4-(4-methoxyphenylamino)-3-phenylazo-3-penten-2-one

Article abstract of DOI:10.1107/S0108270101004851

The title compound, C₁₈H₁₉N₃O₂, was obtained by an azocoupling reaction with enaminones and is composed of a planar azoenamine skeleton which forms a six-membered ring through a symmetrical intramolecular hydrogen bond. The compound was found to exist as an equilibrium mixture of major hydrazoimino and minor azoenamine tautomers. Quantification of the relative contribution of the tautomeric forms is obscured by the existence of the hydrogen bond. Comparison of the results with those obtained for a similar structure revealed a substantial effect on the tautomeric equilibria of the nature of the substituent bonded to the amine nitrogen.

Full text of DOI:10.1107/S0108270101004851

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
ciple, exist in tautomeric forms (Ia±c). Previous studies have
shown that the proportion of individual tautomers depends
sensitively on the nature of substituents R ±R ; recent results
1
4
1
3
15
ISSN 0108-2701
from C and N NMR spectroscopy have revealed that the
title derivative [(II); R = R = Me, R = Ph, R = 4-
1
2
3
4
methoxyphenyl] exists in CDCl solution predominantly in the
3
4
-(4-Methoxyphenylamino)-3-phenyl-
hydrazo form, (Ib), with a small amount of the azo form, (Ia)
(
Mach a cÏ ek et al., 2001). To con®rm the NMR results and, at
the same time, to establish the structural details, a single-
crystal X-ray analysis of (II) was undertaken.
azo-3-penten-2-one
a
b
c
Æ
Viktor Kettmann, * Jan Lokaj, Petr Simunek and
Vladim Âõ r Mach a cÏ ek
c
a
Faculty of Pharmacy, Comenius University, Odbojarov 10, Bratislava 83232, Slovak
b
Republic, Faculty of Chemical Technology, Slovak Technical University, Radlin-
c
skeho 9, Bratislava 81237, Slovak Republic, and Department of Organic Chemistry,
University of Pardubice, Pardubice 53218, Czech Republic
Correspondence e-mail: kettmann@fpharm.uniba.sk
Received 31 January 2001
Accepted 19 March 2001
The title compound, C H N O , was obtained by an azo-
2
1
8
19
3
coupling reaction with enaminones and is composed of a
planar azoenamine skeleton which forms a six-membered ring
through a symmetrical intramolecular hydrogen bond. The
compound was found to exist as an equilibrium mixture of
major hydrazoimino and minor azoenamine tautomers.
Quanti®cation of the relative contribution of the tautomeric
forms is obscured by the existence of the hydrogen bond.
Comparison of the results with those obtained for a similar
structure revealed a substantial effect on the tautomeric
equilibria of the nature of the substituent bonded to the amine
nitrogen.
The molecular structure together with the atom-numbering
scheme is shown in Fig. 1. As can be seen, the azoenamine
grouping (atoms N7, N8, C9, C13 and N15) in the central part
Ê
of the molecule adopts a planar [r.m.s. deviation 0.014 (2) A]
chelate-like form and is completed to a six-membered ring
through an intramolecular hydrogen bond between atoms N7
and N15. The hydrogen bond is symmetrical: the H15 atom
Comment
N-Substituted aminoethylene derivatives having carbonyl
function(s) in the ꢀ-position ± known as enaminones ± have
been extensively investigated because of their interesting
structural characteristics, such as distinct geometric forms and
tautomerism (Eberlin et al., 1990). They can also be viewed as
push±pull ethylenes, a class of reactive and versatile
compounds presenting an unusually low rotational barrier
around the C C double bond with an absorption in the near-
ultraviolet and visible regions due to the delocalization of ꢁ
electrons (Wennerbeck, 1973). Therefore, such compounds
have found widespread applications in pharmaceutical and
medicinal chemistry, e.g. as prodrugs of primary amines or
intermediates in the preparation of antiulcer and antibacterial
drugs (Naringrekar & Stella, 1990; Vishnu, 1980), as well as in
the chemical industry (organic dyes and agrochemicals). The
structural and hence the physicochemical variability of en-
aminones is even increased upon introduction of an azo group
to the ꢀ-position of the ethylenic bond; such azo-coupling
products from enaminones and diazonium ions may, in prin-
Figure 1
A view of the title molecule showing the labelling of the non-H atoms.
Displacement ellipsoids are shown at the 35% probability level and H
atoms are drawn as small circles of arbitrary radii. Dashed lines indicate
the symmetrical intramolecular hydrogen bond.
ꢀ
Acta Cryst. (2001). C57, 737±739
# 2001 International Union of Crystallography
Printed in Great Britain ± all rights reserved 737

organic compounds
was found in the difference Fourier synthesis midway between
N7 and N15, and was freely re®ned. The details of this
hydrogen bond are: N7Á Á ÁH15 1.35 (3), N15Á Á ÁH15 1.45 (3),
ethyl 2-[(E)-5-chloro-2-hydroxy-4-nitrophenylazo]-3-(E)-am-
ino-2-butenoate [(III); Rodrigues et al., 1996]. The two
compounds, (II) and (III), differ mainly in that (III) contains a
Ê
ꢁ
N7Á Á ÁN15 2.479 (3) A and N7Á Á ÁH15Á Á ÁN15 125 (2) . Of the
substituents, the acetyl group and the phenyl ring at N7 are
approximately coplanar with the plane of the central six-
primary amine (R = H) instead of the 4-methoxyphenylamine
4
group. The principal characteristics of the two structures are
the same with the exception that in (III), the H atom remains
bonded to the amine nitrogen, i.e. the compound exists
predominantly as the azoenamine tautomer, (Ia). Thus, based
on the results obtained from (II) and (III), it may be
concluded that the position of the tautomeric equilibria is a
sensitive function of the substituents bonded to the terminal
azo and amine N atoms (R and R ).
ꢁ
membered ring, the dihedral angles being 3.5 (2) and 7.3 (2) ,
respectively. By contrast, the 4-methoxyphenyl group bonded
ꢁ
to the aminic nitrogen (N15) is rotated by 67.7 (1) from the
central molecular plane. Thus, the planarity of the molecule as
a whole is perturbed by the 4-methoxyphenyl group.
As noted above, the main purpose of the present work was
to identify the tautomer in which the title compound, (II),
exists in the solid state [or the percentage of the possible forms
3
4
As the only hydrogen-bond donor of the molecule is
involved in the intramolecular hydrogen bond, the inter-
molecular packing is governed by van der Waals interactions.
(
Ia±c) if it exists as an equilibrium mixture]. This can be
performed crystallographically by determining the bond
orders from the bond-length±bond-order curves proposed by
Burke-Laing & Laing (1976). The C9ÐC13 and C13ÐN15
Ê
bond lengths of 1.473 (4) and 1.271 (3) A (Table 1), respec-
2
2
tively, are close to the values reported for a pure Csp ÐCsp
Experimental
Ê
Compound (II) was prepared by the following procedure: aniline
single bond [1.487 (5) A; Shmueli et al., 1973] and a pure
Ê
N double bond (1.27 A; Burke-Laing & Laing, 1976).
These results are consistent with those obtained from NMR
(0.93 g, 10 mmol) in tetra¯uoroboric acid (10 ml of ca 30% HBF
was diazotized by adding a solution of sodium nitrite (0.69 g,
0 mmol) in water (5 ml). After several minutes, sodium tetra-
uoroborate (1 g, 9 mmol) was added, the suspension of benzene-
4
)
C
1
spectroscopy (Mach a cÏ ek et al., 2001), which have indicated
that (II) exists in CDCl solution as a 90:10 mixture of (Ib):(Ia)
¯
3
diazonium tetra¯uoroborate formed was mixed, and the precipitated
solid collected by suction and thoroughly pressed on a small sintered-
glass ®lter. The almost dry product was added portion-wise to a
solution of 4-(4-methoxyphenylamino)-3-penten-2-one (2.26 g,
11 mmol) in diisopropyl ether (15 ml). The mixture was stirred at
273 K for 2 h, whereupon the solid was collected by suction, resus-
pended in a chloroform±ethyl acetate mixture (1:1, ca 10 ml) and
transferred onto a silica-gel column. The product was eluted by the
same solvent mixture. The fraction containing the product along with
the unreacted enaminone was subjected to vacuum distillation to
remove the solvent, and the residue was repeatedly triturated with
hexane. The less hexane-soluble residue was again submitted to
chromatography on a silica-gel column with a chloroform±ethyl
acetate mixture (1:1). Finally, the product was recrystallized from
cyclohexane (m.p. 411±413 K).
[
with no contribution of (Ic)]. On the other hand, the N7ÐN8
Ê
and N8ÐC9 bond distances [1.316 (3) and 1.309 (3) A,
respectively] are both intermediate between single and double
bonds (bond orders ca 1.4 and 1.7), assuming values of 1.41,
Ê
1
.23, 1.45 and 1.27 A for NÐN, N N, CÐN and C N bonds,
respectively (Burke-Laing & Laing, 1976). Obviously, if only
forms (Ia) and (Ib) contribute to the electronic structure of
the molecule, then there is a discrepancy in the indications
concerning the position of the imine-enamine and azohy-
drazone tautomerisms. The discrepancy does not seem to be
caused by some contribution of the enol form, (Ic), as indi-
cated by a pure single-bond and a pure double-bond character
of the C9ÐC10 and C10ÐO11 bonds, respectively (Table 1).
Instead, the inconsistency most likely originates from the
existence of the symmetrical hydrogen bond [i.e. the H atom is
not bonded to N7 as required by formula (Ib)] which should
promote an accumulation of electron density on N7 and
subsequently its transfer to the adjacent phenyl ring. Indeed,
some degree of conjugation of the hydrazone moiety (atoms
N7, N8 and C9) with the phenyl ring (which should result in
the lowering and increasing of the C9ÐN8 and N8ÐN7 bond
orders, respectively) is clearly seen in (i) the coplanarity of the
hydrazone group with the phenyl ring, (ii) a partial double-
bond character of C1ÐN7, and (iii) a non-equivalency of the
phenyl-ring CÐC bonds (Table 1).
Crystal data
C
18
H
19
N
3
O
2
m
D measured by ¯otation in
bromoform/cyclohexane
r
M = 309.36
Monoclinic, P2
1
Ê
/c
Mo Kꢂ radiation
Cell parameters from 15
re¯ections
a = 11.525 (5) A
Ê
b = 14.465 (6) A
Ê
c = 9.761 (3) A
ꢁ
ꢃ = 7±18
ꢁ
� 1
ꢀ
= 92.82 (4)
V = 1625.3 (11) A
ꢄ = 0.08 mm
T = 293 (2) K
Ê
3
Z = 4
Plate, yellow
0.30 Â 0.25 Â 0.10 mm
�
3
D
D
x
= 1.264 Mg m
= 1.27 (1) Mg m
� 3
m
Another purpose of this work was to compare the present
results with those of similar structures in order to explore the
effects of substituents R ±R bonded to the azoenamine
skeleton on the position of the tautomeric equilibria in the
solid state. However, a search of the Cambridge Structural
Database (Allen & Kennard, 1993) for structures containing
the azoenamine substructure revealed only one compound,
Data collection
Syntex P2
ꢃ/2ꢃ scans
1
diffractometer
h = � 13 ! 0
1
4
k = 0 ! 17
3054 measured re¯ections
l = � 11 ! 11
2
1
890 independent re¯ections
319 re¯ections with I > 2ꢅ(I)
2 standard re¯ections
every 98 re¯ections
intensity decay: 4%
R
int = 0.049
ꢁ
ꢃ
max = 25.1
ꢀ
738 Viktor Kettmann et al.
18
C H
N O
19 3 2
Acta Cryst. (2001). C57, 737±739

organic compounds
Re®nement
Data collection: Syntex P21 Diffractometer Software (Syntex,
2
1
1
973); cell re®nement: Syntex P2 Diffractometer Software; data
Re®nement on F
R(F) = 0.070
H atoms treated by a mixture of
independent and constrained
re®nement
reduction: XP21 (Pavel cÏ õÂ k, 1987); program(s) used to solve structure:
SHELXS97 (Sheldrick, 1997); program(s) used to re®ne structure:
SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII
2
wR(F ) = 0.139
S = 0.93
2
2
2
w = 1/[ꢅ (F
where P = (F
(Á/ꢅ)max = 0.002
Áꢆmax = 0.11 e A
Áꢆmin = � 0.12 e AÊ
o
) + (0.0433P) ]
+ 2F )/3
o c
2 2
2
2
890 re¯ections
15 parameters
(Johnson, 1976); software used to prepare material for publication:
SHELXL97.
Ê
� 3
� 3
This work was ®nancially supported by the Grant Agency of
the Slovak Republic (project No. 1/8216/01).
Table 1
Selected geometric parameters (A, ).
Ê
ꢁ
C1ÐC6
C1ÐN7
C1ÐC2
C2ÐC3
C3ÐC4
C4ÐC5
C5ÐC6
1.362 (4)
1.394 (3)
1.403 (4)
1.392 (4)
1.372 (4)
1.362 (4)
1.412 (4)
N7ÐN8
N8ÐC9
1.316 (3)
1.309 (3)
1.473 (4)
1.493 (4)
1.204 (3)
1.271 (3)
1.433 (3)
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GD1141). Services for accessing these data are
described at the back of the journal.
C9ÐC13
C9ÐC10
C10ÐO11
C13ÐN15
N15ÐC16
References
C6ÐC1ÐN7
C6ÐC1ÐC2
N7ÐC1ÐC2
N8ÐN7ÐC1
C9ÐN8ÐN7
N8ÐC9ÐC13
N8ÐC9ÐC10
124.2 (3)
119.9 (3)
115.9 (3)
118.3 (2)
117.8 (2)
125.4 (3)
110.9 (3)
C13ÐC9ÐC10
O11ÐC10ÐC9
N15ÐC13ÐC9
N15ÐC13ÐC14
C9ÐC13ÐC14
C13ÐN15ÐC16
123.4 (3)
123.0 (3)
116.9 (2)
124.0 (3)
119.1 (3)
120.5 (2)
Allen, F. H. & Kennard, O. (1993). Chem. Des. Autom. News, 8, 1, 31±37.
Burke-Laing, M. & Laing, M. (1976). Acta Cryst. B32, 3216±3224.
Eberlin, M. N., Takahata, Y. & Kascheres, C. (1990). J. Mol. Struct.
(Theochem), 207, 143±156.
Johnson, C. K. (1976). ORTEPII. Report ORNL-3794. Oak Ridge National
Laboratory, Tennessee, USA.
Æ
Mach a cÏ ek, V., Ly cÏ ka, A., Simunek, P. & Weidlich, T. (2001). J. Magn. Reson.
Submitted.
C6ÐC1ÐN7ÐN8
C1ÐN7ÐN8ÐC9
N7ÐN8ÐC9ÐC13
N7ÐN8ÐC9ÐC10
N8ÐC9ÐC13ÐN15
� 3.4 (4)
178.5 (3)
� 3.9 (4)
� 178.8 (2)
1.1 (4)
N8ÐC9ÐC13ÐC14
C10ÐC9ÐC13ÐC14
C9ÐC13ÐN15ÐC16
C13ÐN15ÐC16ÐC17
C20ÐC19ÐO22ÐC23
179.5 (3)
� 6.2 (4)
178.6 (2)
72.1 (4)
Naringrekar, V. H. & Stella, V. J. (1990). J. Pharm. Sci. 79, 138±146.
Pavel cÏ õÂ k, F. (1987). XP21. Comenius University, Slovakia.
Rodrigues, B. L., Gambardella, M. T. P., Figueiredo, L. J. O. & Kascheres, C.
(
1996). Acta Cryst. C52, 705±707.
164.9 (3)
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of G oÈ tt-
ingen, Germany.
Shmueli, U., Shanan-Atidi, H., Horwitz, H. & Shvo, Y. (1973). J. Chem. Soc.
Perkin Trans. 2, pp. 657±662.
Syntex (1973). Syntex P2 Diffractometer Software. Syntex Analytical X-ray
1
Instruments Inc., Cupertino, California, USA.
Vishnu, J. R. (1980). Arch. Pharm. (Weinheim), 313, 471±476.
Wennerbeck, I. (1973). Acta Chem. Scand. 27, 258±270.
H atoms were treated as riding, with Uiso set to 1.2 (1.5 for the
methyl H atoms) times Ueq of the parent atom, except for the H atom
H15 (linking N15 and N7), which was fully re®ned with respect to
positional and Uiso parameters.
ꢀ
Acta Cryst. (2001). C57, 737±739
Viktor Kettmann et al.
18 19 3
C H N O
2
739