Synthesis and characterization of N-phosphorylated thioureas RNHC(S)NHP(O)(OiPr)2 (R = 2-MeC6H4, 2,6-Me 2C6H3, 2,4,6-Me3C6H 2)

Article abstract of DOI:10.1007/s12039-010-0046-3

Reaction of O,O'-diisopropylphosphoric acid isothiocyanate (iPrO) ₂P(O)NCS with 2- methylaniline 2-MeC₆H₄NH ₂, 2-dimethylaniline 2,6-Me₂C₆H ₃NH₂ or 2,4,6-trimethylanil

Full text of DOI:10.1007/s12039-010-0046-3

J. Chem. Sci., Vol. 122, No. 3, May 2010, pp. 409–413. © Indian Academy of Sciences.
Synthesis and characterization of N-phosphorylated thioureas
RNHC(S)NHP(O)(OiPr) (R = 2-MeC H , 2,6-Me C H ,
2
6
4
2
6
3
2,4,6-Me C H )
3 6 2
a,
a
b
DAMIR A SAFIN *, MARIA G BABASHKINA , MICHAEL BOLTE and AXEL KLEIN
a
a
Institut für Anorganische Chemie, Universität zu Köln, Greinstrasse 6, D-50939 Köln, Germany
b
Institut für Anorganische Chemie J.-W.-Goethe-Universität, Frankfurt/Main, Germany
e-mail: damir.safin@ksu.ru
MS received 29 August 2009; revised 4 January 2010; accepted 12 January 2010
Abstract. Reaction of O,O′-diisopropylphosphoric acid isothiocyanate (iPrO) P(O)NCS with 2-
2
methylaniline 2-MeC H NH , 2,6-dimethylaniline 2,6-Me C H NH or 2,4,6-trimethylaniline 2,4,6-
6 4 2 2 3
6
2
I
Me C H NH leads to the N-phosphorylated thioureas RNHC(S)NHP(O)(OiPr) (R = 2-MeC H -, HL ;
3
6
2
2
2
6
4
II
2,6-Me C H -, HL ; 2,4,6-Me C H -, HL ). The new compounds were investigated by H and P{ H}
III
1
31
1
2
6
3
3
6
2
III
NMR spectroscopy, and microanalysis. The molecular structure of the thiourea HL was elucidated by
III
single crystal X-ray diffraction analysis. Single crystal X-ray diffraction studies showed HL forms both
intra- and intermolecular hydrogen bonds, which in turn leads to the formation of polymeric chains. One
of the intermolecular hydrogen bonds is of the type N–H⋅⋅⋅S. Moreover, the formation of intermolecular
6
C–H⋅⋅⋅η -phenyl interactions was established.
Keywords. Phosphorylthiourea; crystal structure; NMR spectroscopy; hydrogen bond.
1. Introduction
This contribution is a continuation of our previ-
ously started investigations on the synthesis and
characterization of N-(thio)phosphorylated (thio)
Amidophosphates RC(S)NHP(X)R′ and the related
N-(thio)phoshorylated thioureas RNHC(S)NHP(X)R′
2
12
amides and (thio)ureas. Here, we report the syn-
2
(R = various alkyl or aryl groups; X = O or S;
R′ = OR) have attracted the attention of researchers
in the last three decades mainly due to their ability
to form stable chelate complexes with IB, IIB, and
VIIIB group transition metal cations. These com-
pounds offer a number of very interesting applica-
tions. Some of them exhibit remarkable antiviral
thesis and characterization of the three N-
phosphorylated thioureas RNHC(S)NHP(O)(OiPr)2
I
II
(R = 2-MeC6H4-, HL ; 2,6-Me2C6H3-, HL ; 2,4,6-
III
Me3C6H2-, HL ).
2. Experimental
1
activity, they can be used as stationary phases for
I–III
2.1 Synthesis of HL
2
GLC, as well as components of ion-selective elec-
3–6
7–9
trodes,
extractants,
and masking reagents in A solution of 2-methylaniline, 2,6-dimethylaniline
10
analytical chemistry. or 2,4,6-trimethylaniline (5 mmol, 0⋅54, 0⋅61 or
Furthermore, RC(S)NHP(X)R′ can form various 0⋅68 g) in anhydrous CH2Cl2 (15 mL) was treated
2
intra- and intermolecular bonds. Formation of hy- under vigorous stirring with
a
solution of
drogen bonds of the type N–H⋅⋅⋅S is also possible. A (iPrO)2P(O)NCS (6 mmol, 1⋅34 g) in the same sol-
detailed study on such compounds might be useful vent. The mixture was stirred for 1 h. The solvent
to provide information on such a type of interaction was then removed under vacuum, and the product
because the N–H⋅⋅⋅S hydrogen bond is not abun- was purified by recrystallization from a 1 : 5 (v/v)
11
dant. However, this type of hydrogen bonding in- mixture of dichloromethane and n-hexane.
12
teractions is rather typical for RC(S)NHP(X)R′ .
2
I
2.1a HL Yield: 1⋅42 g (86%); m.p.: 72°C; Anal.
Calcd. for C14H23N2O3PS (330⋅38): C, 50⋅90; H,
7⋅02; N, 8⋅48; Found: C, 50⋅96; H, 6⋅95; N, 8⋅52;
*For correspondence
409

410
Damir A Safin et al
1
3
H NMR δ (ppm): 1⋅39 (d, JH,H = 6⋅1 Hz, 12H, CH3, riding models. H atoms bound to N were freely re-
iPr), 2⋅31 (s, 3H, CH3, Me), 4⋅83 (d, sept, fined.
CCDC 737532 (HL ) contains the supplementary
3
3
JPOCH = 7⋅1 Hz, JH,H = 6⋅0 Hz, 2H, OCH), 6⋅94–
III
7⋅61 (m, overlapping with the solvent signal, crystallographic data. These data can be obtained
C6H4 + PNH), 9⋅42 (s, 1H, NH); P{ H} NMR δ free of charge via http://www.ccdc.cam.ac.uk/
31
1
(ppm): –6⋅4.
conts/retrieving.html, or from the Cambridge Crys-
tallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or
e-mail: deposit@ccdc.cam.ac.uk.
II
2.1b HL Yield: 1⋅62 g (94%); m.p.: 89°C; Anal.
Calcd. for C15H25N2O3PS (344⋅41): C, 52⋅31; H,
1
7⋅32; N, 8⋅13; Found: C, 52⋅20; H, 7⋅37; N, 8⋅05; H
3
NMR δ (ppm): 1⋅43 (d, JH,H = 6⋅1 Hz, 6H, CH3,
3. Results and discussion
3
iPr), 1⋅46 (d, JH,H = 6⋅2 Hz, 6H, CH3, iPr), 2⋅32 (s,
3
I–III
6H, CH3, Me), 4⋅87 (d, sept, JPOCH = 7⋅2 Hz,
The compounds HL
were synthesized by treating
3
JH,H = 6⋅1 Hz, 2H, OCH), 7⋅09–7⋅36 (m, overlapped
2-methylaniline, 2,6-dimethylaniline or 2,4,6-
with the solvent signal, C6H3 + PNH), 9⋅59 (s, 1H,
trimethylaniline with the isothiocyanate (iPrO)2
31
1
I
NH) ppm. P{ H} NMR δ (ppm): –6⋅3.
P(O)NCS (scheme 1) in good yields for HL and
II
III
HL and reasonable yield for HL . Their composi-
III
2.1c HL Yield: 1⋅29 g (72%); m.p.: 97°C; Anal.
tions were proved by microanalysis data (see Ex-
I–III
Calcd. for C16H27N2O3PS (358⋅44): C, 53⋅62; H,
perimental Section). The formation of HL
by the
1
7⋅59; N, 7⋅82; Found: C, 53⋅71; H, 7⋅68; N, 7⋅89; H
NMR δ (ppm): 1⋅42 (d, JH,H = 6⋅2 Hz, 12H, CH3,
addition reaction of the NH2 group of the corre-
sponding amine and (iPrO)2P(O)NCS was proved by
the NMR data.
3
iPr), 2⋅24 (s, 6H, CH3, Me), 2⋅29 (s, 3H, CH3, Me),
3
3
31 1
The P{ H} NMR spectra of HL
I–III
4⋅77 (d, sept, JPOCH = 6⋅8 Hz, JH,H = 6⋅2 Hz, 2H,
OCH), 6⋅91 (s, 2H, C6H2), 7⋅02 (br, s, 1H, PNH),
each contain
a singlet signal at –6⋅4, –6⋅3 and –5⋅9 ppm, respec-
tively, which is typical for N-phosphoryl thioureas.
31
1
11
10⋅07 (s, 1H, NH); P{ H} NMR δ (ppm): –5⋅9.
1
The H NMR spectra of the thioureas contain one set
I
of signals for the iPr protons: one doublet (HL and
2.2 Physical measurements
III
II
HL ) or two doublets (HL ) for the CH3 protons at
1.39–1.46 ppm and a doublet of septets for the CH
protons in the range of 4⋅77–4⋅87 ppm. The Me pro-
ton signals of the aryl substituents were observed at
2⋅24–2⋅32 ppm. The aromatic ring and PNH proton
signals are at 6⋅91–7⋅61 ppm. Signals for the arylNH
protons in the spectra are at 9⋅42–10⋅07 ppm. These
signals are low-field shifted probably due to the
formation of hydrogen bonds of the type arylN–
H⋅⋅⋅O=P, as has been observed for related thiophor-
sphorylated thioureas.
NMR spectra in CDCl3 were obtained on a Bruker
1
Avance 300 MHz spectrometer at 25°C. H and
31
1
P{ H} NMR spectra were recorded at 299⋅948 and
121⋅420 MHz, respectively. Chemical shifts are
reported with reference to SiMe4 ( H) and 85%
1
31
1
H3PO4 ( P{ H}). Elemental analyses were performed
on a CHNS HEKAtech EuroEA 3000 analyser.
2.3 Crystal structure determination and refinement
III
Crystals of HL were obtained by recrystal-
III
lization from dichloromethane–n-hexane solution.
The crystal structure data is collected in table 1,
while the molecular conformation and geometric pa-
rameters are shown in figure 1.
The X-ray data for HL were collected on STOE
IPDS-II
diffractometer
with
graphite-mono-
chromatized Mo-K radiation generated by fine-
α
focus X-ray tube operated at 50 kV and 40 mA. The
images were indexed, integrated and scaled using
III
The compound HL crystallizes in the space
13
the X-ray data reduction package. Data were cor-
group P–1. The asymmetric unit contains two inde-
14
pendent molecules. The parameters of the C=S,
rected for absorption using the PLATON program.
III
C–N, P–N and P=O bonds observed for HL (fig-
The structures were solved by direct methods using
15
the SHELXS-97 program and refined first isot-
ure 1) are in the typical range for N-phosphorylated
12
thiourea derivatives. The S–C–N–P backbone in
ropically and then anisotropically using SHELXL-
15
97. Hydrogen atoms were revealed from Δρ maps
the crystal phase has a E-conformation. The aryl
fragment is almost orthogonal to the N–C(S)–N–P
and those bound to C were refined using appropriate

Synthesis and characterization of N-phosphorylated thioureas RNHC(S)NHP(O)(OiPr)
411
2
Scheme 1.
III
Table 1. Crystal structure and data refinement parameters for HL .
Empirical formula
–1
Formula weight (g mol )
C H N O PS
16 27 2 3
358⋅43
Temperature (K)
Crystal system
Space group
a (Å)
173(2)
triclinic
P–1
10⋅6334(7)
13⋅4890(8)
b (Å)
c (Å)
15⋅7710(10)
α (°)
82⋅491(5)
β (°)
70⋅663(5)
γ (°)
3
V (Å )
67⋅113(5)
1966⋅4(2)
Z
4
–3
(Mg m )
D
1⋅211
calc
–1
Absorption coefficient, μ (mm )
F(000)
0⋅260
768
Crystal size (mm)
0⋅32 × 0⋅26 × 0⋅21
3⋅55–25⋅59
Recording range, θ (°)
Number of recorded reflections
Number of recorded independent reflections
Final R indices [I > 2 sigma(I)]
R indices (all data)
21017
7336 [R(int) = 0⋅0465]
R1 = 0⋅0389, wR2 = 0⋅0937
R1 = 0⋅0568, wR2 = 0⋅0989
0⋅951
S
III
Table 2. Hydrogen bond lengths (Å) and angles (°) for HL .
D–H⋅⋅⋅A
d(D–H)
d(H⋅⋅⋅A)
d(D⋅⋅⋅A)
∠(DHA)
N(1)–H(1)⋅⋅⋅S(1A)#1
N(2)–H(2)⋅⋅⋅O(3)
0⋅85(3)
0⋅82(3)
0⋅82(3)
0⋅82(3)
0⋅83(3)
0⋅79(3)
0⋅79(3)
0⋅79(3)
2⋅51(3)
2⋅22(3)
2⋅18(3)
2⋅27(3)
2⋅50(3)
2⋅30(3)
2⋅19(3)
2⋅22(2)
3⋅328(2)
2⋅920(2)
2⋅811(10)
2⋅927(2)
3⋅317(2)
2⋅943(2)
2⋅761(8)
2⋅874(2)
164(2)
143(2)
133(2)
136(2)
166(2)
139(2)
130(2)
141(2)
N(2)–H(2)⋅⋅⋅O(3')
N(2)–H(2)⋅⋅⋅O(3A)
N(1A)–H(1A)⋅⋅⋅S(1)#2
N(2A)–H(2A)⋅⋅⋅O(3)
N(2A)–H(2A)⋅⋅⋅O(3′)
N(2A)–H(2A)⋅⋅⋅O(3A)
Symmetry transformations used to generate equivalent atoms: #1 x + 1, y, z; #2 x – 1,
y, z.
plane. The crystal structure is stabilized by bonds of the types N(2)–H(2)⋅⋅⋅O(3A)–P(1A) and
intramolecular hydrogen bonds of the types N(2)– N(2A)–H(2A)⋅⋅⋅O(3)[O(3')]–P(1) (figure 1, table 2).
H(2)⋅⋅⋅O(3)[O(3′)]–P(1) and N(2A)–H(2A)⋅⋅⋅O(3A)– Yet another mode of aggregation is found for this
P(1A) (figure 1, table 2). Two independent mole- dimer. Two independent molecules exhibit interac-
cules form a dimer due to intermolecular hydrogen tions between the OCH hydrogen atoms and the aryl

412
Damir A Safin et al
III
Figure 1. View on the crystal structure of HL . Ellipsoids are drawn at the 50% probability
level. H-atoms, not involved in hydrogen bonding, are omitted for clarity. Selected bond
distances (Å) and angles (°): P(1)–O(3) 1⋅482(2), P(1)–O(3′) 1⋅391(7), P(1)–N(1) 1⋅656(2),
S(1)–C(1) 1⋅675(2), N(1)–C(1) 1⋅383(2), N(2)–C(1) 1⋅333(2), P(1A)–O(3A) 1⋅4656(14),
P(1A)–N(1A) 1⋅658(2), S(1A)–C(1A) 1⋅673(2), N(1A)–C(1A) 1⋅378(2), N(2A)–C(1A)
1⋅334(2); O(3)–P(1)–N(1) 113⋅29(9), O(3')–P(1)–N(1) 116⋅3(4), C(1)–N(1)–P(1) 128⋅61(14),
N(2)–C(1)–N(1) 117⋅1(2), N(1)–C(1)–S(1) 119⋅45(14), N(2)–C(1)–S(1) 123⋅44(13), O(3A)–
P(1A)–N(1A) 113⋅02(8), C(1A)–N(1A)–P(1A) 128⋅27(14), N(2A)–C(1A)–N(1A) 116⋅8(2),
N(1A)–C(1A)–S(1A) 120⋅05(14), N(2A)–C(1A)–S(1A) 123⋅11(14).
6 III
Table 3. Selected C–H⋅⋅⋅η -phenyl interactions for HL .
a
C–H
Cg(J)
H⋅⋅⋅Cg (Å)
C⋅⋅⋅Cg (Å)
C–H⋅⋅⋅Cg (°)
#1
C(5)–H(5)
Cg(2)
2⋅96
2⋅53
3⋅876(3)
3⋅497(3)
153
163
#1
C(5A)–H(5A)
Cg(1)
a
Cg refers to the ring center of gravity and the numbers represent the rings
involved in the interactions.
b
Symmetry codes: #1 x, y, z. Cg(1): C(11)–C(12)–C(13)–C(14)–C(15)–C(16);
Cg(2): C(11A)–C(12A)–C(13A)–C(14A)–C(15A)–C(16A).
rings of an adjacent molecule (table 3). Furthermore,
Single crystal X-ray diffraction studies showed
III
dimers form polymeric chains due to the intermo- that the thiourea HL forms both intra- and inter-
lecular hydrogen bonds of the types N(1)– molecular hydrogen bonds in the solid, which leads
H(1)⋅⋅⋅S(1A)#1–C(1A)#1 and N(1A)–H(1A)···S(1)#2– to the formation of polymeric chains. Moreover,
6
C(1)#2 (figure 1, table 2).
intermolecular C–H⋅⋅⋅η -phenyl interactions were
established in HL .
III
4. Conclusions
Acknowledgements
In summary, we have demonstrated the syntheses of
This work was supported by the Russian Science Sup-
port Foundation. D A S and M G B thank Deutscher
Akademischer Austausch Dienst (DAAD) for the
scholarships (Forschungsstipendien 2008/2009).
I–III
three new N-phosphorylated thioureas HL
addition of phosphorylisothiocyanate to the corre-
sponding amine.
by

Synthesis and characterization of N-phosphorylated thioureas RNHC(S)NHP(O)(OiPr)
413
2
7. Navratil O, Herrmann E, Chau N T T, Tea Ch and
Smola J 1993 Collect. Czech. Chem. Commun. 58 798
8. Luckay R C, Sheng X, Strasser C E, Raubenheimer H
G, Safin D A, Babashkina M G and Klein A 2009
Dalton Trans. 4646
References
1. Zabirov N G, Pozdeev O K, Shamsevaleev F M,
Cherkasov R A and Gilmanova G Kh 1989 Khim.
Farm. Zh. (USSR) 23 600
9. Luckay R C, Sheng X, Strasser C E, Raubenheimer H
G, Safin D A, Babashkina M G and Klein A 2009
Dalton Trans. 8227
2. Vetrova Z P, Zabirov N G, Shuvalova T N,
Smerkovich L S, Ivanova L A, Golberg A K and
Karabanov N T 1992 Zh. Obshch. Khim. (USSR) 62
1079
10. Zimin M G, Lazareva G A, Saveleva N I, Islamov R
G, Zabirov N G, Toropova V F and Pudovik A N
1982 Zh. Obshch. Khim. (USSR) 52 1776
3. Shaidarova L G, Gedmina A V, Brusko V V, Zabirov
N G, Ulakhovich N A and Budnikov G K 2001 Anal.
Sci. 17 i957
11. Kumara Swamy K C, Kumaraswamy S, Raja S and
Kumar K S 2001 J. Chem. Crystallogr. 31 51
12. Sokolov F D, Brusko V V, Zabirov N G and Cher-
kasov R A 2006 Curr. Org. Chem. 10 27
4. Kutyreva M P, Zabirov N G, Brusko V V and Ulak-
hovich N A 2001 Anal. Sci. 17 i1049
5. Shaidarova L G, Gedmina A V, Brusko V V, Zabirov
N G, Ulakhovich N A and Budnikov G K 2002 Russ.
J. Appl. Chem. 75 919
13. Stoe and Cie 2001 X-Area, Area-Detector Control
and Integration Software. Stoe and Cie (Darmstadt,
Germany)
6. Shaidarova L G, Gedmina A V, Ulakhovich N A,
Budnikov G K and Zabirov N G 2002 Russ. J. Gen.
Chem. 72 1565
14. Spek A L 2009 Acta Crystallogr. A65 148
15. Sheldrick G M 2008 Acta Crystallogr. A64 112.