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.43 (s, 3H, Fur-CH₃), 6.24 (d, d, J_4–3

Z

3.38 Hz, JZ0.98 Hz, 1 H, 4-H_fur), 7.28 (d, J_3–4Z3.38 Hz,

1H, 3-H_fur), 7.62 (dd, JZ8.86 Hz, JZ4.32 Hz, 2H, H_ar),

9.14 (br. s, 1H, NH), 12.31 (br. s, 1H, NH) ppm.

3.2.40. 1-(4-Bromo-phenyl)-3-(3-methyl-2-furan-carbonyl)-

thiourea (3m, C₁₃H₁₁BrN₂O₂S)

Yield: 78%; m.p.: 154–155 8C; ¹H NMR (CDCl₃,

3.2.46. 1-(2,4-Diﬂuoro-phenyl)-3-(5-methyl-2-furan-

carbonyl)-thiourea (4e, C₁₃H₁₀F₂N₂O₂S)

300 MHz): dZ2.44 (s, 3H, Fur-CH₃), 6.46 (d, J_4–5

Z

1.57 Hz, 1H, 4-H_fur), 7.47 (d, J_5–4Z1.57 Hz, 1H, 5-H_fur),

7.49 (d, JZ8.66 Hz, 2H, H_ar), 7.66 (d, JZ8.66 Hz, 2H, H_ar),

9.19 (br. s, 1H, NH), 12.43 (br. s, 1H, NH) ppm.

Yield: 82%; m.p.: 175–176 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.43 (s, 3H, Fur-CH₃), 6.24 (d, d, J_4–3

Z

3.45 Hz, JZ0.78 Hz, 1 H, 4-H_fur), 6.81–7.16 (m, 1H, H_ar),

7.32 (d, J_3–4Z3.38 Hz, 1H, 3-H_fur), 8.03–8.41 (m, 2H, H_ar),

9.22 (br. s, 1H, NH), 12.33 (br. s, 1H, NH) ppm.

3.2.41. 1-(4-Iodo-phenyl)-3-(3-methyl-2-furan-carbonyl)-

thiourea (3n, C₁₃H₁₁IN₂O₂S)

Yield: 82%; m.p.: 176–177 8C; ¹H NMR (CDCl₃,

3.2.47. 1-(2,4-Dichloro-phenyl)-3-(5-methyl-2-furan-

carbonyl)-thiourea (4f, C₁₃H₁₀Cl₂N₂O₂S)

300 MHz): dZ2.41 (s, 3H, Fur-CH₃), 6.44 (d, J_4–5

Z

1.52 Hz, 1H, 4-H_fur), 7.44 (d, J_5–4Z1.52 Hz, 1H, 5-H_fur),

7.47 (d, JZ8.12 Hz, 2H, H_ar), 7.68 (d, JZ8.12 Hz, 2H, H_ar),

9.15 (br. s, 1H, NH), 12.41 (br. s, 1H, NH) ppm; ¹³C NMR

(CDCl₃, 75 MHz): dZ12.3 (CH₃), 91.1 (C_Ar), 116.7 (C-

4_fur), 125.8 (C_ar), 133.9 (C_Ar), 137.5 (C-3_fur), 138.3 (C_Ar),

139.8 (C-2_fur), 144.6 (C-5_fur), 155.6 (CaO), 178.7 (CaS)

ppm.

Yield: 81%; m.p.: 202–203 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.41 (s, 3H, Fur-CH₃), 6.26 (d, d, J_4–3

Z

3.45 Hz, JZ0.78 Hz, 1 H, 4-H_fur), 7.31 (d, J_3–4Z3.54 Hz,

1H, 3-H_fur), 7.44–7.58 (m, 2H, H_ar), 7.98 (d, JZ1.96 Hz,

1H, H_ar), 9.15 (br. s, 1H, NH), 12.47 (br. s, 1H, NH) ppm.

The preparation and some properties of the studied

compounds 1a, 1b, 1m have been described in the literature

[42].

3.2.42. 1-(4-tert-Butyl-phenyl)-3-(5-methyl-2-furan-

carbonyl)-thiourea (4a, C₁₇H₂₀N₂O₂S)

3.3. Spectroscopic methods

Yield: 89%; m.p.: 156–158 8C; ¹H NMR (CDCl₃,

300 MHz): dZ1.38 (s, 9H, CH₃, CH₃, CH₃), 2.41 (s, 3H,

Fur-CH₃), 6.23 (d, d, J_4–3Z3.41 Hz, JZ0.78 Hz, 1 H,

4-H_fur), 7.28 (d, J_3–4Z3.41 Hz, 1H, 3-H_fur), 7.42 (d, JZ

8.72 Hz, 2H, H_ar), 7.63 (d, JZ8.72 Hz, 2H, H_ar), 9.13 (br. s,

1H, NH), 12.32 (br. s, 1H, NH) ppm.

The IR spectra for hydrogen bond study were measured

at room temperature in the region 4000–600 cm^K1, using a

Zeiss Specord M 85 spectrometer. The measurements were

carried out in CHCl₃(Uvasol) employing NaCl cells of

0.05 cm thickness. The concentrations of the solutions were

5!10^K2mol dm^K3. The absorption intensities of the Fermi

triplet components were determined after mathematical

deconvolution and separation of overlapping bands. Curve

analysis was carried out with a digital curve-ﬁtting routine.

3.2.43. 1-(5-Methyl-2-furan-carbonyl)-3-(3-

triﬂuoromethyl-phenyl)-thiourea (4b, C₁₄H₁₁F₃N₂O₂S)

Yield: 80%; m.p.: 156–158 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.44 (s, 3H, Fur-CH₃), 6.25 (d, d, J_4–3

Z

3.54 Hz, JZ0.98 Hz, 1 H, 4-H_fur), 7.29 (d, J_3–4Z3.54 Hz,

1H, 3-H_fur), 7.52 (d, JZ5.35 Hz, 2H, H_ar), 7.85–8.16 (m,

2H, H_ar), 9.17 (br. s, 1H, NH), 12.56 (br. s, 1H, NH) ppm.

3.4. Semi-empirical calculations

All semi-empirical calculations were performed by

means of AM1 [43] and PM3 [44], using the program

package MOPAC 6.0 [45]. The calculations were carried

out as simulations at a temperature of 298 K and a pressure

of 1 atm.

3.2.44. 1-(2-Fluoro-phenyl)-3-(5-methyl-2-furan-

carbonyl)-thiourea (4c, C₁₃H₁₁FN₂O₂S)

Yield: 76%; m.p.: 128–129 8C; ¹H NMR (CDCl₃,

300 MHz): dZ2.43 (s, 3H, Fur-CH₃), 6.24 (d, d, J_4–3

Z

3.42 Hz, JZ0.73 Hz, 1 H, 4-H_fur), 7.10–7.28 (m, 3H, H_Ar),

7.29 (d, J_3–4Z3.42 Hz, 1H, 3-H_fur), 8.32–8.47 (m, 1H, H_ar),

9.52 (br. s, 1H, NH), 12.79 (br. s, 1H, NH) ppm; ¹³C NMR

(CDCl₃, 75 MHz): dZ13.7 (CH₃), 109.9 (C-4_fur), 115.3 (d,

JZ21.6 Hz, C_ar), 118.9 (C_Ar), 120.6 (C-3_fur), 123.7 (C_Ar),

3.5. Crystallography

Single crystals, suitable for X-ray diffraction analysis,

were grown from ethanol solutions. Intensity data were

collected at room temperature (293G2 K), using a STOE

´

O. Hritzova et al. / Journal of Molecular Structure 743 (2005) 29–48

47

IPDS (Imaging Plate Detection System) instrument,

equipped with a rotating anode and Mo K_aradiation (lZ

disordered E2 molecule. As a consequence, some rest

electron density was observed in the ﬁnal difference electron

K

3

˚

0.71073 A). Data reduction calculations [46] included

˚

density map (Dr_maxZ0.58 e /A ), located in the vicinity of

the ethanol molecules, and indicating the approximate

character of the disorder models. Although neither the 2n

derivative nor the guest ethanol contain a molecular

stereogenic centre, the realized packing arrangement lacks

inversion symmetry (i.e. is non-centrosymmetric). In the

last stage of the structure reﬁnement the calculated absolute

structure or Flack parameter [48] reached a value of 0.02(4),

thus indicating that the handedness of the 2n crystal is most

likely that shown in Fig. 4.

corrections for Lorentz and polarization effects, but not

for absorption or extinction effects. In the reﬁnement of the

unit cell parameters, the most suitable 5000 reﬂections were

selected and used [46].

Application of direct methods [47] yielded preliminary

structure models, which were completed and reﬁned using

the ^SHELXL-97 programs [48]. The non-hydrogen atoms and

disorder sites (e.g. in 2n) were reﬁned together with their

anisotropic displacement parameters, whereas the hydrogen

atom positions were treated isotropically. The (N–)H atoms

and possible (O–)H disorder sites were located from

difference electron density maps, and were held riding on

their parent N/O atoms in the subsequent calculations,

whereas the carbon-bonded hydrogens were given positions

deduced from geometric evidence. The rigid methyl groups,

on the other hand, were allowed to rotate around the

respective C/O–C(methyl) bonds [48].

Crystal data, together with details of the data reduction

and structure reﬁnement calculations are shown in Table 4.

Crystallographic data (including ﬁnal atomic coordinates

and geometric parameters, and excluding structure factors)

for the structure analyses have been deposited with the

Cambridge Crystallographic Data Centre, CCDC No.

240290 for 1e, 240291 for 2e, 240292 for 2n and 240293

for 3e. Copies of the data can be obtained free of charge on

application to CCDC, 12 Union Road, Cambridge CB2 1EZ,

UK (fax: int. Code C44 1223 336 033; e-mail: deposit@

ccdc.cam.ac.uk).

Although a preliminary structure model of the 2e

compound could easily be deduced from the collected

X-ray data, all efforts to properly reﬁne the structure failed.

Careful inspection of the intensity data proved the crystals

of 2e to be twins (non-merohedral twins). The reﬂections,

coming from the two crystal domains, could be resolved

using programs available in the software supplied with the

STOE IPDS diffractometer [46]. New data reduction

calculations were carried out, one for each intensity data

set. Then, the two sets of structure factors (F²values), one

from each domain, were used in the reﬁnement calculations,

after appropriate scaling and merging [48–50].

Acknowledgements

This work was supported by the Grant Agency VEGA

(Grant No. 1/0071/03). I.C. is indebted to Lars Eriksson

(Stockholm University) for his help in the resolution of

the reﬂection intensities collected from the 2e twin

crystal.

The triclinic (P-1) crystals of 2e contain two symmetry-

independent molecules (A and B) (Fig. 1(b)). The related 2n

compound, on the other hand, crystallizes with monoclinic

(Cc) space group symmetry, and with four unique 2n

molecules (A, B, C and D) and two ethanol solvates (E1 and

E2) in each asymmetric crystallographic unit (Fig. 1(c) and

(d)). Both solvate molecules exhibit disorder, static as well

as dynamic (indicated by partial site occupancy, and

relatively high atomic displacement parameters, respect-

ively), but in different ways. Two disorder sites could be

realized for the a-carbon of E1, C(1E1) and C(1E⁰), with

the site occupation factors 0.64 and 0.36, respectively

[assuming full occupancy (Z1.0) for the pair of corre-

sponding un-primed/primed disorder sites together],

whereas the E2 molecule occupies at least two, partly

overlapping disorder sites, having only the C(2E2) position

in common. The probabilities of the un-primed and double-

primed sites in E2 reﬁned to 47 and 53%, respectively. The

partially occupied ethanol O and C positions had to be

reﬁned with simple distance constraints in order to yield

acceptable geometry for the guest alcohol skeletons.

Moreover, because of the high mobility of the solvate

entities, the ﬁnal structure model comprises neither minor H

disorder sites for E1, nor H sites at all for the heavily

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Article Doi

Furan derivatives of substituted phenylthiourea: Spectral studies, semi-empirical quantum-chemical calculations and X-ray structure analyses

DOI: 10.1016/j.molstruc.2005.02.014

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