Synthesis and structural characterization of fluorinated thiosemicarbazones

Article abstract of DOI:10.3390/molecules181013111

Six new fluorinated thiosemicarbazones R-C(R′)=N-NH-C(S)NH ₂ (R = 2,4-C₆H₃F₂, R′ = H (1); R = 2,5-C₆H₃F₂, R′ = H (2); R = 2,6-C₆H₃F₂, R′ = H (3);

Full text of DOI:10.3390/molecules181013111

Molecules 2013, 18, 13111-13123; doi:10.3390/molecules181013111
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis and Structural Characterization of
Fluorinated Thiosemicarbazones
Juan L. Bautista 1, Marcos Flores-Alamo 2, Jorge Tiburcio 3, Rebeca Vieto 2 and Hugo Torrens 2,*
1
Facultad de Ciencias Químicas, Universidad Autónoma Benito Juárez de Oaxaca. Av. Universidad S/N
Cinco Señores, Oaxaca de Juárez, Oaxaca 68000, Mexico; E-Mail: jlbautista@hotmail.com
2
Facultad de Química, UNAM, Cd. Universitaria, 04510 México D.F., Mexico;
E-Mails: mfa@unam.mx (M.F.A.); rebecaq@gmail.com (R.V.)
3
Departamento de Química, CINVESTAV, Av. Instituto Politécnico Nacional No. 2508,
San Pedro Zacatenco, México 07360, Mexico; E-Mail: jtiburcio@cinvestav.mx
* Author to whom correspondence should be addressed; E-Mail: torrens@unam.mx;
Tel./Fax: +52-555-622-3724.
Received: 10 September 2013; in revised form: 10 October 2013 / Accepted: 11 October 2013 /
Published: 22 October 2013
Abstract: Six new fluorinated thiosemicarbazones R-C(R′)=N-NH-C(S)NH2 (R = 2,4-C6H3F2,
R′ = H (1); R = 2,5-C6H3F2, R′ = H (2); R = 2,6-C6H3F2, R′ = H (3); R = 3,4-C6H3F2,
R′ = H (4); R = 3,5-C6H3F2, R′ = H (5) and R = 4-C6H4F, R′ = C6H5, (6)) have been
prepared. The molecular structures of compounds 1 to 6 have been determined.
Key words: fluorobenzaldehyde; sulfur; thiosemicarbazones; crystal structure
1. Introduction
Studies focusing on thiosemicarbazones date back to the beginning of the last century, but the first
reports on their pharmaceutical applications as drugs against leprosy and tuberculosis were published
in the 1950s [1,2]. Later, their antiviral and antitumoral [3] properties, as well as their involvement in
the treatment of smallpox [4] triggered a huge amount of research.
Today, thiosemicarbazones are the focus of a growing interest because many of their properties are
relevant to a wide range of fields. These compounds, formed by the condensation of thiosemicarbazide
and aldehyde or ketone have endless combinations and the presence of at least amide, imine and thione
groups, makes them a class of potent potential polydentate ligands that have proven to be very efficient

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metal chelators and it is not surprising that numerous thiosemicarbazone complexes have been
prepared and characterized [5].
Studies of thiosemicarbazone derivatives include investigations of corrosion inhibitors for
metal alloys [6], metal extraction and separation [7] applications in spectrophotometry, fluorometry,
atomic absorption spectrophotometry and as chemical sensors [8], supramolecular chemistry [9],
optoelectronics [10] and pharmacological activity [11] as antitumoral, fungicidal, bactericidal and
antiviral drugs.
We have been interested in fluorinated compounds for a long time [12] since inclusion of fluorine
atoms in molecules often has a marked effect on their physical and chemical properties. For example,
although it has been recognized that fluorine-containing drugs are often far more therapeutically active
than their non-fluorinated analogs [13] it is surprising that relatively very little is known about the
properties of fluorine-containing thiosemicarbazones [14,15]. In this paper, we report the syntheses of
six new polyfluorobenzaldehyde thiosemicarbazones: RC(R′)=N-NH-C(S)NH2 (R = 2,4-C6H3F2,
R′ = H (1); R = 2,5-C6H3F2, R′ = H (2); R = 2,6-C6H3F2, R′ = H (3); R = 3,4-C6H3F2, R′ = H (4);
R = 3,5-C6H3F2, R′ = H (5) and R = 4-C6H4F, R′ = C6H5, (6)) and their corresponding X-ray
diffraction structures.
2. Results and Discussion
The corresponding aldehydes RCHO (R = 2,4-C6H3F2, (1); R = 2,5-C6H3F2, (2); R = 2,6-C6H3F2, (3);
R = 3,4-C6H3F2, (4); R = 3,5-C6H3F2, (5) or ketone ((4-C6H4F)C(=O)(C6H5) (6)) was dissolved in
ethanol at room temperature and added to solutions of thiosemicarbazide in a 1:1 mixture of
ethanol/water, along with catalytic amounts of acetic acid (Scheme 1). The reaction mixtures were
refluxed for 24 h and then the solvent was reduced under vacuum to one third of the original volume,
from which the products precipitated as white crystalline solids. Compounds 1–6 were recrystallized
from ethanol/water (1:1) and characterized by 1H-, 13C- and 19F{1H}-NMR, MS and IR.
Scheme 1. Preparation of the polyfluoroaryl thiosemicarbazones 1 to 6.
The X-ray diffraction molecular and crystal structures of compounds 1 to 6 have been determined [16].
The molecular structures and atom numbering schemes of compounds 1 to 6 are shown on Figure 1 to
Figure 6 along with selected bond distances and angles.

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Figure 1. ORTEP drawing of 2,4-C6H3F2-CH=N-NH-C(S)NH2 (1). Thermal ellipsoids are
shown at 50% of probability. Selected bond lengths (Å) and angles (°): S1-C1 1.690(16),
C1-N1 1.315(2), C1-N2 1.3400(19), N2-N3 1.3692(17), N3-C2 1.2728(19) C2-C3
1.462(2) C4-F1 1.3565(18), C6-F2 1.361(2); S1-C1-N1 122.99(13), S1-C1-N2 119.97(11),
N1-C1-N2 117.04(15), N2-N3-C2, N3-C2-C3 117.26(13).
Figure 2. ORTEP drawing of 2,5-C6H3F2-CH=N-NH-C(S)NH2 (2). Thermal ellipsoids are
shown at 50% of probability. Selected bond lengths (Å) and angles (°): S1-C1 1.6881(15),
C1-N1 1.3182(19), C1-N2 1.3438(18), N2-N3 1.3752(17), N3-C2 1.2699(19) C2-C3
1.462(2) C4-F1 1.355(2), C7-F2 1.356(2); S1-C1-N1 123.45(12), S1-C1-N2 119.04(11),
N1-C1-N2 117.51(14), N2-N3-C2 115.50(13), N3-C2-C3 120.02(15).

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Figure 3. ORTEP drawing of 2,6-C6H3F2-CH=N-NH-C(S)NH2 (3, molecule A). Thermal
ellipsoids are shown at 50% of probability. Selected bond lengths (Å) and angles (°): S1A-C1A
1.6926(18), C1A-N1A 1.320(2), C1A-N2A 1.339(2) N2A-N3A 1.378(2), N3A-C2A
1.276(2), C2A-C3A 1.458(3), C4A-F1A 1.348(2), C8A-F2A 1.341(2); S1A-C1A-N1A
123.39(14), S1A-C1A-N2A 118.68(14), N1A-C1A-N2A 117.92(17), N2A-N3A-C2A
114.48(15), N3A-C2A-C3A 122.99(17).
Figure 4. ORTEP drawing of 3,4-C6H3F2-CH=N-NH-C(S)NH2 (4). Thermal ellipsoids are
shown at 50% of probability. Selected bond lengths (Å) and angles (°): S1-C1 1.6788(14),
C1-N1 1.3261(18), C1-N2 1.3407(17), N2-N31.3773(15),N3-C2 1.2743(17), C2-C3
1.4612(18), C5-F1 1.3478(18), C6-F2 1.3511(16); S1-C1-N1 122.76(11), S1-C1-N2
120.24(10), N1-C1-N2 116.99(13), N2-N3-C2 115.55(11), N3-C2-C3 120.89(13).

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Figure 5. ORTEP drawing of 3,5-C6H3F2-CH=N-NH-C(S)NH2 (5). Thermal ellipsoids are
shown at 50% of probability. Selected bond lengths (Å) and angles (°): S1-C1 1.6890(14),
C1-N1 1.3164(19), C1-N2 1.3439(19), N2-N3 1.3699(16), N3-C2 1.2769(19), C2-C3
1.464(2), C5-F1 1.357(2), C7-F2 1.357(2); S1-C1-N1 123.19(12), S1-C1-N2 119.64(11),
N1-C1-N2 117.17(13), N2-N3-C2 116.29(12), N3-C2-C3 119.68(14).
Figure 6. ORTEP drawing of 4-C6H4F-C(C6H5)=N-NH-C(S)NH2 (6). Thermal ellipsoids
are shown at 50% of probability. Selected bond lengths (Å) and angles (°): S1-C1 1.686(5),
C1-N1 1.316(5), C1-N2 1.347(6), N2-N3 1.374(5), N3-C2 1.278(6), C2-C3 1.495(5),
C2-C9 1.488(6), C6-F1 1.346(6); S1-C1-N1 123.8(3), S1-C1-N2 119.3(3), N1-C1-N2
116.9(4), N2-N3-C2 118.1(3), N3-C2-C3 123.8(4), N3-C2-C9 116.5(4).
The IR spectra of compounds 1 to 6 show the expected signals from the polyfluoroaldehydes and
the thiosemicarbazone groups, respectively [17]. The 1H-NMR spectra of compounds 1 to 6 exhibit the
expected aromatic signals at ca. 8–11 ppm. In the thiosemicarbazones’ spectra there is a broad singlet
at low field attributed to the NH- group and two broad singlets between 7 and 8 ppm assigned to each

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hydrogen atom in the -NH2 group, which show different magnetic behavior due to the double bond
character in the C-N bond restricting its free rotation. Compounds 1–5 show a singlet at ca. 8 ppm due
to the CH = N group [18].
In the solid state the thiosemicarbazone moieties in compounds 1–6 show an E configuration with
the sulfur atom trans to the iminic nitrogen N3. All synthesized thiosemicarbazones exhibit the thione
tautomeric form both in solution and in the solid state. This form is favored by the formation of the
intramolecular N(1)-H---N(3) hydrogen bridge. Intramolecular and intermolecular hydrogen bonding
occurs in all six molecules [19].
The crystalline structures seem to be stabilized by the effect of N-H---S hydrogen bridges. As
expected the relative position of the fluorine substituents on the aromatic ring of compounds 1 to 6 has
a noticeable influence, not only on the chemical behavior of these compounds, but also on the different
crystal packing arrangements, as shown in Figure 7 to Figure 12. The C2-N3 bond distances exhibit
the expected values for a double bond. C1-S1 bond distances (average: 1.68 Å) are in between those of
a C-S single bond (1.82 Å) and a C=S double bond (1.56 Å) thus reflecting a partial double bond
character [20]. Both C1-N1 and C1-N2 bond lengths are shorter than the distance expected for a single
C-N bond. N2-N3 bond length is also shorter than expected for a single N-N bond and therefore a
delocalization seems to be present on this fragment.
Figure 7. Packing arrangement of 2,4-C6H3F2-CH=N-NH-C(S)NH2 (1) showing the π
interactions between thiophenolate rings.
Figure 8. Packing arrangement of 2,5-C6H3F2-CH=N-NH-C(S)NH2 (2) showing the π
interactions between thiophenolate rings.

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Figure 9. Packing arrangement of 2,6-C6H3F2-CH=N-NH-C(S)NH2 (3) showing the π
interactions between thiophenolate rings.
Figure 10. Packing arrangement of 3,4-C6H3F2-CH=N-NH-C(S)NH2 (4) showing the π
interactions between thiophenolate rings.
Figure 11. Packing arrangement of 3,5-C6H3F2-CH=N-NH-C(S)NH2 (5) showing the π
interactions between thiophenolate rings.

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Figure 12. Packing arrangement of 4-C6H4F-C(C6H5)=N-NH-C(S)NH2 (6) showing the π
interactions between thiophenolate rings.
Two types of intermolecular interactions are observed in the supramolecular structures of
compounds 1 to 6, there are π interactions between aromatic rings from neighbor molecules and also,
there are intermolecular hydrogen-bond interactions with a 2.39 Å minimum distance and 2.89 Å as a
maximum distance interaction.
3. Experimental
3.1. General
All reactions were carried out under dry, oxygen-free N2 atmospheres, using Schlenk techniques.
Solvents were dried and degassed prior to use, using standard techniques [21]. Microanalyses were
performed using a Fisons EA1108 instrument. FT-IR spectra were recorded over the 4000–200 cm−1
range on a Nicolet Impact 4100 FT-IR spectrometer using KBr pellets. Data are expressed in wavenumbers
1
(cm−1). H-, 13C- and 19F-NMR spectra were measured with a Varian Unity INOVA 300 MHz
spectrometer operating at 299.7, 282, and 75 MHz, respectively and were collected at 25 °C, using
D6-acetone for the deuterium lock. Chemical shifts are relative to TMS (δ = 0 (1H and 13C)) and CFCl3
(δ = 0 (19F)). Compounds were dissolved in deuterated acetone. Electronic Impact mass spectra were
obtained on a JEOL JMS-SX102A instrument. All reagents were commercially available and were used
as received.
3.2. General Procedure for the Synthesis of Fluorobenzylidene)hydrazine-1-carbothioamides 1–6
The corresponding Difluorobenzaldehyde (ca 5 mmol) was dissolved in ethanol (10 mL) at room
temperature and added dropwise to a stirred solution of hydrazinecarbothioamide (ca 5 mmol), in a 1:1
mixture of ethanol/water (30 mL) containing 0.2 mL of acetic acid (Scheme 1). The reaction mixture
was refluxed for 24 h. and then the solvent was reduced under vacuum to one third of the original
value, from which the product precipitated as white crystalline solid. Recrystallization from
ethanol/water (1:1) yielded the corresponding target product 1–5.
2-(2,4-Difluorobenzylidene)hydrazine-1-carbothioamide (1). From 2,4-difluorobenzaldehyde (0.8268 g,
1
3.84 mmol, 82%); colorless crystals, mp. 186–187 °C. H-NMR ((CD3)2CO) δ 7.95 (bs, 1H, NH2), δ
7.60 (bs, 1H, NH2), δ 10.65 (bs, 1H, NH), δ 8.37 (s, 1H, C2H), δ 8.22 (m, 1H, C5H), δ 7.09 (m, 2H,

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13
1
C7H and C8H); C-NMR ((CD3)2CO): δ (ppm) 179.77 (s, C-1), 163.78 (dd, C-6, JCF = 251.1 Hz,
3JCF = 12.4 Hz), 161.56 (dd, C-4, JCF = 253.0 Hz, JCF = 12.2 Hz), 134.32 (dd, C-2, JCF = 4.7 Hz),
128.21 (dd, C-8, 3JCF = 9.9 Hz, 3JCF = 4.3 Hz), 118.77 (dd, C-3, 2JCF = 10.2 Hz, 4JCF = 3.8 Hz), 112.17
(dd, C-7, 2JCF = 22.0, Hz, 4JCF = 3.5 Hz), 103.93 (t, C-5, 2JCF = 25.7 Hz). 19F{1H}-NMR ((CD3)2CO) δ
-107.78 (m, 1F, C2F), δ −117.72 (m, 1F, C4F). Analysis results for C8H7F2N3S: Found: C, 45.09; H,
3.02; N, 19.05; S, 15.28. Calculated: C, 44.66; H, 3.28; N, 19.52; S, 14.90. IR (KBr, ν cm−1): C
νas(NH2) 3400, νs(NH2) 3240, ν(NH) 3154, ν (C = N)/ν(C = C) 1600, ν(C-F) 1499, 1142, ν(C = S) 851.
MS-IE: [M]+ m/z 215 (100%).
1
3
3
2-(2,5-Difluorobenzylidene)hydrazine-1-carbothioamide (2). From 2,5-difluorobenzaldehyde (0.8050 g,
1
3.74 mmol, 81%); colorless crystals, mp. 187–188 °C. H-NMR ((CD3)2CO) δ 8.12 (bs, 1H, NH2), δ
7.63 (bs, 1H, NH2), δ 10.67 (bs, 1H, NH), δ 8.37 (s, 1H, C2H), δ 7.24 (m, 2H, C5H and C6H), δ 7.96
(m, 1H, C8H); 13C-NMR ((CD3)2CO): 180.91 (s, C-1), 159.90 (dd, C-7, 1JCF = 240.53 Hz, 4JCF = 2.1 Hz),
1
4
3
158.50 (dd, C-4, JCF = 246.5 Hz, JCF = 2.4 Hz), 134.73 (dd, C-2, JCF = 4.9 Hz), 124.56 (dd, C-3,
3
2
3
2JCF = 12.4 Hz, JCF = 8.6 Hz), 118.98 (dd, C-8, JCF = 25.3 Hz, JCF = 8.9 Hz), 118.32 (dd, C-6,
3
2
3
2JCF = 24.3 Hz, JCF = 8.8 Hz), 113.06 (dd, C-5, JCF = 26.0, Hz, JCF = 3.3 Hz). 19F{1H}NMR
((CD3)2CO) δ −119.77 (m, 1F, C2F), δ −128.40 (m, 1F, C5F). Analysis results for C8H7F2N3S: Found:
C, 44.35; H, 3.14; N, 19.53; S, 15.7. Calculated: C, 44.66; H, 3.28; N, 19.52; S, 14.90. IR (KBr, cm−1):
νas(NH2) 3405, νs(NH2) 3243, ν(NH) 3160, ν(C = N)/ν(C = C) 1601, ν(C-F) 1488, 1115, ν(C = S) 820.
MS-IE: [M]+ m/z 215 (10%).
2-(2,6-Difluorobenzylidene)hydrazine-1-carbothioamide (3). From 2,6-difluorobenzaldehyde (0.9200 g,
1
4.28 mmol, 92%); colorless crystals, mp. 195–196 °C. H-NMR ((CD3)2CO) δ 7.60 (bs, 1H, NH2), δ
7.50 (m, 1H, NH2), δ 10.66 (bs, 1H, NH), δ 8.32 (s, 1H, C2H), δ 7.11 (m, 2H, C5H and C7H), δ 7.50
13
1
(m, H, C6H); C-NMR ((CD3)2CO): δ (ppm) 180.81 (s, C-1), 162.02 (dd, C-4, JCF = 255.2 Hz,
3JCF = 6.5 Hz), 162.00 (dd, C-8, JCF = 255.2 Hz, JCF = 6.5 Hz), 133.44 (s, C-2), 132.46 (t, C-6,
1
3
3JCF = 10.8 Hz), 113.01 (m, C-5, C-7), 112.56 (t, C-3, JCF = 13.5 Hz). F{1H}-NMR ((CD3)2CO)
δ −113.02 (m, 1F, C2F), δ −113.02 (m, 1F, C6F). Analysis results for C8H7F2N3S: Found: C, 45.01; H,
3.34; N, 19.56; S, 15.75. Calculated: C, 44.66; H, 3.28; N, 19.52; S, 14.90. IR (KBr, cm−1): νas(NH2)
3430, 3410, νs(NH2) 3264, ν(NH) 3158, ν(C = N)/ν(C = C) 1601, ν(C-F) 1459, 1150, ν(C = S) 876.
MS-EI: [M]+ m/z 215 (70%).
2
19
2-(3,4-Difluorobenzylidene)hydrazine-1-carbothioamide (4). From 3,4-difluorobenzaldehyde (0.9500 g,
1
4.42 mmol, 95%); colorless crystals, mp. 196–197 °C. H-NMR ((CD3)2CO) δ 8.05 (bs, 1H, NH2), δ
7.58 (m, 1H, NH2), δ 10.56 (bs, 1H, NH), δ 8.15 (s, 1H, C2H), δ 7.58 (m, H, C4H), δ 7.38 (m, 1H,
13
1
C7H), δ 7.94 (m, 1H, C8H); C-NMR ((CD3)2CO): δ (ppm) 180.72 (s, C-1), 152.00 (dd, C-6, JCF
=
250.0 Hz, 2JCF = 13.1 Hz), 151.47 (dd, C-5, 1JCF = 246.3 Hz, 2JCF = 13.1 Hz), 140.99 (t, C-2, 4JCF = 2.4
3
4
3
4
Hz), 133.13 (dd, C-3, JCF = 6.5 Hz, JCF = 3.8 Hz), 125.82 (dd, C-8, JCF = 6.7 Hz, JCF = 3.4 Hz),
118.50 (d, C-4, 2JCF = 17.9 Hz), 115.82 (d, C-7, 2JCF = 18.7 Hz). 19F{1H}-NMR ((CD3)2CO) δ -136.97
(m, 1F, C3F), δ −138.82 (m, 1F, C4F). Analysis results for C8H7F2N3S: Found: C, 44.64; H, 3.21; N,
19.32; S, 14.82. Calculated: C, 44.66; H, 3.28; N, 19.52; S, 14.90. IR (KBr, ν cm−1): νas(NH2) 3426,

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νs(NH2) 3273, ν(NH) 3167, ν(C = N)/ν(C = C) 1609, ν(C-F) 1510, 1158, ν(C = S) 828. MS-EI: [M]+
m/z 215 (75%).
2-(3,5-Difluorobenzylidene)hydrazine-1-carbothioamide (5). From 3,5-difluorobenzaldehyde (0.8620
g, 4.01 mmol, 86%); colorless crystals, mp. 196–197 °C. 1H-NMR ((CD3)2CO) δ 8.13 (bs, 1H, NH2), δ
7.67 (m, 1H, NH2), δ 10.68 (bs, 1H, NH), δ 8.16 (s, 1H, C2H), δ 7.51 (m, H, C4H), δ 7.05 (tt, 1H, C6H,
4
13
3JHF = 9.1 Hz, JHF = 2.4 Hz), δ 7.51 (m, 1H, C8H); C-NMR ((CD3)2CO): δ (ppm) 179.92 (s, C-1),
163.27 (dd, C-5, 1JCF = 246.6 Hz, 3JCF = 12.9 Hz), 163.14 (dd, C-7, 1JCF = 246.6 Hz, 3JCF = 12.9 Hz),
4
3
2
139.74 (t, C-2, JCF = 3.6 Hz), 138.31 (t, C-3, JCF = 9.9 Hz), 109.88 (dd, C-4, C-8, JCF = 19.2 Hz,
4JCF = 7.3 Hz), 104.60 (t, C-6, JCF = 26.2 Hz). F{1H}-NMR ((CD3)2CO) δ -110.40 (m, 1F, C3F),
δ −110.40 (m, 1F, C5F). Mp. 199–200 °C. Analysis results for C8H7F2N3S: Found: C, 44.74; H, 3.18;
N, 19.79; S, 15.06. Calculated: C, 44.66; H, 3.28; N, 19.52; S, 14.90. IR (KBr, ν cm−1): νas(NH2) 3395,
νs(NH2) 3238, ν(NH) 3158, ν(C = N)/ν(C = C) 1605, ν(C-F) 1467, 1124, ν(C = S) 855. MS-EI: [M]+
m/z 215 (20%).
2
19
2-(4-Fluorophenyl)(phenyl)methylene)benzylidene)hydrazine-1-carbothioamide (6). From 4-fluoro-
1
phenyl-(phenyl)methanone (0.8648 g, 4.02 mmol, 86%); colorless crystals, mp 198–199 °C. H-NMR
((CD3)2CO) δ 8.12 (bs, 1H, NH2), δ 7.76 (m, 1H, NH2), δ 8.52 (bs, 1H, NH), δ 7.70 (m, H, C4H), δ
7.15 (tt, 2H, C5H, 3JHF = 9.9 Hz, 3JHH = 8.8 Hz and , C7H,3JHF = 9.9 Hz, 3JHH = 8.8 Hz), δ 7.70 (m, 1H,
C8H), δ 7.64 (m, 2H, C10H and C14H), δ 7.39 (m, 2H, C11H and C13H), δ 7.46 (m, 1H, C12H);
1
13C-NMR ((CD3)2CO): δ (ppm) 179.48 (s, C-1), 163.66 (d, C-6, JCF = 248.58 Hz), 148.36 (C-2),
136.84 (s, C-9), 133.28 (d, C-3, 4JCF = 3.1 Hz), 130.17 (s, C-12), 129.92 (s, C-10, C-14), 129.78 (d, C-
3
2
19
4, C-8 JCF = 8.5 Hz), 128.43 (s, C-11, C-13), 115.17 (d, C-5, C-7 JCF = 21.9 Hz). F {1H}NMR
((CD3)2CO) δ -111.36 (m, 1F, C4F). mp. 205 °C. Analysis results for C14H12FN3S: Found: C, 61.53;
H, 4.56; N, 15.47; S 11.71. Calculated: C, 61.52; H, 4.42; N, 15.37; S, 11.73. IR (KBr, ν cm−1): νas(NH2)
3430, νs(NH2) 3353, ν(NH) 3248, ν(C = N)/ν(C = C) 1595, ν(C-F) 1499, 1155, ν(C = S) 854. MS-EI:
[M]+ m/z 273 (14%).
3.3. X-ray Crystal Data for Compounds 1 to 6
Crystals 1–5 were studied using an Oxford Diffraction Gemini “A” diffractometer with a CCD area
detector (λMoKα = 0.71073 Å), while data for crystal 6 was collected on a Kappa CCD single crystal
diffractometer with Mo-Kα radiation (λ = 0.71073 Å).
Crystal data: 1 C8H7F2N3S, M = 215.23, monoclinic, P21/c, a = 12.0601(7), b = 8.1871(3),
c = 10.6170(6) Å, β = 112.431(7)°, V = 968.98(9) Å3, Z = 4, Dc = 1.475 g.cm−3, µ = 0.326 mm−1, 2296
independent measured reflections, F2 refinement, R1 = 0.0342, wR2 = 0.0811, goodness-of-fit = 0.896,
139 parameters, 0 restrains; 2 C8H7F2N3S, M = 215.23, monoclinic, P21/c, a = 10.3711(5),
b = 8.3331(2), c = 12.0732(5) Å, β = 111.923(6)°, V = 967.95(7) Å3, Z = 4, Dc = 1.477 g.cm−3,
µ = 0.327 mm−1, 2292 independent measured reflections, F2 refinement, R1 = 0.0377,wR2 = 0.1028,
goodness-of-fit = 1.026, 127 parameters, 0 restrains. 3 C8H7F2N3S, M = 215.24, monoclinic, P21/n,
a = 7.9792(6), b = 15.1661(12), c = 23.6599(19) Å, β = 90.553(8)°, V = 2863.0(4) Å3, Z = 4,
Dc = 1.498 g.cm−3, µ = 0.331 mm−1, 6848 independent measured reflections, F2 refinement, R1 = 0.0377,

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wR2 = 0.0934, goodness-of-fit = 1.025, 379 parameters, 0 restrains. 4 C8H7F2N3S, M = 215.23,
triclinic, P-1, a = 4.5780(2), b = 9.1499(4), c = 11.7475(7) Å, α = 81.555(5), β = 84.955(4),
γ = 77.972(4)°, V = 475.22(4) Å3, Z = 2, Dc = 1.504 g.cm−3, µ = 0.333 mm−1, 1880 independent
measured reflections, F2 refinement, R1 = 0.0312,wR2 = 0.0898, goodness-of-fit = 1.105,
127 parameters, 0 restrains. 5 C8H7F2N3S, M = 215.23, monoclinic, P21/c, a = 12.0810(8),
b = 8.1670(3), c = 10.7870(5) Å, β = 113.635(7)°, V = 975.03(9) Å3, Z = 4, Dc = 1.466 g.cm−3,
µ = 0.324 mm−1, 2309 independent measured reflections, F2 refinement, R1 = 0.0370, wR2 = 0.0990,
goodness-of-fit = 0.958, 127 parameters, 0 restrains. 6 C14H12FN3S, M = 273.33, monoclinic, C2/c,
a = 18.598(4) Å, b = 9.592(2) Å, c = 16.813(3)Å, β = 111.43(3)°, V = 2791.7(1)Å3, Z = 8,
Dc = 1.301 g.cm−3, µ = 0.232 mm−1, 2466 independent measured reflections, F2 refinement,
R1 = 0.0717, wR2 = 0.2334, goodness-of-fit = 1.040, 172 parameters, 0 restrains.
4. Conclusions
As expected, the reactions of hydrazinecarbothioamide with the fluorobenzaldehides R-CHO
(R = 2,4-C6H3F2, R = 2,5-C6H3F2, R = 2,6-C6H3F2, R = 3,4-C6H3F2, R = 3,5-C6H3F2) or the fluoroacetone
4-C6H4F-C(Ph)O give rise to the six corresponding examples of fluorinated thiosemicarbazones, with
very high yields. The x-ray diffraction molecular and crystal structures obtained for all six compounds,
confirms that they all have an E configuration with the sulfur atom trans to the iminic nitrogen.
The NH2 group at the carbothioamide moiety exhibit hydrogens with two different magnetic behavior
due to the double bond character in the C-N bond restricting the free rotation of this bond. In addition,
the crystal network structured by these compounds shows the presence of π interactions between some
aromatic rings of neighboring molecules and several intermolecular interactions between atoms of
hydrogen and sulfur or fluorine atoms.
Supplementary Materials
Supplementary Materials include copies of IR, MS, 1H-, 13C- and 19F-NMR spectra for compounds 1–6.
These materials can be accessed at: http://www.mdpi.com/1420-3049/18/10/13111/s1.
Acknowledgments
We are grateful to DGAPA-UNAM (IN217611) and CONACYT (CB-2012-01/177498) for
financial support.
Conflicts of Interest
The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds are available from the authors.
© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).