Reactions of l, 3-diethyl-2-thiobarbituric acid with aldehydes: Formation of arylbis(l, 3-diethyl-2-thiobarbitur-5-yl)methanesf and crystallographic evidence for ground state polarisation in l, 3-diethyl-5-[4-(dimethylamino)benzylidene]-2-thiobarbituric a

Article abstract of DOI:10.1039/a904015c

The reactions of 1, 3-diethyl-2-thiobarbituric acid (detba) in ethanol at room temperature with 4-(dimethylamino)benzaldehyde (dmabza) or cinnamaldehyde afford the Knoevenagel products 3 and 4, respectively. Under identical conditions, pyridine-4-carbalde

Full text of DOI:10.1039/a904015c

View Article Online / Journal Homepage / Table of Contents for this issue
Reactions of 1,3-diethyl-2-thiobarbituric acid with aldehydes:
formation of arylbis(1,3-diethyl-2-thiobarbitur-5-yl)methanes†
and crystallographic evidence for ground state polarisation in
1
,3-diethyl-5-[4-(dimethylamino)benzylidene]-2-thiobarbituric acid
a
a
a
b
c
Jason Adamson, Benjamin J. Coe,* Helen L. Grassam, John C. Jeffery, Simon J. Coles
c
and Michael B. Hursthouse
a
Department of Chemistry, University of Manchester, Oxford Road, Manchester,
UK M13 9PL. E-mail: b.coe@man.ac.uk
Department of Chemistry, University of Bristol, Cantock’s Close, Bristol, UK BS8 1TS
EPSRC X-ray Crystallography Service, Department of Chemistry, University of
b
c
Southampton, Highfield, Southampton, UK SO17 1BJ
Received (in Cambridge, UK) 19th May 1999, Accepted 14th July 1999
The reactions of 1,3-diethyl-2-thiobarbituric acid (detba) in ethanol at room temperature with 4-(dimethylamino)-
benzaldehyde (dmabza) or cinnamaldehyde afford the Knoevenagel products 3 and 4, respectively. Under identical
conditions, pyridine-4-carbaldehyde, 4-methoxybenzaldehyde, benzaldehyde, 4-cyanobenzaldehyde, 4-nitrobenz-
aldehyde and 4-ferrocenylbenzaldehyde yield exclusively the arylbis(1,3-diethyl-2-thiobarbitur-5-yl)methane Michael
adducts 2, 5, 6, 7, 8 and 9, respectively. Although 3 can be forced to react further by treatment with excess detba in
refluxing ethanol, the product 10 is unstable in solution and readily reverts to 3. The stability of 4 is attributed to
extended conjugation, and it is likely that the pronounced difference in reactivity between dmabza and the other
arylaldehydes arises primarily from electronic factors, i.e. the strongly electron donating effect of the -NMe2
substituent. Single crystal X-ray structures have been determined for the products 3 and 6. The structure of 6 con-
firms the formation of the Michael adduct and shows that both of the detba rings are present in mixed keto–enol
forms, although the oxygens differ slightly in their degree of enolic character. The bond distances in 3 provide clear
evidence for extensive ground state polarisation, in accord with the marked molecular nonlinear optical properties
n
of the analogous -N( Bu) compound.
2
Introduction
in further studies of the reactions of detba with aldehydes,
and the results of these investigations are reported herein,
including crystallographic characterisations of two of the
products.
It is well established that barbituric acid (ba) and 2-thio-
barbituric acid (tba) undergo Knoevenagel condensations with
1,2
aldehydes to give 5-substituted derivatives. Such reactions
have attracted interest recently for the preparation of com-
pounds which have potential utility in two disparate fields of
research. In the realm of biological chemistry, work involving3
artificial, hydrogen-bonding receptors for barbiturate drugs
has inspired the preparation of barbiturate derivatives possess-
4
ing specific host–guest recognition properties. Barbiturate
groups are strongly electron-withdrawing because they gain
5
aromatic stabilisation upon reduction. This property has been
exploited in the preparation of molecules which possess very
pronounced quadratic non-linear optical (NLO) properties,
of interest for potential applications in opto-electronic and
6
photonic technologies.
The 1:1 reaction of 4Ј-methyl-2,2Ј-bipyridyl-4-carbaldehyde
with ba in refluxing ethanol affords the Knoevenagel product
4
in high yield. As part of an ongoing investigation into the
7
NLO properties of organotransition metal complexes, we
hence sought to prepare the potential ligand 1,3-diethyl-5-(4-
picolylidene)-2-thiobarbituric acid (1) via reaction of 1,3-
diethyl-2-thiobarbituric acid (detba) with pyridine-4-carbalde-
6b
hyde. However, using standard conditions, we instead isolated
the compound 4-pyridylbis(1,3-diethyl-2-thiobarbitur-5-yl)-
methane (2). This unexpected outcome stimulated us to engage
Results and discussion
Syntheses
It is clear that compound 2 results from the Michael addition
of a second molecule of detba across the vinyl group of 1.
Variation of the reaction stoichiometry and/or temperature
†
IUPAC name for arylbis(1,3-diethyl-2-thiobarbitur-5-yl)methane is
arylbis(1,3-diethyl-2-thio-4,6-dioxohexahydro-5-pyrimidyl)methane.
J. Chem. Soc., Perkin Trans. 1, 1999, 2483–2488
2483

View Article Online
Table 1 Crystallographic data and refinement details for compounds 3 and 6
3
6
Formula
M
C H N O S
331.43
C H N O S
4 2
488.61
1
7
21
3
2
23 28
4
Crystal system
Space group
Triclinic
P1
Monoclinic
¯
P2 /c
1
a/Å
b/Å
c/Å
α/Њ
β/Њ
γ/Њ
7.913(5)
8.920(2)
9.845(2)
26.878(3)
10.040(3)
10.363(5)
88.87(4)
79.58(4)
85.40(4)
807.1(6)
2
92.23(2)
3
U/Å
Z
2358.6(4)
4
1.376
293(2)
Ϫ3
D /Mg m
1.364
173(2)
c
T/K
λ/Å
F(000)
µ/mm
0.710 73 (Mo-Kα)
352
0.214
0.710 73 (Mo-Kα)
1032
0.264
Ϫ1
Scan type
θ range/Њ
ꢀ and ω
2.00–27.48
ꢀ and ω
5.11–23.24
h, k, l ranges
Ϫ10/10, Ϫ12/13, Ϫ13/12
8147
3650 (0.0349)
3650/0/212
Ϫ9/9, Ϫ10/10, Ϫ29/29
22873
3233 (0.0549)
3233/0/310
Reflections collected
Independent reflections (Rint
Data/restraints/parameters
Final R indices [I > 2σ(I)]
Final R indices (all data)
)
a,b
R = 0.0443, wR = 0.1086
R = 0.0420, wR = 0.1305
1
2
1
2
R = 0.0623, wR = 0.1127
R = 0.0525, wR = 0.1399
1
2
1
2
b
Weighting factors (x, y)
0.0616, 0
0, 0
Goodness of fit, S
Peak and hole, e Å
0.909
0.532, Ϫ0.302
1.111
0.161, Ϫ0.250
Ϫ3
a
2
Structures were refined on F using all data; the value of R is given for comparison with older refinements based on F with a typical threshold of
o
1
o
b
2
2
2
2
2
1/2
2
2
2
1/2
F > 4σ(F ). wR = [Σw(F Ϫ F ) /Σw(F ) ] ; S = [Σw(Fo Ϫ F ) /(M Ϫ N)] , where M = number of reflections and N = number of parameters;
w
o
o
2
o
c
o
c
Ϫ1
2
2
2
2
2
= [σ (F ) ϩ (xP) ϩ yP] and P = [max(F , 0) ϩ 2F ]/3.
o
o
c
Fig. 1 Structural representation of compound 3 (50% probability
ellipsoids).
affect the yield of 2, but we have not detected any traces of 1.
The formation of Michael adducts often follows Knoevenagel
1
condensations, but this has not been observed previously with
tba or its N-alkyl derivatives. Furthermore, reactions of ba
with arylaldehydes also typically afford Knoevenagel products,
the only reported exception being salicylaldehyde. However, no
Fig. 2 Structural representation of compound 6 (50% probability
ellipsoids).
8
explanation was offered for the production of the Michael
8
adduct in the latter case.
tate pure 3 in high yield, and a similar reaction occurs with
cinnamaldehyde to afford 4. However, reactions with benzalde-
hyde or 4-substituted benzaldehydes under identical conditions
precipitate the new arylbis(1,3-diethyl-2-thiobarbitur-5-yl)-
methanes 5–9 in good yields. Concentration of the filtrates
affords further quantities of 5–9, but no traces of the Knoeve-
nagel products have been detected, irrespective of the reaction
stoichiometries. The compound 9 is unstable when dissolved in
various common solvents, rapid colour changes from golden to
olive green suggesting air oxidation of the ferrocenyl moiety.
The isolation of a Knoevenagel product 4 from the reaction
of detba with cinnamaldehyde is consistent with previous
The Knoevenagel product derived from detba and 4-(di-
methylamino)benzaldehyde (dmabza), 1,3-diethyl-5-[4-(di-
methylamino)benzylidene]-2-thiobarbituric acid (3), was first9
prepared as part of an investigation into merocyanine dyes.
Compound 3 was obtained in 80% crude yield from a 1:1 reac-
tion in refluxing ethanol with piperidine as a base catalyst.
Other workers have since prepared similar derivatives of ba or
,3-dimethylbarbituric acid by reaction with benzaldehydes in
refluxing water or ethanol, and related derivatives of detba
have been synthesised in benzene with morpholine as catalyst.
We have found that detba condenses with dmabza at room
temperature in ethanol with no additional catalyst to precipi-
1
10
2
6
reports involving other vinylaldehydes. Presumably these 1:1
2
484
J. Chem. Soc., Perkin Trans. 1, 1999, 2483–2488

View Article Online
Table
2
Selected interatomic distances (Å) and angles (Њ) for
compounds 3 and 6
withdrawing pyridyl group will enhance the Lewis acidity of 1,
and a similar situation pertains to the analogues of 3 bearing
H, -CN or -NO 4-substituents, leading to the formation of 6,
-
2
3
7
or 8, respectively. Although the methoxy or ferrocenyl groups
C(1)–C(2)
C(1)–C(6)
C(1)–C(7)
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(4)–N(4)
C(5)–C(6)
C(7)–C(11)
C(11)–C(12)
1.422(3)
1.419(3)
1.430(3)
1.369(3)
1.419(3)
1.421(3)
1.355(2)
1.366(3)
1.377(3)
1.464(3)
C(11)–C(16)
C(12)–N(13)
C(12)–O(12)
C(14)–N(15)
C(14)–S(14)
C(16)–O(16)
N(4)–C(41)
N(4)–C(42)
N(13)–C(14)
N(15)–C(16)
1.459(2)
1.414(2)
1.225(2)
1.384(2)
1.667(2)
1.221(2)
1.466(2)
1.463(2)
1.378(2)
1.411(2)
are moderately electron-donating, they clearly do not stabilise
the Knoevenagel products sufficiently to prevent further reac-
tion. Compound 3 can be forced to react further by treatment
with excess detba in refluxing ethanol, but the Michael adduct
1
0 is unstable in solution and readily reverts to 3, as shown by
proton NMR and UV-visible spectra. The observed reactivity
differences are hence not simply due to the poor solubility of 3
in ethanol.
C(2)–C(1)–C(7)
C(2)–C(3)–C(4)
C(3)–C(2)–C(1)
C(4)–N(4)–C(41)
C(4)–N(4)–C(42)
C(5)–C(4)–C(3)
C(5)–C(6)–C(1)
C(6)–C(1)–C(2)
C(6)–C(1)–C(7)
C(6)–C(5)–C(4)
C(7)–C(11)–C(12)
C(7)–C(11)–C(16)
C(11)–C(7)–C(1)
128.5(2)
122.0(2)
121.6(2)
120.9(2)
121.1(2)
117.0(2)
123.4(2)
115.6(2)
115.8(2)
120.3(2)
115.6(2)
126.2(2)
138.5(2)
C(14)–N(15)–C(16) 124.6(2)
Crystallographic and spectroscopic studies
C(16)–C(11)–C(12)
C(42)–N(4)–C(41)
N(4)–C(4)–C(3)
N(4)–C(4)–C(5)
118.1(2)
117.8(2)
121.6(2)
121.4(2)
Many X-ray crystal structures of ba derivatives have been
3,10,12
reported,
but the only ones of tba derivatives are those of
1
,3-diethyl-5-[5-(N,N-diethylamino)penta-2,4-dienylidene]-2-
N(13)–C(12)–C(11) 117.4(2)
N(13)–C(14)–N(15) 116.6(2)
13
thiobarbituric acid (11), and 1,3-diethyl-5-(hydroxyimino)-
2
14
-thiobarbituric acid. We have undertaken single crystal
N(13)–C(14)–S(14)
N(15)–C(14)–S(14)
122.08(14)
121.3(2)
X-ray diffraction studies of 3 and 6, and representations of
the molecular structures are shown in Fig. 1 and 2, respec-
tively.
N(15)–C(16)–C(11) 117.2(2)
O(12)–C(12)–C(11) 123.9(2)
O(12)–C(12)–N(13) 118.7(2)
O(16)–C(16)–C(11) 125.1(2)
O(16)–C(16)–N(15) 117.7(2)
The structure of 6 confirms the formation of the Michael
adduct and shows that both of the detba rings are present in
mixed keto–enol forms. The enolic protons (Ha and Hb) were
located from the difference Fourier map and freely refined.
Investigation of the bond lengths (Table 2) around these hydro-
gens shows that the oxygens differ slightly in their degree of
enolic character. The bond distances O(2)–Ha and O(3)–Hb are
significantly shorter than O(4)–Ha and O(1)–Hb, respectively,
showing that O(2) and O(3) possess greater enolic properties
than O(4) and O(1), respectively. Furthermore, C(9)–O(1) and
C(23)–O(4) are shorter than C(17)–O(3) and C(15)–O(2),
respectively, with all four of these separations being of inter-
mediate length between the ideal values for the keto and enol
forms. Indeed, their average value (1.287(6) Å) is ca. 0.06 Å
C(14)–N(13)–C(12) 124.7(2)
6
C(1)–C(2)
C(1)–C(8)
C(1)–C(16)
C(2)–C(3)
C(2)–C(7)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
C(6)–C(7)
C(8)–C(9)
C(8)–C(15)
C(16)–C(17)
C(16)–C(23)
N(1)–C(9)
N(1)–C(12)
N(2)–C(12)
1.537(3)
1.518(3)
1.515(3)
1.383(3)
1.381(3)
1.383(4)
1.362(4)
1.370(4)
1.386(3)
1.391(3)
1.378(3)
1.378(3)
1.405(3)
1.390(3)
1.386(3)
1.379(3)
N(2)–C(15)
N(3)–C(17)
N(3)–C(18)
N(3)–C(20)
N(4)–C(20)
N(4)–C(23)
O(1)–C(9)
O(2)–C(15)
O(3)–C(17)
O(4)–C(23)
S(1)–C(12)
S(2)–C(20)
O(1)–Hb
1.383(3)
1.388(3)
1.482(3)
1.381(3)
1.372(3)
1.385(3)
1.272(3)
1.301(3)
1.296(3)
1.278(3)
1.661(3)
1.665(2)
1.346(6)
1.104(5)
1.209(5)
1.470(7)
longer than the average C᎐O bond distance (1.223(3) Å) in 3. In
᎐
addition, evidence for partial C᎐C double bonding in the detba
᎐
O(2)–Ha
O(3)–Hb
O(4)–Ha
rings in 6 is given by the average C–C distance of 1.388(6) Å
which is ca. 0.07 Å shorter than the average of C(11)–C(12) and
C(11)–C(16) in 3 (1.462(4) Å). The structure of 6 exhibits no
noteworthy intermolecular contacts.
C(2)–C(3)–C(4)
C(2)–C(7)–C(6)
C(3)–C(2)–C(1)
C(3)–C(2)–C(7)
C(4)–C(5)–C(6)
C(5)–C(4)–C(3)
C(5)–C(6)–C(7)
C(7)–C(2)–C(1)
C(8)–C(1)–C(2)
C(8)–C(9)–N(1)
C(8)–C(15)–N(2)
C(9)–C(8)–C(1)
C(12)–N(1)–C(9)
C(12)–N(2)–C(15)
C(15)–C(8)–C(1)
C(15)–C(8)–C(9)
C(16)–C(1)–C(2)
C(16)–C(1)–C(8)
C(16)–C(17)–N(3)
C(17)–C(16)–C(1)
120.7(2)
121.1(2)
120.45(19)
117.7(2)
118.9(2)
121.2(3)
120.5(2)
121.72(19)
114.63(16)
119.2(2)
120.7(2)
121.5(2)
123.4(2)
122.6(2)
120.19(19)
117.8(2)
115.58(18)
111.54(17)
120.46(19)
123.63(18)
C(17)–C(16)–C(23)
C(20)–N(3)–C(17)
C(20)–N(4)–C(23)
C(23)–C(16)–C(1)
N(1)–C(12)–N(2)
N(1)–C(12)–S(1)
N(2)–C(12)–S(1)
N(3)–C(20)–S(2)
N(4)–C(20)–N(3)
N(4)–C(20)–S(2)
N(4)–C(23)–C(16)
O(1)–C(9)–C(8)
O(1)–C(9)–N(1)
O(2)–C(15)–C(8)
O(2)–C(15)–N(2)
O(3)–C(17)–C(16)
O(3)–C(17)–N(3)
O(4)–C(23)–C(16)
O(4)–C(23)–N(4)
117.6(2)
122.26(19)
123.22(18)
118.27(19)
115.4(2)
121.87(18)
122.76(19)
121.50(18)
116.12(19)
122.36(16)
119.3(2)
124.4(2)
116.46(19)
124.1(2)
115.2(2)
123.9(2)
Evidence that the other Michael adducts also adopt mixed
keto–enol structures in the solid state is provided by the infra-
red spectra of 2 and 5–10 which show ν(CO) absorptions in the
Ϫ1
region 1618–1607 cm . As expected, the Knoevenagel products
3 and 4 show keto stretching bands at higher energies. The
absence of clear signals for the enolic protons in the NMR
spectra of 2 and 5–10 is consistent with excessive broadening
due to rapid exchange in solution. Indeed, very broad signals
in the region ca. 9–10 ppm can be observed in some of these
spectra. Complex splitting of the proton NMR ethyl signals for
2 and 5–10 is also in keeping with the presence of mixed
keto–enol structures in solution.
The structure of 3 is especially interesting because the
molecular dimensions can be correlated with NLO properties.
Although 3 itself has not been subjected to NLO investigations,
115.7(2)
123.9(2)
116.81(19)
n
its -N( Bu)2 analogue (3-Bu) is known to possess marked
molecular quadratic NLO properties, i.e. a large first hyper-
6b
polarisability, β. This observation, together with dipole
6b
products are stabilised by extended conjugation. It is likely that
the pronounced difference in reactivity between dmabza and
the other arylaldehydes arises primarily from electronic factors.
It has been shown that the Lewis acidity of Knoevenagel
products, and hence reactivity towards Michael addition,
increases either as electron-withdrawing substituents are added
moment measurements, is indicative of a significant contri-
bution by the charge-separated (zwitterionic) resonance form
to the ground state structure (Fig. 3). Recent theoretical
and experimental studies with donor–acceptor polyenes have
clarified understanding of structure–property relationships for
molecular NLO properties. Hence, a relationship between β and
the “bond length alternation” (BLA, defined as the difference
11
or as the molecule becomes more planar. The strongly basic 4-
NMe substituent in 3 will stabilise the vinyl group and render it
less susceptible to nucleophilic attack. By contrast, the electron-
between the average “C–C” and “C᎐C” bond distances) has
᎐
13
2
been established. If the neutral form prevails in the ground
J. Chem. Soc., Perkin Trans. 1, 1999, 2483–2488 2485

View Article Online
Experimental
Materials and procedures
4
-Ferrocenylbenzaldehyde was prepared according to a pub-
17
lished procedure and all other reagents were obtained com-
mercially and used as supplied. Products were dried overnight
at room temperature in a vacuum desiccator (CaSO ) prior to
4
characterisation.
Fig. 3 Limiting canonical resonance forms for compound 3.
Physical measurements
state, then 0 < BLA/Å < 0.11, whilst predominance of the
zwitterionic form leads to Ϫ0.11 > BLA/Å > 0. Equal mixing
of the two limiting resonance forms gives BLA and β values of
Proton NMR spectra were recorded on a Varian Gemini 200
spectrometer and all shifts are referenced to TMS. Chemical
shifts are given in ppm; J values are given in Hz; cm = complex
multiplet. Any fine splitting of pyridyl or phenyl ring AAЈBBЈ
patterns is ignored and the signals are reported as simple
doublets. Elemental analyses were performed by the Micro-
analytical Laboratory, University of Manchester. Melting
points were recorded by using a Gallenkamp melting point
apparatus. IR spectra were obtained as KBr discs with an ATI
Mattson Genesis Series FTIR instrument, and UV-visible
spectra were recorded using a Hewlett-Packard 8452A diode
array spectrophotometer. Mass spectra were recorded by using
ϩ/Ϫ electrospray on a Micromass Platform spectrometer (cone
0
[
,
whilst
±(0.05 ± 0.01) Å].
Our crystallographic study confirms that extensive polarisa-
β is maximised at intermediate BLA values
6b
tion occurs in the ground state of 3. The bond distance
2
C(1)–C(7) is ca. 0.05 Å shorter than a typical C(Ar)–C(sp )
distance, whilst C(7)–C(11) is ca. 0.04 Å longer than a typical
2
2
15
C(sp )᎐C(sp ) distance in a C᎐C–C᎐O fragment. Further-
more, the phenyl ring shows a partial quinoidal structure, the
average of C(5)–C(6) and C(2)–C(3) being ca. 0.05 Å shorter
than the average of the other four intra-ring bonds. However,
comparison of the bond distances within the detba ring with
those in 6 provides no evidence for the adoption of an aromatic
structure. The difference C(1)–C(7) Ϫ C(7)–C(11) for 3 is ca.
voltage 80 V) (for 2 and 5–10) or using NH chemical ionisation
on a VG Trio 2000 spectrometer (for 3 and 4).
3
0
.05 Å, and if taken as a BLA value then this structure is
optimised with regard to a NLO response. This is only an
approximation because 3 contains only a single methine unit,
but nevertheless the structural data are clearly consistent with
the pronounced NLO properties of 3-Bu. By contrast, 11 has a
BLA of ca. Ϫ0.01 Å, indicating a slight predominance of the
charge-separated form in the ground state. The marked differ-
ence in the extent of ground state charge-separation between 3
and 11 can be ascribed to more effective donor–acceptor π-
conjugation via the trans-buta-1,4-dienyl unit when compared
to the phenylene bridge in 3.
Syntheses
4
-Pyridylbis(1,3-diethyl-2-thio-4,6-dioxohexahydro-5-pyrimi-
dyl)methane 2. To a stirring solution of pyridine-4-carbalde-
hyde (pyca, 69 mg, 0.644 mmol) in ethanol (50 mL) was added a
solution of 1,3-diethyl-2-thiobarbituric acid (detba, 513 mg,
13
2
.56 mmol) in ethanol (45 mL). A white precipitate began to
form within minutes. After stirring at room temperature for 8 h,
the precipitate was filtered off, washed with ethanol and dried.
The white solid obtained was found to contain residual ethanol
by proton NMR, so was reprecipitated from DMF–water: yield
2
85 mg, 88%; δ (CD SOCD ) 8.69 (2 H, d, J 6.6, C H N), 7.75
H 3 3 5 4
(
4
2 H, d, J 6.8, C H N), 6.51 (1 H, s, CH), 4.56–4.38 (8 H, cm,
5
4
Ϫ1
CH -Me), 1.20 (12 H, t, J 6.8, 4CH -Me). ν(C᎐O) 1607 cm .
2
2
Mp 245–248 (decomp.) ЊC. Found: C, 52.49; H, 5.60; N,
13.78; S, 12.74. Calc. for C H N O S ؒ0.75H O: C, 52.52; H,
22 27 5 4 2 2
ϩ
5.71; N, 13.92; S, 12.75%. m/z: 489 (M ).
As expected for a highly conjugated structure, the phenyl
and detba rings in 3 are almost perfectly coplanar, with torsion
angles as follows: C(2)–C(1)–C(7)–C(11) = 1.4Њ, C(6)–C(1)–
C(7)–C(11) = 178.9Њ,C(1)–C(7)–C(11)–C(16) = 2.9Њ,C(1)–C(7)–
C(11)–C(12) = Ϫ179.2Њ. There is evidence for opening out of
the bond angles in the methine bridge to accommodate this
planar structure, with the angle C(11)–C(7)–C(1) of 138.5(2)Њ
being particularly large for a trigonal centre. Although the
molecular structure of 3 is clearly highly favourable for
quadratic NLO properties, the adoption of a centrosymmetric
space group precludes the observation of any macroscopic NLO
1,3-Diethyl-5-[4-(dimethylamino)benzylidene]-2-thiobarbituric
acid 3. This was prepared in a similar manner to 2 by using 4-
(dimethylamino)benzaldehyde (dmabza, 96 mg, 0.643 mmol)
in place of pyca, and detba (258 mg, 1.29 mmol) in ethanol
(30 mL). The solution turned orange immediately and a red
precipitate began to form within minutes. A red solid was
obtained: yield 185 mg, 87%; δ
), 8.42 (1 H, s, CH), 6.71 (2 H, d, J 9.4, C
q, J 6.9, CH -Me), 4.58 (2 H, q, J 7.0, CH -Me), 3.17 (6 H,
s, NMe ), 1.33 (3 H, t, J 6.9, CH -Me), 1.31 (3 H, t, J 7.0,
CH -Me). λmax(MeCN)/nm (ε/dm mol cm ) 244 (15 100),
(CDCl ) 8.42 (2 H, d, J 9.3,
3
H
C
H
6
H
6 4
), 4.59 (2 H,
4
2
2
2
2
16
3
Ϫ1
Ϫ1
effects with this particular crystalline form. As with 6, the
structure of 3 exhibits no interesting intermolecular contacts.
2
Ϫ1
284 (12 200), 314 (11 600), 492 (87 100). ν(C᎐O) 1653 cm .
Mp 204–208 ЊC (lit. 212–214 ЊC). Found: C, 61.51; H, 6.32;
9
N, 12.57; S, 9.80. Calc. for C H N O S: C, 61.61; H, 6.39;
N, 12.68; S, 9.67%. m/z: 332 (M ).
1
7
21
3
2
Conclusions
ϩ
We have shown that novel arylbis(1,3-diethyl-2-thiobarbitur-
5
-yl)methanes can be readily prepared from various arylalde-
1,3-Diethyl-5-[3-phenylprop-2-enylidene]-2-thiobarbituric acid
4. This was prepared in a similar manner to 3 by using cinna-
maldehyde (100 mg, 0.757 mmol) in place of dmabza, and
detba (303 mg, 1.51 mmol). The reaction turned yellow within
minutes, and precipitation commenced after ca. 1.5 h. A bright
yellow solid was obtained: yield 82 mg, 34%; δ (CDCl ) 8.63
3
hydes in high yields. The sp methine unit in these compounds
renders them unlikely to exhibit marked NLO properties, but
they can be expected to possess interesting host–guest recogni-
tion behaviour and biological activity. X-Ray crystallography
provides clear evidence for extensive polarisation in the ground
state molecular structure of 1,3-diethyl-5-[4-(dimethylamino)-
benzylidene]-2-thiobarbituric acid (3), consistent with the pro-
H
3
(1 H, dd, J 12.1, 15.3, CH), 8.22 (1 H, d, J 12.1, CH), 7.72–7.68
(2 H, C H ), 7.51–7.43 (4 H, CH and C H ), 4.55 (4 H, cm,
6
5
6
5
n
3
nounced molecular NLO properties of the analogous -N( Bu)2
compound.
2CH -Me), 1.31 (6 H, cm, 2CH -Me). λmax(MeCN)/nm (ε/dm
mol cm ) 240 (13 900), 266 (9800), 398 (56 300). ν(C᎐O) 1665
2
Ϫ1
2
Ϫ1
᎐
2
486
J. Chem. Soc., Perkin Trans. 1, 1999, 2483–2488

View Article Online
Ϫ1
Ϫ1
cm . Mp 179–180 ЊC. Found: C, 65.16; H, 5.78; N, 8.85;
ν(C᎐O) 1619 cm . Mp 147–151 ЊC (decomp.). Found: C, 59.04;
S, 10.44. Calc. for C H N O S: C, 64.94; H, 5.77; N, 8.91;
S, 10.20%. m/z: 315 (M ).
H, 5.48; N, 8.50; S, 9.70. Calc. for C H FeN O S : C, 58.93;
H, 5.39; N, 8.33; S, 9.53%. m/z: 671 (M ).
17
ϩ
18
2
2
33 36
ϩ
4
4 2
4
-Methoxyphenylbis(1,3-diethyl-2-thio-4,6-dioxohexahydro-5-
4-Dimethylaminophenylbis(1,3-diethyl-2-thio-4,6-dioxohexa-
hydro-5-pyrimidyl)methane 10. A solution of 3 (100 mg, 0.302
mmol) and detba (181 mg, 0.904 mmol) in ethanol (40 mL) was
heated at reflux for 8 h. The reaction solution was allowed to
cool to room temperature overnight, and the precipitate was
filtered off, washed with ethanol to remove detba, then CHCl3
to remove unreacted 3 and dried: yield 31 mg, 19%; δ (CD -
pyrimidyl)methane 5. This was prepared in an identical manner
to 2 by using 4-methoxybenzaldehyde (83 mg, 0.644 mmol) in
place of pyca. The reaction turned yellow within minutes, and
precipitation commenced after ca. 5 h. A bright yellow solid
was obtained: yield 216 mg, 65%; δ (CDCl ) 7.04 (2 H, d, J 8.9,
H
3
C H ), 6.85 (2 H, d, J 8.9, C H ), 5.63 (1 H, s, CH), 4.72–4.54
6
4
6
4
H
3
(
4
4
8 H, cm, 4CH -Me), 3.81 (3 H, s, OMe), 1.42–1.27 (12 H, cm,
CH -Me). λ (MeCN)/nm (ε/dm mol cm ) 288 (26 900),
00 (16 200). ν(C᎐O) 1618 cm . Mp 133–136 ЊC. Found:
C, 55.80; H, 5.95; N, 10.89; S, 12.24. Calc. for C H N O S :
C, 55.58; H, 5.83; N, 10.80; S, 12.36%. m/z: 519 (M ). Concen-
tration of the filtrate produced a further 64 mg of pure product
total yield 84%).
SOCD ) 7.48 (2 H, d, J 8.4, C H ), 7.16 (2 H, d, J 8.3, C H ),
2
3 6 4 6 4
3
Ϫ1
Ϫ1
2
max
6.32 (1 H, s, CH), 4.55–4.38 (8 H, cm, 4CH -Me), 1.19 (12 H,
2
Ϫ1
Ϫ1
᎐
t, J 6.6, 4CH -Me). ν(C᎐O) 1613(1638sh) cm . Mp 158–161 ЊC
᎐
2
2
4
30
4
5 2
(decomp.). Found: C, 56.16; H, 6.45; N, 13.05; S, 12.12. Calc.
for C H N O S : C, 56.47; H, 6.26; N, 13.17; S, 12.06%.
ϩ
2
5
33
5
4 2
Ϫ
m/z: 529 (M ).
(
X-Ray structural determinations
Crystals were obtained from CHCl solutions, those of 3 by
slow evaporation and those of 6 by inward diffusion of diethyl
ether vapour. An orange crystal of 3 of approximate dimen-
sions 0.4 × 0.3 × 0.3 mm and a pale yellow crystal of 6 with
dimensions 0.6 × 0.2 × 0.2 mm were chosen for diffraction
studies.
Phenylbis(1,3-diethyl-2-thio-4,6-dioxohexahydro-5-pyrimidyl)-
3
methane 6. This was prepared in an identical manner to 2 by
using benzaldehyde (68 mg, 0.641 mmol) in place of pyca.
Precipitation commenced after ca. 2.5 h and a white solid was
3
,4,5
obtained: yield 132 mg, 42%; δ (CDCl ) 7.34–7.26 (3 H, H ),
H
3
2,6
7
4
2
5
.14 (2 H, d, J 8.1, H ), 5.69 (1 H, s, CH), 4.73–4.54 (8 H, cm,
CH -Me), 1.39 (6 H, t, J 7.0, 2CH -Me), 1.30 (6 H, t, J 7.0,
2
2
Data collection details are as follows: for 3, data were
collected on a Siemens SMART CCD area-detector diffrac-
tometer. For three settings of ꢀ, narrow data frames were
collected for 0.3Њ increments in ω to afford a sphere of data. At
the end of data collection the first 50 frames were recollected to
confirm that crystal decay had not taken place. An empirical
absorption correction was applied by using multiple measure-
ments of equivalent reflections, and the data frames were inte-
Ϫ1
CH -Me). ν(C᎐O) 1617 cm . Mp 174–176 ЊC. Found: C,
2
6.70; H, 5.77; N, 11.39; S, 13.12. Calc. for C H N O S :
23
28
ϩ
4
4 2
C, 56.54; H, 5.78; N, 11.47; S, 13.12%. m/z: 489 (M ). Con-
centration of the filtrate produced a further 150 mg of pure
product (total yield 90%).
4
-Cyanophenylbis(1,3-diethyl-2-thio-4,6-dioxohexahydro-5-
pyrimidyl)methane 7. This was prepared in an identical manner
to 2 by using 4-cyanobenzaldehyde (84 mg, 0.641 mmol) in
place of pyca. Precipitation commenced after ca. 2 h and a
white solid was obtained: yield 175 mg, 53%; δ (CDCl ) 7.63
18
grated using SAINT. For 6, data were collected on a Nonius
Kappa CCD area-detector diffractometer at the window of a
rotating anode FR591 generator (50 kV, 20 mA) and controlled
by the Collect software package. Images of 2Њ thickness and
10 s exposure were taken in a 360Њ ꢀ scan, followed by five
shorter ω scans, with a detector-to-crystal distance of 30 mm
19
H
3
(
2 H, d, J 8.4, C H ), 7.28 (2 H, d, J 8.1, C H ), 5.67 (1 H, s,
6
4
6
4
CH), 4.71–4.52 (8 H, cm, 4CH -Me), 1.41–1.26 (12 H, cm,
2
Ϫ1
4
5
CH -Me). ν(C᎐O) 1618 cm . Mp 195–196 ЊC. Found: C,
20
2
(θ offsets between 3.3Њ and 9.95Њ) and processed by Denzo to
6.59; H, 5.13; N, 13.55; S, 12.49. Calc. for C H N O S :
2
4
27
5
4
2
give 99.4% coverage of the unique data set. Data were corrected
for absorption by using the empirical method employed in
ϩ
C, 56.12; H, 5.30; N, 13.63; S, 12.49%. m/z: 513 (M ). Concen-
tration of the filtrate produced a further 41 mg of pure product
21
22
Sortav from within the MaXus suite of programs.
(
total yield 66%).
The structure of 3 was solved by direct methods and refined
2
by full-matrix least-squares on all F0 data using Siemens
4
-Nitrophenylbis(1,3-diethyl-2-thio-4,6-dioxohexahydro-5-
18
SHELXTL 5.03. The same approach was used for 6, but using
pyrimidyl)methane 8. This was prepared in an identical manner
to 2 by using 4-nitrobenzaldehyde (97 mg, 0.642 mmol) in place
of pyca. Precipitation commenced after ca. 2 h and a white
solid was obtained: yield 176 mg, 51%; δ (CDCl ) 8.19 (2 H,
23
24
SHELXS-97 and SHELXL-97. In both cases, all non-
hydrogen atoms were refined anisotropically with hydrogen
atoms included in idealised positions (C–H distance = 0.97 Å)
with thermal parameters riding on those of the parent atom.
Representations of 3 and 6 are given in Fig. 1 and 2. Crystal-
lographic data and refinement details are presented in Table 1,
and selected bond distances and angles in Table 2. Additional
material available from the CCDC comprises final atomic
fractional coordinates, thermal parameters, and complete tables
of bond lengths and angles. CCDC reference number 207/253.
See http://www.rsc.org/suppdata/p1/1999/2483 for crystallo-
graphic files in .cif format.
H
3
d, J 8.9, C H ), 7.33 (2 H, d, J 9.0, C H ), 5.70 (1 H, s, CH),
6
4
6
4
4
1
1
.75–4.56 (8 H, cm, 4CH -Me), 1.39 (6 H, t, J 7.0, 2CH -Me),
2
2
Ϫ1
.30 (6 H, t, J 7.0, 2CH -Me). ν(C᎐O) 1618 cm . Mp 198–
2
99 ЊC. Found: C, 51.89; H, 5.20; N, 12.98; S, 11.86. Calc. for
C H N O S : C, 51.77; H, 5.10; N, 13.12; S, 12.02%. m/z: 534
2
3
ϩ
27
5
6 2
(
M ). Concentration of the filtrate produced a further 44 mg
of pure product (total yield 64%).
4
-Ferrocenylphenylbis(1,3-diethyl-2-thio-4,6-dioxohexahydro-
5
-pyrimidyl)methane 9. This was prepared in an identical
manner to 3 by using 4-ferrocenylbenzaldehyde (93 mg, 0.321
mmol) in place of dmabza. The reaction turned brown followed
by olive green within 1 h, but no precipitation occurred. After
References
1
L. F. Tietze and U. Beifuss, in Comprehensive Organic Synthesis:
Vol. 2, ed. B. M. Trost, Pergamon, Oxford, 1991.
8
h the solution was concentrated to ca. 10 mL and upon
2 K. Popov-Pergal and M. Pergal, Collect. Czech. Chem. Commun.,
1992, 57, 1153 and refs. therein.
standing overnight at room temperature, the product crystal-
lized out as a brown solid: yield 188 mg, 87%; δ (CDCl ) 7.42
3
T. Koike, M. Takashige, E. Kimura, H. Fujioka and M. Shiro,
Chem. Eur. J., 1996, 2, 617 and refs. therein.
T. Chin, Z. Gao, I. Lelouche, Y. K. Shin, A. Purandare, S. Knapp
and S. S. Isied, J. Am. Chem. Soc., 1997, 119, 12849.
H
3
(
2 H, d, J 8.4, C H ), 7.04 (2 H, d, J 8.1, C H ), 5.65 (1 H, s,
6
4
6
4
4
CH), 4.72–4.56 (10 H, cm, 4CH -Me and C H ), 4.32 (2 H, s,
C H ), 4.04 (5 H, s, C H ), 1.43–1.29 (12 H, cm, 4CH -Me).
λmax(CH Cl )/nm (ε/dm mol cm ) 294 (38 100), 434 (630).
2
5
4
5
4
5
3
5
2
5 S. R. Marder, D. N. Beratan and L.-T. Cheng, Science, 1991, 252,
Ϫ1
Ϫ1
2
2
103.
J. Chem. Soc., Perkin Trans. 1, 1999, 2483–2488
2487

View Article Online
15 Average bond distances taken from: CRC Handbook of Chemistry
and Physics, ed. D. R. Lide, CRC Press, Boca Raton, 75th edn,
1994.
16 Nonlinear Optical Properties of Organic Molecules and Crystals,
eds. D. S. Chemla and J. Zyss, Academic Press, Orlando, 1987,
vols. 1 and 2.
6
7
(a) S. R. Marder, L.-T. Cheng, B. G. Tiemann, A. C. Friedli,
M. Blanchard-Desce, J. W. Perry and J. Skindhøj, Science, 1994,
2
63, 511; (b) M. Blanchard-Desce, V. Alain, P. V. Bedworth,
S. R. Marder, A. Fort, C. Runser, M. Barzoukas, S. Lebus,
R. Wortmann, Chem. Eur. J., 1997, 3, 1091.
(a) B. J. Coe, M. C. Chamberlain, J. P. Essex-Lopresti, S. Gaines,
J. C. Jeffery, S. Houbrechts and A. Persoons, Inorg. Chem., 1997, 36,
17 B. J. Coe, C. J. Jones, J. A. McCleverty, D. Bloor and G. Cross,
J. Organomet. Chem., 1994, 464, 225.
3
284; (b) B. J. Coe, J. P. Essex-Lopresti, J. A. Harris, S. Houbrechts
and A. Persoons, Chem. Commun., 1997, 1645; (c) B. J. Coe, J. A.
Harris, L. J. Harrington, J. C. Jeffery, L. H. Rees, S. Houbrechts and
A. Persoons, Inorg. Chem., 1998, 37, 3391.
M. Conrad and H. Reinbach, Chem. Ber., 1901, 34, 1339.
L. G. S. Brooker, G. H. Keyes, R. H. Sprague, R. H. VanDyke,
E. VanLare, G. VanZandt, F. L. White, H. W. J. Cressman and
S. G. Dent, J. Am. Chem. Soc., 1951, 73, 5332.
18 SHELXTL 5.03 program system, Siemens Analytical X-Ray
Instruments, Madison, WI, 1995.
19 Collect: Data collection software, R. Hooft, Nonius B. V., 1998.
20 Z. Otwinowski and W. Minor, Methods in Enzymology, Vol. 276:
Macromolecular Crystallography, Part A, eds. C. W. Carter, Jr. and
R. M. Sweet, Academic Press, London, 1997, p. 307.
21 (a) R. H. Blessing, Acta. Crystallogr., Sect. A, 1995, 51, 33; (b) R. H.
Blessing, J. Appl. Crystallogr., 1997, 30, 421.
22 S. Mackay, C. J. Gilmore, C. Edwards, M. Tremayne, N. Stewart,
K. Shankland, MaXus: a computer program for the solution and
refinement of crystal structures from diffraction data, University of
Glasgow.
8
9
1
1
1
0 K. Kondo, S. Ochiai, K. Takemoto, Y. Kai, N. Kasai and
K. Yoshida, Chem. Phys. Lett., 1992, 188, 282.
1 F. J. Kunz, P. Margaretha and O. E. Polansky, Chimia, 1970, 24,
1
65.
2 Recent examples: (a) L. Prasad and M. R. Taylor, Acta Crystallogr.,
Sect. C, 1983, 39, 1686; (b) M. Millan, C. F. Conde, A. Conde
and R. Marquez, Acta Crystallogr., Sect. C, 1985, 41, 274;
23 G. M. Sheldrick, Acta Crystallogr., Sect. A, 1990, 46, 467.
24 G. M. Sheldrick, SHELXL 97, Program for crystal structure
refinement, University of Gottingen, 1997.
(
c) H. Takayanagi, S. Munemura, M. Goto, H. Ogura and M. Onda,
J. Pharm. Soc. Jpn., 1986, 106, 867.
1
3 G. Bourhill, J.-L. Brédas, L.-T. Cheng, S. R. Marder, F. Meyers,
J. W. Perry and B. G. Tiemann, J. Am. Chem. Soc., 1994, 116, 2619.
4 V. Bertolasi, P. Gilli, V. Ferretti and G. Gilli, J. Chem. Soc., Perkin
Trans. 2, 1997, 945.
1
Paper 9/04015C
2
488
J. Chem. Soc., Perkin Trans. 1, 1999, 2483–2488