Insights on the synthesis and organisational phenomena of twisted pyrazine-pyridine hybrids

Article abstract of DOI:10.1039/b107751a

Pyrazine-pyridine hybrids containing two different oligopyridyl chains, 2,3-disubstituted onto the pyrazine ring nucleus are prepared from appropriate mixed α-diketone precursors. The latter were obtained by epoxidation of the enols of corresponding 1,2-disubstituted ethanones. The structures of the pyrazine derivatives were investigated by detailed proton NMR spectroscopic and X-ray crystallographic methods. These indicated a twisting of the oligopyridyl chains about one another to result in a pre-double helical topology. This phenomenon occurred up to two pyridin-2,6-diyl groupings from the pyrazine ring and is accompanied by edge-on-face stacking of spatially proximate pyridyl rings. Parallel stacking of pyrazine and weak C-H···N acid interactions are significant in their crystal lattices and may also figure in their metallosupramolecular self-assembly behaviour patterns.

Full text of DOI:10.1039/b107751a

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Insights on the synthesis and organisational phenomena of twisted
pyrazine–pyridine hybrids
Fenton Heirtzler,*† Markus Neuburger and Klaus Kulike
1
Departement Chemie, Universität Basel, CH-4056 Basel, Switzerland
Received (in Cambridge, UK) 29th August 2001, Accepted 28th January 2002
First published as an Advance Article on the web 25th February 2002
Pyrazine–pyridine hybrids containing two different oligopyridyl chains, 2,3-disubstituted onto the pyrazine ring
nucleus are prepared from appropriate mixed α-diketone precursors. The latter were obtained by epoxidation of the
enols of corresponding 1,2-disubstituted ethanones. The structures of the pyrazine derivatives were investigated by
detailed proton NMR spectroscopic and X-ray crystallographic methods. These indicated a twisting of the
oligopyridyl chains about one another to result in a pre-double helical topology. This phenomenon occurred up to
two pyridin-2,6-diyl groupings from the pyrazine ring and is accompanied by edge-on-face stacking of spatially
proximate pyridyl rings. Parallel stacking of pyrazine and weak C–H ؒ ؒ ؒ N acid interactions are significant in their
crystal lattices and may also figure in their metallosupramolecular self-assembly behaviour patterns.
Our pyrazine–pyridine hybrids self-assemble to form dimeric
Introduction
complexes with appropriate labile metal centres. By studying
the organisational patterns of the native ligands in the solid
state, particularly those involving ligand geometry/electro-
negativity, π-stacking effects and the weak acidity of sp2-
hybridised C–H bonds,13 inferences concerning this behaviour
may be possible. Of further interest is the topology of extended
pyrazine–pyridine hybrids. Vicinal positioning of two 2,2Ј-
bipyridyl moieties such as in 2 inclines them to twist about one
another, both in solution and the solid state.8f In view of the
current interest in helically self-organising molecules,14 some of
which are also based on electron-deficient aza-aromatics, it is
valid to assess 1 for evidence of extended double helicity.
Finally, methods are needed for the preparation of functionally
elaborate pyrazine–pyridine hybrids. These will provide the
molecular scaffolding upon which light-harvesting systems can
be based.15
The physical properties of pyrazine derivatives—e.g. dipole
moments, multipole-based or π-stacking interactions, con-
jugative effects and base strength—differ from those of other
electron-deficient aza-aromatics.1 This forms the basis of their
eventual use in light-harvesting systems,2 conducting materials3
and polymers,4 liquid crystalline substances,5 dyes 6 and metallo-
organics.7 Our work is in the synthesis of 2,3-disubstituted
pyrazine–pyridine hybrids, e.g. compound 1, and exploration
of their supramolecular chemistry.8 Unlike the plethora of
different types of “pure” oligopyridine-type compounds,
for which mature synthetic methodologies are available,9 the
preparation of such pyrazine–pyridine hybrids requires the
development of original methods,10,1b and this has arguably11
held back their development. Prior to our work, a total of three
pyrazine–pyridine hybrids having relatively simple and regular
structures were known.12
We have recently issued a preliminary communication on the
preparation of such unsymmetrical pyrazine–pyridine hybrids,
e.g. 3a via α-diketones like 4a.8b We now address the out-
standing synthetic work in this context, and consider their
topological and self-organisational properties.
Results and discussion
Claisen–Rubottom ꢀ-diketone synthesis
Esters 6 were prepared by basic methanolysis of the corre-
sponding carbonitriles, and those compounds were in turn
prepared by a modified Reissert–Henze reaction16 of the oligo-
pyridine N-oxides as previously described.8b Treatment of
6-methylpyridine derivatives 5 with 2 equiv. LDA, followed by
addition of 6 afforded the condensation products 7 (Scheme 1).
For 7d–f, and h, this amide base reacted directly with the ester
to form side-products that were tentatively identified on the
basis of their 1H NMR spectra as N,N-diisopropyl amides. The
formation of these materials can be rationalised on the basis
of the increased electrophillic reactivity of the α-position of
2-pyridyl derivatives.17 The chromatographic separation of
those diisopropyl amides was only possible in the synthesis
of 7h. For 7d–f, the more sterically hindered base, lithium
tetramethylpiperidide (LTMP) precluded formation of these
side-products. As was previously alluded to,8b the stability of all
† Correspondence address: Chemical Laboratory, School of Physical
Sciences, University of Kent, Canterbury, UK CT2 7NH. E-mail:
frh@ukc.ac.uk; Fax: ϩ44 (0)1227 82 77 24; Tel: ϩ44 (0)1227 82 70 41.
DOI: 10.1039/b107751a
J. Chem. Soc., Perkin Trans. 1, 2002, 809–820
This journal is © The Royal Society of Chemistry 2002
809

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Scheme 1 Claisen–Rubottom synthesis of α-diketones 4 and thus pyrazines 3. MCPBA: m-chloroperbenzoic acid.
of these condensation products varied approximately inversely
with their solubilities.
Integration of the proton NMR spectra indicated the enolimine
forms to predominate by 66–86%. This finding is in accord
with hydrogen-bonding reinforced tautomeric effects.19 It also
agrees with the proposed destabilisation of ketimine tautomers
observed for highly electronegative aryl groups that are
attached to the carbonyl carbon.19 An X-ray crystal structure
determination carried out on the bis-condensation product 7c
supports these findings. The tautomer of 7c observed in the
solid state is also the majority form in solution.20
The crucial part of the pyrazine synthesis was the trans-
formation of the condensation products 7 into the α-diketones
4. Treatment of 7a–f under Rubottom conditions21—i.e. 1
equivalent of m-chloroperbenzoic acid (MCPBA) in a biphasic
aqueous sodium bicarbonate–dichloromethane system—
afforded the dihydroxyolefins 8. These were expeditiously
oxidised to 4 using a dichloromethane solution of one equiv-
alent iodine. Clean formation of α-diketone 4g could only
be accomplished by treatment of 7g with two equivalents of
m-CPBA. Ethanones 7h,i did not form the corresponding
α-diketones under diverse conditions.
The condensation products occur as dynamic mixtures of
two tautomers. Their 1H NMR spectra display two closely over-
lapping sets of resonances and their proton-decoupled 13C
NMR spectra generally show double sets of lines. By com-
parison of the magnitudes of the enolic and ketonic shifts at
δH = 6.82–7.12 and δC = 198.2–202.6, to values from the liter-
ature,18 they could be identified as the ketimine and enolimine
forms 7K and 7E; enaminone tautomers 7M were not observed.
This synthetic sequence deserves comment. On one hand, it
circumvents the low reactivity and scrambling22 of Umpolung
reagents prepared from pyridine-2-carbaldehyde derivatives.23
Formation of α-diketones by direct α-oxygenation of ketones24
or their silyl enol ethers,25 as well as α-halogenation26 are all
well-established procedures that did not function for the bis-
pyridyl-substituted condensation products 7. Other peracids,
e.g. peracetic acid and magnesium monoperoxyphthalate
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Scheme 2 Reaction pathways for treatment of condensation products with meta-chloroperbenzoic acid. BV = Baeyer–Villiger-type product;
Ar = m-ClC6H4.
(mmpp) were likewise unsuitable. The most likely mechanistic
explanation for the formation of 8 would involve epoxidation
of the enolimine tautomer 7E to form intermediate 9 (Scheme 2,
Path A). This must occur significantly more rapidly than the
competing Baeyer–Villiger oxidation of the ketimine tautomer,
since none of the ester products to be expected from that reac-
tion27 were detected in the crude reaction mixtures (Path B). An
alternate mechanism would involve the formation of a pyridine
N-oxide derivative 10 from the ketimine tautomer, and its sub-
sequent rearrangement28 to the α-hydroxyketone ester 11 (Path
C). This would, however require that N-oxidation occur only on
the pyridyl ring adjacent to the oxidisable site.
The unsymmetrical α-diketones could all be isolated as
crystalline solids, although the stability of the methylpyridyl
bipyridyl compounds 4e, f dictated that they be further reacted
in a synthetically pure state. Like the parent 1,2-di-2Ј-pyridyl-
ethan-1,2-dione,29 upon prolonged exposure to light in the solid
state, they decompose to green-coloured materials. The 1H
NMR spectra of 4 were assigned through various combinations
of COSY, NOESY, selective proton decoupling, DIFNOE and
long-range HETCOR experiments. Generally, δH of the pyridyl,
2,2Ј-bipyridyl (bpy) and 2,2Ј:6Ј,2Љ-terpyridyl (terpy) ring sys-
tems occurred at values that were unique and characteristic of
a given position in a fragment, e.g. H-5 of C5H4N appeared
at δH 7.47–7.48, 7.21–7.24 and 7.30–7.32 respectively. This
provides an additional level of certainty in their assignments,
as well as indicating the absence of interactions across the
diketone bridge. In the cases of 4a, c and d, complete assign-
ment of 13C NMR spectra were also carried out. All α-diketone
spectra exhibited the expected numbers of signals, displaying
two carbonyl carbon resonances.
carried out. Of special note was the observation of four-bond
coupling JCH = ca. 4 Hz between 2-C and H-5 on each of the
4
mono-substituted pyridyl groups of the bpy-terpy-substituted
3d. This phenomena permitted the establishment of the con-
nectivity through each of those oligopyridyl groups, and thus
through the entire molecule. In the remaining compounds the
correct numbers of signals as expected from their structures
were observed.
Twisting in solution and solid state
A prominent feature of the 1H NMR spectra of compounds 3 is
the pronounced upfield shifting of H-3 on the second pyridyl
ring separated from pyrazine. In those containing the bipyri-
dyl(pyridyl)pyrazine scaffolding (3a, e and f ), this shift is at
δH 7.22–7.38. On one hand, this is more than 1.1 ppm upfield
from calculated values. On the other hand, it contributes to the
conspicuous reversal of expected shift magnitude patterns, i.e.
usually δH-4 < δH-3.
30 Since the 1H shift magnitudes from the bpy
portions of all three of these compounds closely resemble each
other, their conformations must also be similar. Also, the 5-
methylpyridyl derivative 3e displays non-overlapping absorp-
tions on that solitary ring. Thus, it was possible to observe
NOE effects between H-3 (vide infra) and H-3, H-6 of
C5H3N(CH3). We therefore attribute this upfield shifting to
non-bonding interactions involving H-3.
The shift magnitudes of positions on the 6-methylpyridyl
ring of 3f closely match those on the unsymmetrical model
compound 3g. In 3g, through-space effects are expected to be
considerably less pronounced. After correlating these findings
back to 3a, e and f, one can therefore deduce that in 3a, the
C5H4N rings of bpy and solitary pyridyl groups respectively
form the base and top of a “T-like” edge-on-interaction, in
particular one in which H-3 experiences magnetic anisotropic
effects. Interestingly, the strength of the interactions among 3a,
e and f is greater than that originally observed for compound 2
(H-3 at δH 8.02).8f
The final two steps in the reaction sequence were concept-
ually straightforward. After condensation of the diketones
with an appropriate molar equivalent of ethylenediamine, the
intermediate dihydropyrazines (not shown) were conveniently
oxidised to pyrazines 3 by treatment with chloranil in xylene
under reflux.
The solution-state structures of the pyrazine derivatives 3
were thoroughly analysed using 1H NMR spectroscopy (Fig. 1).
In contrast to the situation for the α-diketones, these shift
patterns occurred with partial signal overlap. Nevertheless,
although complete assignment of the JHH coupling patterns
was sometimes not possible, the shift magnitudes could be
accurately localised through a combination of 2D and proton–
proton decoupling techniques (vide supra). In the cases of com-
pounds 3d, f, complete assignment of the 13C NMR spectra was
While compounds 3a and e exhibit similar melting points,
isomeric 3f could not be isolated as a solid. In spite of repeated
column chromatography, merely an oil was obtained that,
according to thin layer chromatographic and NMR spectro-
scopic analysis, was nonetheless pure. We considered two
rationalisations for this phenomena: the presence of multiple
conformational equilibria or severe (intermolecular) packing
defects that inhibited crystallisation. The absence of both strong
temperature-dependence in the 1H NMR spectra of 3f and
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Fig. 1 Proton NMR overlay of pyrazine–pyridine hybrids 3a–d.
spatial NOE effects between the 6-C methyl group and posi-
tions in the bpy ring system in that compound imply the latter.
The remaining three pyrazine derivatives 3b–d showed
similar 1H NMR spectroscopic phenomena. Dipyrazine 3c
exhibited a shift assigned to H-5 at δH 7.15–7.22, or ca. 0.8 ppm
upfield from calculated values. The number of signals in the
spectrum of that same compound (also in its 13C NMR)
bespeaks of a symmetrical meso or C2 structure. In the terpy-
substituted derivatives 3b and d display analogous phenomena,
since H-3 on the second C5H3N ring removed from pyrazinyl
appears upfield by ca. 0.75 ppm. The bpy-terpy derivative 2d
additionally gives rise to shielding phenomena associated with
twisting of the bpy flank, H-3 appearing at δH 8.06, or ca. 1 ppm
upfield from expected values. The orthogonal shielding
arrangement does not extend to the terminal terpy pyridyl ring,
since all these protons absorb at frequencies close to expected
values.
In order to compare the solution-state structures with the
solid state, crystal structure determinations were carried out.
For compound 3a, the inter-annular angle between the pyr-
azinyl and the bpy C5H3N ring is ca. 28Њ, whilst the solitary
C5H4N ring is correspondingly rotated by 42Њ (Fig. 2A). The
angle between the two C5H4N rings is 69Њ. Thus, H-3 does,
indeed undergo an edge-on interaction. The crystal structure of
3c is similar, but less pronounced (Fig. 3A)—the planes of the
C5H4N and adjacent C5H3N rings are rotated 44Њ and 31Њ with
respect to the pyrazinyl ring. The angle between the mean
planes of both of these rings is 54Њ. The same compound
furthermore possesses an overall meso-stereochemistry, since
the twist of each pyridyl pyrazine fragment is in the opposite
direction.
For 3d, a double-helical geometry is observed up to the
second pyridyl ring removed from pyrazine (Fig. 4A). Beyond
this point, the preferred transoid arrangement characteristic of
2,2Ј-oligopyridyl ring systems31 prevails, and the terminal ring
of terpy is directed away from the approximate helical axis. Two
independent but geometrically similar molecules of 3d occur
within the unit cell. The average angles by which the bpy C5H3N
and terpy C5H3N rings are deflected from the plane of the
adjoining pyrazinyl ring are 46 and 30Њ respectively.
Both π-electronic and torsional steric/C᎐N dipole effects are
᎐
possible explanations for the preference of the pyrazine deriva-
tives for twisted geometries.32 According to current theory,33
interaction between two orthogonal electron-poor aromatic
systems can be stabilising. Furthermore, a hydrogen donor–π-
electron acceptor interaction is quantified by the distance of H
from the π-electron system and the deflection, α, of the attached
C–H bond from the individual atoms.13 Thus, for d defined as
the distance between H and πC, the centre of the π-electron
system, d < 3.05 Å is crucial, since this value corresponds to the
sum of the van der Waals radius of hydrogen plus the Pauling
one-half thickness of benzene. Additionally, the condition
150Њ < α < 180Њ must be met, since only then is the C–H bond
deflected towards the p-orbitals of the π-electron system. These
calculated parameters are summarised for 3a, c and g in Table 1;
data for compound 28f are included for comparison.
For all compounds except 3d, the approach of H-3 to πC
is closer than to any ring atoms. However, it is only for 3a
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Fig. 2 Depiction of intra- and intermolecular interactions for 3a in the crystal lattice. A. intramolecular twisting; B. pyrazine stacking; C. dimeric
C–H ؒ ؒ ؒ N interactions; D. pyridine stacking.
Fig. 3 Solid-state structure and lattice interactions in 3c. A. Meso-twisted conformation; B. catenating C–H ؒ ؒ ؒ N interactions; C. columnar
stacking of intermeshed pyrazinyl rings; D. cross-linking of sheets of columns through C–H ؒ ؒ ؒ N interactions.
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Table 1 Geometrical parameters of pyrazine–pyridine hybrids related to C–H ؒ ؒ ؒ π interactions
3d
3d
3dЈc
Bpy C5H4N–
Tpy C5H3N
3dЈc
Tpy C5H3N–
Bpy C5H3N
Bpy C5H4N–
Tpy C5H3N
Tpy C5H3N–
Bpy C5H3N
3a
3c
2
dπC(–H-3)/Å
α/Њa
2.87
158
3.16
134
3.78
141
3.16
134
3.23
138
3.01
131
3.23
143
dЈ(N-1)/Åb
dЈ(C-2)/Åb
dЈ(C-3)/Åb
dЈ(C-4)/Åb
dЈ(C-5)/Åb
dЈ(C-6)/Åb
3.14
3.09
3.16
3.23
3.24
3.18
3.53
3.31
3.23
3.36
3.57
3.61
3.76
3.73
4.02
4.29
4.29
4.02
3.85
3.28
3.14
3.31
3.61
3.70
3.57
3.39
3.38
3.48
3.60
3.64
3.49
3.22
3.05
3.13
3.38
3.64
3.53
3.43
3.42
3.49
3.67
3.57
a α = 3-C–H-3–πC. b dЈ = Separation from H-3 to indicated position on the orthogonal ring. c Two independent molecules in unit cell.
Fig. 4 Solid-state structure of terpyridyl bipyridyl 3d. A. overall twisting of Bpy ring systems around terpy; B. weak parallel interpyridine stacking.
that both of the aforementioned criteria are met. The tentative
conclusion is that although C–H ؒ ؒ ؒ π interactions may
reinforce the orthogonal interactions of the pyridyl groups,
they do not per se induce them. The double-helical twisting
in these pyrazine-pyridine hybrids is therefore principally of
steric–dipole origin.
laps with 4-C of its neighbour, and distances of 3.69 Å are
thereby observed. Overlaps of a similar magnitude between 2-C
and the adjacent H-4 are also observed.
The crystal lattice of 3c displays progressively interwoven
degrees of organisation. Molecules are interconnected through
dimeric C–H ؒ ؒ ؒ N interactions between H-6 and N of the
C5H4N rings (2.76 Å), forming achiral ribbons (Fig. 3B).
Although this effect has been observed in other nitrogen-
containing arenes,34 to our knowledge, it has not yet been
documented from positions directly adjacent to pyridine nitro-
gen. Neighbouring ribbons are interdigitated through offset
stacking of the pyrazine rings, which thus form columns
running through the lattice (Fig. 3C). The centroid-to-centroid
distances between the pyrazine rings are 3.92 and 3.79 Å.
Judged from these derived values, the offset between the rings is
15.54Њ, or 0.53 Å. A similar feature occurs in the crystal struc-
ture of pyrazine itself.35 Additional C–H ؒ ؒ ؒ N interactions
existing between N of C5H4N and H-5 of the pyrazine ring
(2.79 Å) may also contribute towards stabilisation of this array.
The interdigitated ribbons together form pleated sheets, and
these sheets are interconnected by contacts between H-4 of
bpy and N-1 of pyrazine of 2.61 Å (Fig. 3D). This is below the
sum of the concerned van der Waals radii36 and the vector
represented by the 4-C–H-4 bond deviates by ca. 36Њ from the
mean plane of the pyrazine ring. Therefore, this relation-
ship meets the criteria outlined for a C–H ؒ ؒ ؒ N hydrogen
bonding interaction.37 Furthermore, comparison between these
Lattice and stacking interactions
It was also of interest to determine whether the lattice inter-
actions in 3a had any bearing on the poor crystallinity of
derivative 3f or the low solubility and high melting point of 3c.
In 3a, two sorts of intermolecular parallel stacking effects are
apparent (Fig. 2B). In the first, pyrazine rings are aligned in
antiparallel columns. This overlap is, however not perfect and
adjacent pyrazine rings are slipped offset by 32Њ in an alter-
nating fashion. Adjacent molecules are also enantiomerically
related with respect to their sense of helical twisting. This
results in different separations between the centroids of the
pyrazine rings, 3.67 and 4.55 Å for the ring faces bearing the
bpy and pyridyl substituents respectively. Stepping back yet
again, one sees that neighbouring stacks are aligned through
dimeric C–H ؒ ؒ ؒ N hydrogen bond donor–acceptor inter-
actions (2.67 Å) between H-4 of bpy and N-1 of pyrazine
(Fig. 2C). The second parallel stacking effect involves the
C5H4N rings of bpy, which exhibit a slipped anti-parallel
alignment (Fig. 2D). The centroid of one ring efficiently over-
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interactions in compounds 3a and 3c shows that for the former
a dimeric supramolecular synthon results, whereas for the latter
a catenated supramolecular synthon results.
In contrast, the lattice of 3d is distinguished by the absence
of inter-pyrazine stacking interactions. The only parallel
π-stacking evident involves the first and third pyridyl rings
of the terpy ring system in one of the two molecules present
in the asymmetric cell (Fig. 4B). This occurs through parallel
(not anti-parallel) orientation of the two concerned rings. The
overlapping terpy systems are also inclined 19Њ to one other.
Pyrazine 3a
Pyrazine 3a has been previously reported:8b νmax/cmϪ1 (KBr)
3055 (w, Ar C–H), 1581 (s, Ar C᎐C), 1560 (s, Ar C᎐C), 837 (m,
Ar C–H), 781 (s, Ar C–H); δC(CDCl3, 75 MHz) 158.14 (C),
155.67 (C), 155.52 (C), 154.63 (C), 152.86 (C), 151.99 (C),
148.96 (CH), 148.90 (CH), 142.62 (CH), 137.85 (CH), 136.39
(CH), 136.30 (CH), 124.06 (CH), 123.86 (CH), 123.64 (CH),
122.77 (CH), 120.75 (CH), 120.48 (CH); λmax(MeCN)/nm = 237
(log ε/dm3 molϪ1 cmϪ1 4.30 sh), 248 (4.32), 282 (4.43).
᎐
᎐
3b
Analogous to the synthesis of 3a, 4b afforded 3b in 48% yield
after recrystallisation (heptane–CH2Cl2) as colourless rhombo-
hedral crystals. νmax/cmϪ1 (KBr) 3060 (m, Ar C–H), 1579 (s, Ar
Conclusions
A convergent synthesis of unsymmetrical pyrazine–pyridine
hybrids using mixed α-diketones as immediate precursors has
been presented. A novel epoxidation reaction of keto–enol
tautomeric ethanones affords those diketones.
C᎐C), 1564 (s, Ar C᎐C), 810 (m, Ar C–H), 783 (s, Ar C–H), 744
᎐
᎐
(m, Ar C–H); δH(CDCl3, 300 MHz) 8.71 (s, 2H, H-5, H-6), 8.68
(br d, J 4.8, 1H, H-6ЉЉ), 8.55–8.59 (m, 2H, H-3Ј,5Ј, H-3ЉЉ), 8.42
(dt, J 1.3, 4.9, 1H, H-6Љ), 8.35 (dd, J 1.0, 7.8, 1H, H-5ٞ), 8.16
(dd, J 1.0, 7.7, 1H, H-5Ј,3Ј), 8.00 (t, J 7.8, 1H, H-4Ј), 7.79–7.87
(m, 3H, H-3Љ, H-4Љ, H-4ЉЉ), 7.66 (t, J 7.8, 1H, H-4ٞ), 7.32 (ddd,
J 1.2, 4.8, 7.5, 1H, H-5ЉЉ), 7.28 (br d, J 7.1, 1H, H-3ٞ), 7.20
(ddd, J 2.5; 4.9, 7.2, 1H, H-5Љ); δC(CDCl3, 75 MHz) 158.10
(C), 156.08(C), 155.41(C), 155.06 (C), 154.78 (C), 154.59 (C),
152.86 (C), 151.91 (C), 149.07 (CH), 148.92 (CH), 142.61 (CH),
142.58 (CH), 137.77 (CH), 137.37 (CH), 136.82 (CH), 136.34
(CH), 124.02 (CH), 123.83 (CH), 123.72 (CH), 122.81 (CH),
121.06 (CH), 120.89 (CH), 120.62 (CH), 120.51 (CH); m/z 388
([M]ϩ, 100%), 387 ([M Ϫ H]ϩ, 100), 336 ([M Ϫ NCCN]ϩ, 4),
334 ([M Ϫ C2H2N2]ϩ, 3), 233 ([M Ϫ C10H7N2]ϩ, 7), 194 ([M Ϫ
C10H7N2 Ϫ C2HN]ϩ, 12). Found: C, 74.16; H, 4.27; N, 21.54.
Calc. for C24H16N6: C, 74.21; H, 4.15; N, 21.64%.
On the basis of solid- and solution-state studies, the
pyrazine–pyridine hybrids can be described as preferentially
twisted, pre-double helically shaped compounds occurring on a
relatively small scale molecular format. Proton NMR spectro-
scopic evidence indicates that the second pyridyl ring out from
pyrazine orthogonally juts into the first pyridyl ring of the other
group attached to pyrazine. Uniformly, H-3 on that second ring
is shifted upfield by δ 1.0 ppm, indicating that in solution, the
average twisting is comparable for all compounds. The same
geometry can also enable C–H ؒ ؒ ؒ π stacking interactions—
at least in the solid state—however, the extent to which this
is possible is subordinate to steric effects manifested by the
pendant transoid oligopyridyl substituents.
Additionally, the solid-state structures illustrated several
supramolecular synthons: offset stacking of pyrazine rings,
weak C–H ؒ ؒ ؒ N hydrogen bonding and trans-annular dis-
tortion of oligopyridyl ring systems from transoid-coplanar
conformity. Pyrazine stacking appears to be favoured in those
hybrids having relatively high pyrazine content. It is also a
central self-organising feature of the dicopper(I) complex
of 3a.8d Thus, the manifestation of these features in their
metallo–organic supramolecular complexes is a topic of future
and ongoing interest.
3c
Analogous to the synthesis of 3a, 4c afforded 3c in 44%
yield after reaction with 2 equiv. each of ethylenediamine and
chloranil. Recrystallisation (CH2Cl2–Me2CHOH) afforded
colourless small blocks for combustion analysis. Mp > 400 ЊC;
νmax/cmϪ1 (KBr) 3060 (w, Ar C–H), 1587 (m, Ar C᎐C), 1577 (s,
᎐
Ar C᎐C), 1566 (s, Ar C᎐C), 831 (m, Ar C–H), 802 (s, Ar C–H),
᎐
᎐
779 (s, Ar C–H), 744 (s, Ar C–H); δH(CDCl3, 300 MHz) 8.69 (s,
4H, H-5, H-6), 8.37 (br d, J 4.8, 2H, H-6Љ), 8.02 (dd, J 1.0, 7.7,
2H, H-3Ј), 7.79–7.81 (m, 2H, H-3Љ, H-4Љ), 7.66 (t, J 7.9, 1H,
H-4Ј), 7.15–7.22 (m, 2H, H-5Ј, H-5Љ); δC(CDCl3, 75 MHz)
158.02 (C, 1C), 155.20 (C, 1C), 154.11 (C, 1C), 152.70 (C,
1C), 151.81 (C, 1C), 148.77 (CH, 1C), 142.61 (CH, 2C), 137.37
(CH, 1C), 136.41 (CH, 1C), 124.05 (CH, 1C), 123.74 (CH,
1C), 122.84 (CH, 1C), 120.20 (CH, 1C); m/z 466 ([M]ϩ, 100%),
414 ([M Ϫ NCCN]ϩ, 4), 412 ([M Ϫ HNCCNH]ϩ, 3), 388 ([M Ϫ
C5H4N]ϩ, 94), 335 ([M Ϫ C5H4N Ϫ C2HN2]ϩ, 7), 233 ([M/2]ϩ,
33), 232 ([M/2 Ϫ H]ϩ, 53). Found: C, 70.56; H, 4.10; N, 23.58.
Calc. for C28H18N8ؒ½H2O: C, 70.73; H, 4.03; N, 23.56%.
Experimental
Infrared spectra were recorded on Mattson Genesis Fourier-
transform spectrophotometers with samples in compressed
KBr discs. Proton and carbon NMR spectra were recorded
on Varian Gemini (300, 75 MHz), Bruker DRX 500 (500,
125 MHz) or JEOL GX (270, 67.5 MHz) spectrometers. δH and
δC values are referenced to Me4Si and CHCl3, respectively.
J values are given in Hz. Unless otherwise indicated, δC assign-
ments refer to single, magnetically equivalent carbon atoms.
For the ethanone derivatives, key resonances in their NMR
spectra are reported for identification of the ketimine and
enolimine tautomers and to establish the positions of their
keto–enol tautomeric equilibria. Unless indicated otherwise, all
mass spectra were recorded as electron-impact (EI) spectra
(including relative intensities) on VG 70–250, Kratos MS-902
or Finnigan 8430 spectrometers at 70 eV. Column chroma-
tography was performed with silica gel (70–230 mesh, Fluka)
or aluminium oxide/activity III (Fluka). Anhydrous diethyl
ether, tetrahydrofuran, 1,2-dimethoxyethane and toluene were
freshly distilled from sodium–benzophenone ketal under
dry nitrogen gas. Dry dichloromethane was freshly distilled
from P4O10. Diisopropylamine and tetramethylpiperidine were
distilled from CaH2 and stored over activated 5 Å molecular
sieves. Methanol was distilled from iodine-activated magnesium
turnings and stored over freshly-activated 5 Å molecular
sieves. Unless indicated, all other chemicals were commercially
available and used as received.
3d
Analogous to the synthesis of 3a, 4d afforded 3d in 67% yield
after recrystallisation (heptane–CHCl3) in the form of colour-
less rhombohedral crystals. νmax/cmϪ1 (KBr) 3055 (w, Ar C–H),
1576 (m, Ar C᎐C), 1566 (s, Ar C᎐C), 821 (m, Ar C–H), 780 (s,
᎐
᎐
Ar C–H); δH(CDCl3, 500 MHz) 8.74 (s, 2H, H-5, H-6), 8.65 (br
d, J ca. 4.8, 1H, H-6ЉЉ), 8.50–8.52 (m, 3H, H-5Љ, H-3ЉЉ, H-6Љٞ),
8.32 (dd, J 1.1, 7.8, 1H, H-5Ј), 8.30 (dd, J 1.1, 7.8, 1H, H-5ٞ),
8.060 (dd, J 1.2, 7.7, 1H, H-3Љ), 8.054 (dd, J ca. 1.2, 7.7, 1H,
H-3Ј), 8.01 (t, J 7.6, 1H, H-4Љ), 7.99 (t, J 7.6, 1H, H-4Ј), 7.80 (br
t, J 7.7, 1H, H-4ЉЉ), 7.62 (t, J 7.8, 1H, H-4ЉЉ), 7.45–7.48 (m, 3H,
H-3ЉЉ, H-3Љٞ, H-4Љٞ), 7.27–7.30 (m, 1H, H-5ЉЉ), 7.11–7.13 (m,
1H, H-5Љٞ); δC(CDCl3, 125 MHz, 280 K) 156.45 (C, 1C, 6Љ-C),
156.38 (C, 1C, 6Ј-C), 155.89 (C, 1C, 2ЉЉ-C), 155.43 (C, 1C,
2Љٞ-C), 154.97, 154.92, 154.91, 154.65 (C, 4C, 2Ј-C, 2Љ-C, 2Љ-C,
6ٞ-C), 152.49 (C, 1C, 3-C), 152.44 (C, 1C, 2-C), 149.00 (6ЉЉ-C),
J. Chem. Soc., Perkin Trans. 1, 2002, 809–820
815

View Article Online
148.79 (6Љٞ-C), 142.59 (CH, 1C, 5/6-C), 142.58 (6/5-C), 137.67
(CH, 1C, 4Љ-C), 137.57 (CH, 1C, 4ٞ-C), 137.54 (CH, 1C, 4Ј-C),
136.75 (CH, 1C, 4ЉЉ-C), 136.57 (CH, 1C, 4Љٞ-C), 123.68 (CH,
2C, 3Љ-C, 3Ј-C), 123.63 (CH, 1C, C-5Љٞ), 123.61 (CH, 2C,
3Ј,3Љ-C, 5ЉЉ-C), 120.96 (CH, 1C, 5Ј,3ЉЉ-C), 120.84 (CH, 1C,
5ٞ-C), 120.70 (CH, 1C, 3ٞ,3Љٞ-C), 120.64 (CH, 1C, 3ЉЉ,3ٞ-C),
120.28 (CH, 1C, 3ЉЉ,5Ј-C ), 120.19 (CH, 1C, 5Љ-C); m/z 465
([M]ϩ, 100%), 464 ([M Ϫ H]ϩ, 85), 387 [M Ϫ C5H4N]ϩ, 12),
310 ([M Ϫ C10H7N2]ϩ, 9), 233 ([M Ϫ C15H11N3]ϩ, 20), 155
([C10H7N2]ϩ, 6). Found: C, 73.54; H, 4.23; N, 20.82. Calc. for
C29H19N7Oؒ½ H2O: C, 73.40; H, 4.25; N, 20.66%.
121.12 (CH, 1C), 24.21 (CH3, 1C, 7Ј-C); m/z 247 ([M]ϩ, 100%).
Found: C, 72.38; H, 4.82; N, 22.18. Calc. for C15H12N4: C,
72.56; H, 4.87; N, 22.57%.
Diketone 4a
Diketone 4a has been previously reported:8b νmax/cmϪ1 (KBr)
3054 (w, Ar–H), 1709 (s, C᎐O), 1691 (s, C᎐O), 1581 (s, Ar C᎐C),
᎐
᎐
᎐
789 (m, Ar–H), 756 (m, Ar–H); δH(CDCl3, 300 MHz) 8.64 (dd,
J 1.1, 8.0, 1H, H-5), 8.60 (ddd, J 0.9, 1.8, 4.8, 1H, H-6Љ), 8.57
(ddd, J 0.9, 1.7, 4.7, 1H, H-6Ј), 8.26 (dt, J 1.1, 7.8, 1H, H-3Ј),
8.21 (dd, J 1.1, 7.6, 1H, H-3), 8.04 (t, J 7.8, H-4), 7.96 (dt, J 1.7,
7.8, 1H, H-4Ј), 7.86 (dt, J 0.9, 8.0, 1H, H-3Љ), 7.62 (dt, J 1.8, 7.8,
1H, H-4Љ), 7.47 (ddd, J 1.2, 4.8, 7.7, 1H, H-5Ј), 7.24 (ddd, J 1.2,
4.8, 7.5, 1H, H-5Љ); δC(CDCl3, 100 MHz) 197.18 (8-C), 196.78
(7-C), 155.65 (6-C), 154.49 (2Љ-C), 151.98 (2Ј-C), 151.00 (2-C),
149.52 (6Ј-C), 148.97 (6Љ-C), 138.10 (CH, 4-C), 137.12 (CH,
4Ј-C), 136.82 (CH, 4Љ-C), 127.69 (CH, 5Ј-C), 125.09 (CH, 5-C),
124.13 (CH, 5Љ-C), 122.00 (CH, 3-C), 121.79 (CH, 3Ј-C), 120.99
(CH, 3Љ-C); λmax(hexane)/nm 231 (log ε/dm3 molϪ1 cmϪ1 4.49),
255 (4.18 sh), 277 (4.29).
3e
Analogous to the synthesis of 3a, 4e afforded 3e in 31% yield as
a viscous oil; recrystallised (heptane–CHCl3) for analytical
purposes. νmax/cmϪ1 (KBr) 3042 (w, Ar C–H), 1579 (s, Ar C᎐C),
᎐
1562 (s, Ar C᎐C), 837 (m, Ar C–H), 779 (s, Ar C–H); δ (CDCl ,
᎐
H
3
400 MHz) 8.69 (s, 2H, H-5, H-6), 8.59 (br d, J 4.7, 1H, H-6ٞ),
8.35 (dd, J 1.1, 7.9, 1H, H-3Ј), 8.24 (br s, 1H, H-6Љ), 8.08 (dd,
J 1.1, 7.8, H-5Ј), 7.94 (t, J 7.8, 1H, H-4Ј), 7.70 (d, J 7.5, 1H,
H-3Љ), 7.60 (br dd, J 1.8, 7.9, 1H, H-4Љ), 7.52 (dt, J 1.8, 7.6, 1H,
H-4ٞ), 7.38 (dt, J 1.0, 6.9, 1H, H-3ٞ), 7.20 (ddd, J 0.9, 4.0, 7.5,
1H, H-5ٞ), 2.27 (s, 3H, H-7Љ); δC(CDCl3, 100 MHz) 155.74 (C),
155.66 (C), 155.31 (C), 154.60 (C), 152.86 (C), 151.84 (C),
149.31 (CH), 148.86 (CH), 142.60 (CH), 142.39 (CH), 137.72
(CH), 136.69 (CH), 136.22 (C), 132.49 (CH), 123.85 (CH),
123.57 (2CH), 120.76 (CH), 120.35 (CH); m/z 324 ([M]ϩ,
100%), 247 ([M Ϫ C5H3N]ϩ, 8), 245 ([M Ϫ C5H5N]ϩ, 7).
m/z Found: 325.132. C20H15N5 requires 325.133.
4b
Analogous to the synthesis of 4a, 7b afforded 4b in 40% yield;
recrystallisation (CHCl3–pentane, light exclusion) for com-
bustion analysis. Mp 207.5–208.5 ЊC; νmax/cmϪ1 (KBr) 3062 (w,
Ar–H), 1709 (s, C᎐O), 1695 (m, C᎐O), 1583 (m, Ar C᎐C), 1562
᎐
᎐
᎐
(m, Ar C᎐C), 781 (w, Ar–H), 764 (m, Ar–H); δ (CDCl ,
᎐
H
3
300 MHz) 8.82 (dd, J 1.1, 7.9, 1H, H-5), 8.68 (br d, J ca. 4, 1H,
H-6ٞ), 8.58 (br d, J ca. 5, 1H, H-6Ј), 8.55 (br d, J 8.0, 1H,
H-3ٞ), 8.39 (dd, J 1.0, 7.8, 1H, H-3Љ,5Љ), 8.28 (dt, J 1.0, 7.8, 1H,
H-3Ј), 8.24 (dd, J 1.1, 7.6, 1H, H-3), 8.08 (t, J 7.8, 1H, H-4),
7.97 (dt, J 1.7, 7.8, 1H, H-4Ј), 7.81–7.90 (m, 2H, H-3Љ,5Љ, H-4ٞ),
7.76 (t, J 7.8, 1H, H-4Љ), 7.48 (ddd, J 1.2, 4.7, 7.5, 1H, H-5Ј),
7.32 (ddd, J 1.2, 4.8, 7.5, 1H, H-5ٞ); δC(CDCl3, 75 MHz) 197.25
(C), 196.88 (C), 155.87 (C), 155.79 (C), 155.34 (C), 153.78 (C),
152.02 (C), 151.03 (C), 149.57 (CH), 149.14 (CH), 138.05 (CH),
137.80 (CH), 137.19 (CH), 136.84 (CH), 127.75 (CH), 125.16
(CH), 123.84 (CH), 122.06 (CH), 121.85 (CH), 121.42 (CH),
121.04 (CH), 120.94 (CH); m/z 366 (Mϩ, 59%), 338 ([M Ϫ
CO]ϩ, 60), 310 ([M Ϫ 2CO]ϩ, 67), 309 ([M Ϫ C2H3N]ϩ, 68), 232
(C15H10N3, 100), 155 (C10H7N2, 29); λmax(MeCN)/nm 227 (log
ε/dm3 molϪ1 cmϪ1, 4.56), 264 (4.28 sh), 283 (4.35), 302 (4.20 sh).
Found: C, 71.94; H, 3.90; N, 15.31. Calc. for C22H14N4O2: C,
72.12; H, 3.85; N, 15.29%.
3f
Analogous to the synthesis of 3a, 4f afforded 3f in 22% yield
as a golden-coloured oil that was a single substance according
to thin-layer chromatography and 1H NMR spectroscopic
analysis. νmax/cmϪ1 (film) 3056 (m, Ar C–H), 2924 (w, aliphatic
C–H), 1579 (s, Ar C᎐C), 1564 (s, Ar C᎐C), 1429 (m, C–H), 789
᎐
᎐
(s, Ar C–H), 777 (s, Ar C–H), 746 (m, Ar C–H); δH(CDCl3,
400 MHz) 8.69–8.71 (m, 2H, H-5, H-6), 8.59 (br d, J 4.7, 1H,
H-6ٞ), 8.35 (dd, J 1.1, 7.9, 1H, H-3Ј), 8.06 (dd, J 1.1, 7.7, 1H,
H-5Ј), 7.94 (dt, J 1.5, 7.8, 1H, H-4Ј), 7.63 (dt, J 1.5, 7.7, 1H,
H-4Љ), 7.52–7.56 (m, H-3Љ, H-4ٞ), 7.34 (br d, J 7.9, 1H, H-3ٞ),
7.20 (ddd, J 1.2, 4.7, 7.4, 1H, H-5ٞ), 7.04 (d, J 7.7, 1H, H-5Љ),
2.32 (s, 3H, H-7Љ); δC(CDCl3, 100 MHz) 157.76 (C, 1C, 2ٞ-C),
157.15 (C, 1C, 2-CЉ), 155.69 (C, 2C, 2Ј-C; 2ٞ-C), 154.52 (C, 1C,
6Ј-C), 152.96 (C, 1C, 3-C), 151.93 (C, 1C, 2-C), 148.82 (CH,
1C, 6ٞ-C), 142.68 (CH, 1C, 5,6-C), 142.49 (CH, 1C, 6,5-C),
137.54 (CH, 1C, 4Ј-C), 136.45 (CH, 1C, 4Љ-C), 136.30 (CH, 1C,
4ٞ-C), 123.83 (CH, 1C, 3Ј-C), 123.56 (CH, 1C, 5ٞ-C), 122.24
(CH, 1C, 5Љ-C), 120.92 (CH, 1C, 3Љ-C), 120.80 (CH, 1C, 3ٞ-C),
120.19 (CH, 1C, 5Ј-C), 24.20 (CH3, 1C, 7Љ-C); m/z 325 ([M]ϩ,
91%), 324 [M Ϫ H]ϩ, 100), 310 ([M Ϫ CH3]ϩ, 5), 247 ([M Ϫ
C5H4N] Ϫ 11), 220 ([M Ϫ C5H4N Ϫ HCN]ϩ, 9), 206 ([M Ϫ
C5H4N Ϫ CH3CN]ϩ, 7). m/z Found: 325.132. C20H15N5 requires
325.133.
4c
Analogous to the synthesis of 4a, but using 2 equiv. each of
MCPBA and I2 7c afforded 4c in 39% yield; recrystallisation
(CHCl3–heptane, light exclusion) for combustion analysis. Mp
229.5–230.0 ЊC; νmax/cmϪ1 (KBr) 3060 (w, Ar–H), 1718 (s, C᎐O),
᎐
1682 (m, C᎐O), 1581 (m, Ar C᎐C), 758 (w, Ar–H), 764 (m,
᎐
᎐
Ar–H), 1562 (m, Ar C᎐C), 781 (w, Ar–H), 742 (w, Ar–H);
᎐
δH(CDCl3, 300 MHz) 8.55 (br d, J ca. 4.7, 2H, H-6Ј), 8.25 (dt,
J 1.1, 7.8, 2H, H-3Ј), 8.16 (dd, J = 1.1, 6.6, 2H, H-3,5), 8.06 (dd,
J 1.1, 6.6, 2H, H-5,3), 7.96 (dt, J 1.7, 6.0, 2H, H-4Ј), 7.87 (t,
J 7.8, 2H, H-4), 7.48 (ddd, J 1.2, 4.8, 7.6, 2H, H-5Ј); δC(CDCl3,
75 MHz) 196.91 (C, 8-C), 196.54 (C, 7-C), 154.23 (C-6), 151.90
(C-2Ј), 150.97 (C-2), 149.59 (CH, 6Ј-C), 138.21 (CH, 4-C),
137.23 (CH, 4Ј-C), 127.84 (CH, 5Ј-C), 125.08 (CH, 5-C), 122.47
(CH, 3-C), 121.88 (CH, 3Ј-C); m/z 422 (Mϩ, 66%), 394 ([M Ϫ
CO]ϩ, 20), 366 ([M Ϫ 2CO]ϩ, 15), 365 ([M Ϫ CO Ϫ CHO]ϩ, 42),
338 ([M Ϫ 3CO]ϩ, 11), 337 ([M Ϫ 2CO Ϫ CHO]ϩ, 28), 310
([M Ϫ 4CO]ϩ, 36), 309 ([M Ϫ 3CO Ϫ CHO]ϩ, 100);
λmax(MeCN)/nm 225 (log ε/dm3 molϪ1 cmϪ1 4.61), 268 (4.28),
281 (4.20 sh), 293 (4.10 sh), 375 (2.65). Found: C, 67.94;
H, 3.47; N, 13.17. Calc. for C24H14N4O4: C, 68.24; H, 3.34;
N, 13.26%.
3g
Analogous to the synthesis of 3a, 4g afforded 3g in 30% yield;
recrystallised (CH2Cl2–heptane) to give colourless crystals for
combustion analysis. νmax/cmϪ1 (KBr) 3051 (m, Ar C–H), 2922
(w, C–H), 1587 (s, Ar C᎐C), 1574 (m, Ar C᎐C), 1444 (m, C–H),
᎐
᎐
796 (s, Ar C–H); δH(CDCl3, 300 MHz) 8.67–8.69 (m, 2H, H-5,
H-6), 8.41 (br d, J 4.8, H-6Љ), 7.70–7.73 (m, 2H, H-3Љ, H-4Љ),
7.61 (t, J 7.4, 1H, H-4Ј), 7.55 (br d, J 6.4, 1H, H-3Ј), 7.22–7.24
(m, 1H, H-5Љ), 7.08 (d, J 6.5, 1H, H-5Ј), 2.28 (s, 3H, H-7Ј);
δC(CDCl3, 75 MHz) 157.56 (C, 1C), 157.27 (C, 1C), 155.82
(C, 1C), 152.52 (C, 1C), 152.43 (C, 1C), 148.73 (CH, 1C),
142.82 (CH, 1C), 142.63 (CH, 1C), 136.66 (CH, 1C), 136.22
(CH, 1C), 124.23 (CH, 1C), 122.80 (CH, 1C), 122.65 (CH, 1C),
816
J. Chem. Soc., Perkin Trans. 1, 2002, 809–820

View Article Online
4d
4g
Analogous to the synthesis of 4a, 7d afforded 4d in 35%
yield; recrystallisation (CHCl3–pentane, light exclusion) of
colourless rhombohedral crystals for combustion analysis. Mp
To a vigorously stirred solution of 3.78 g (17.8 mmol) 18g in
CH2Cl2 (100 cm3) was added an aq. 1.5 M NaHCO3 solution
(200 cm3) and then m-chloroperbenzoic acid (55% pure, 12.3 g,
39.2 mmol) over ca. 2 h at 0 ЊC. The resulting mixture was
stirred for 5.5 h at 0 ЊC, whereupon water (100 cm3), a saturated
NaHCO3 solution (100 cm3) and CH2Cl2 (50 cm3) were added.
This mixture was briefly stirred, the phases separated, the
organic layer washed with water (4 × 50 cm3) and dried
(Na2SO4). After rotary evaporation of the solvent and column
chromatography (SiO2, CH2Cl2), 1.46 g (36%) of a pale orange
crystalline solid was isolated, and that could be recrystallised
from CH2Cl2–heptane. Mp 138–139 ЊC; νmax/cmϪ1 (KBr) 3072
151.5–152.5 ЊC; νmax/cmϪ1 (KBr) 3059 (w, Ar–H), 1707 (s, C᎐O),
᎐
1689 (s, C᎐O), 1579 (s, Ar C᎐C), 1562 (s, Ar C᎐C), 781
᎐
᎐
᎐
(m, Ar–H), 754 (m, Ar–H); δH(CDCl3, 300 MHz) 8.81 (dd,
J 1.1, 7.9, 1H, H-5), 8.66 (dq, J 0.9, 4.8, 1H, H-6ЉЉ), 8.63 (dd,
J 1.1, 7.9, 1H, H-5Ј), 8.57 (dq, J 0.8, 4.6, 1H, H-6ٞ), 8.52 (dt,
J 1.0, 7.9, 1H, H-3ЉЉ), 8.37 (dd, J 1.0, 7.8, 1H, H-5Љ,3Љ), 8.29 (m,
2H, H-3Ј, H-3), 8.12 (t, J 7.8, 1H, H-4), 8.09 (t, J 7.8, 1H,
H-4Ј), 7.90–7.93 (m, 2H, H-3ٞ, H-3Љ/5Љ), 7.82 (dt, J 1.8, 7.2, 1H,
H-4ЉЉ), 7.76 (t, J 7.8, 1H, H-4Љ), 7.62 (dt, J 1.8, 7.8, 1H, H-4ٞ),
7.30 (ddd, J 1.2, 4.8, 7.5, 1H, H-5ЉЉ), 7.22 (ddd, J 1.2, 4.8, 7.6,
1H, H-5ٞ); δC(CDCl3, 100 MHz) 197.17 (C, 2C, 7-C, 8-C),
155.92 (C, 1C, 2ЉЉ-C), 155.90 (C, 1C, 2Ј-C), 155.84 (C, 1C, 6-C),
155.36 (C, 1C, 6ЉЉ-C), 154.52 (C, 1C, 2Љ-C), 153.71 (C, 1C,
2ЉЉ-C), 151.35 (C, 2C, 6Ј-C, 2-C), 149.16 (CH, 1C, 6ЉЉ-C),
149.03 (CH, 1C, 6Љ-C), 138.16 (CH, 1C, 4-C), 138.04 (CH,
1C, 4Ј-C), 137.86 (CH, 1C, 4Љ-C), 136.83 (CH, 1C, 4ЉЉ,4Љ-C),
136.77 (CH, 1C, 4Љ,4ЉЉ-C), 125.02 (CH, 1C, 5Ј-C), 124.99 (CH,
1C, 5-C), 124.16 (CH, 1C, 5Љ-C), 123.80 (CH, 1C, 5ЉЉ-C),
121.52 (CH, 3C, 3-C, 3-C, 5ЉЉ,3ЉЉ-C), 121.08 (CH, 1C, 3Љ-C),
121.02 (CH, 1C, 3ЉЉ,5ЉЉ-C), 121.00 (CH, 1C, 3ЉЉ-C);
λmax(CHCl3)/nm 256 (log ε/dm3 molϪ1 cmϪ1 4.43 sh), 284
(4.53), 387 (2.13 sh); m/z 443 (Mϩ, 21%), 415 ([M Ϫ CO]ϩ,
93), 387 ([M Ϫ 2CO]ϩ, 64), 386 ([M Ϫ CO Ϫ CHO]ϩ, 100),
232 (C15H10N3, 64), 155 (C10H7N2, 64). Found: C, 72.76;
H, 3.97; N, 15.80. Calc. for C27H17N5O2: C, 73.13; H, 3.86;
N, 15.79%.
(w, Ar–H), 1711 (s, C᎐O), 1693 (m, C᎐O), 1593 (m, Ar C᎐C),
᎐
᎐
᎐
758 (w, Ar–H), 742 (w, Ar–H); δH(CDCl3, 300 MHz) 8.58 (br d,
J ca. 4.8, 1H, H-6Ј), 8.18 (dt, J 1.0, 7.7, 1H, H-3Ј), 7.50 (br d,
J 7.7, 1H, H-3), 7.92 (dt, J 1.7, 7.7, 1H, H-4Ј), 7.77 (t, J 7.7, 1H,
H-4), 7.48 (ddd, J 1.2, 4.7, 7.4, 1H, H-5Ј), 7.32 (br d, J 7.7, 1H,
H-5), 2.41 (s, 3H, H-7); δC(CDCl3, 75 MHz) 197.17 (C), 197.13
(C), 158.72 (C), 151.96 (C), 151.21 (C), 149.42 (CH), 137.10
(CH), 137.06 (CH), 127.70 (CH), 127.67 (CH), 122.14 (CH),
119.55 (CH), 24.11 (CH3); m/z 226 (Mϩ, 49%), 198 ([M Ϫ CO]ϩ,
49), 170 ([M Ϫ 2 CO]ϩ, 41), 169 ([M Ϫ CO Ϫ CHO]ϩ, 100),
92 ([6-Me-C5H4N]ϩ, 97). Found: C, 68.73; H, 4.61; N, 12.28.
Calc. for C13H10N2O2: C, 69.02; H, 4.46; N, 12.38.
Ethanone 7a
Ethanone 7a was prepared as previously reported:8b νmax/cmϪ1
(KBr) 1646 (m, C᎐O), 1601 (s, C᎐C), 1578 (s, C᎐C), 1560 (m,
᎐
᎐
᎐
C᎐C), 1551 (m, C᎐C), 1430 (s, O–H bend), 1258 (m, enol C–O),
᎐
᎐
813 (s, Ar–H), 781 (s, Ar–H), 742 (m, Ar–H); δH(CDCl3, 300
MHz) 8.68–8.70 (H-6E ϩ H-6K or H-6ЉE ϩ H-6ЉK), 8.35–8.36,
4.90 (s, H-7K) (H-6ЉE or H-6E), from the integrals of {H-6E ϩ
H-6K} and H-6ЉE (39 and 32, respectively) 18% : 82% keto–enol
content was calculated; δC(CDCl3, 75 MHz) 198.24 (C, 7-CK),
95.77 (CH, C-8E), 46.87 (CH2, C-8E); λmax(MeOH)/nm 228 (log
ε/dm3 molϪ1 cmϪ1 4.20), 245 (4.10 sh), 279 (4.18), 343 (4.13), 411
(3.66), 432 (3.51 sh); m/z 275 ([M]ϩ, 46%), 247 ([M Ϫ CO]ϩ, 85),
246 ([M Ϫ CHO]ϩ, 100), 156 ([C10H8N2]ϩ, 44), 155 ([C10H7N2]ϩ,
73), 120 ([M Ϫ C10H7N2]ϩ, 21).
4e
Analogous to the synthesis of 4a, 7e afforded 4e in 63% yield as
a red-coloured solid without column chromatography. Mp 121–
122 ЊC; νmax/cmϪ1 (KBr) 3058 (w, Ar–H), 1710 (s, C᎐O), 1691
᎐
(s, C᎐O), 1582 (s, Ar C᎐C), 783 (m, Ar–H), 769 (s, Ar–H), 746
᎐
᎐
(m, Ar–H); δH(CDCl3, 400 MHz) 8.60 (dd, J 1.1, 7.9, 1H, H-5),
8.57 (br d, J ca. 5, 1H, H-6Љ), 8.36 (br s, 1H, H-6Ј), 8.18 (dd,
J 1.1, 7.7, 1H, H-3), 8.14 (d, J 7.9, 1H, H-3Ј), 8.01 (t, J 7.8,
H-4), 7.89 (d, J 7.9, 1H, H-3Љ), 7.71 (dd, J 1.5, 8.0, 1H, H-4Ј),
7.60 (dt, J 1.8, 7.8, 1H, H-4Љ), 7.21 (ddd, J 1.2, 4.8, 8.8, H-5Љ),
2.37 (s, 3H, H-7Ј); δC(CDCl3, 100 MHz) 196.96 (C), 196.90 (C),
155.65 (C), 154.52 (C), 151.02 (C), 150.05 (CH), 149.71 (C),
148.96 (CH), 138.02 (CH), 137.37 (CH), 136.73 (CH), 124.94
(CH), 124.06 (CH), 121.93 (CH), 121.57 (CH), 120.99 (CH),
18.80 (CH3); m/z 303 (Mϩ, 65%), 275 ([M Ϫ CO]ϩ, 59), 247
([M Ϫ 2 CO]ϩ, 69), 246 ([M Ϫ CO Ϫ COH]ϩ, 77), 155
([C10H7N2]ϩ, 100), 92 ([5 Ϫ Me Ϫ C5H3N]ϩ, 84); λmax(MeOH)/
nm 232 (log ε/dm3 molϪ1 cmϪ1 4.13), 246 (4.06 sh), 252 (4.04 sh),
279 (4.08). Found: 303.10. C18H13N3O2 requires 303.10.
7b
Prepared in an analogous manner to 7a, using inverse addition
of lithiated α-picoline–LDA to a suspension of 6b and in 78%
yield; recrystallised (CHCl3–pentane) for combustion analysis.
Mp 171.5–172.5 ЊC; νmax/cmϪ1 (KBr) 3051 (w, alkene C–H),
1645 (m, C᎐O), 1603 (m, C᎐C), 1577 (m, C᎐C), 1566 (s, C᎐C),
᎐
᎐
᎐
᎐
1552 (m, C᎐C), 1427 (s, O–H bend), 806 (m, Ar–H), 777 (s,
᎐
Ar–H), 734 (m, Ar–H); δH(CDCl3, 300 MHz) 8.37 (br d, J 5.0,
H-6ЉE), 7.03–7.07 (m, 2H, H-8E, H-5ЉE, H-5ٞE), 4.92 (s, 2H,
H-8K), from the integrals of {H-8E, H-5ЉE}, H-6ЉE and H-8K
(85, 44 and 41, respectively) 34% : 66% keto–enol content was
calculated; δC(CDCl3, 75 MHz) 198.48 (C, 7-CK), 95.75 (CH,
8-CE), 47.15 (CH2, 8-CK); λmax(MeOH)/nm 223 (log ε/dm3 molϪ1
cmϪ1 4.50), 238 (4.40 sh), 260 (4.32 sh), 285 (4.37), 301 (4.33 sh),
316 (4.23 sh), 343 (4.24), 350 (4.22 sh), 411 (3.81), 428 (3.73 sh);
m/z 352 ([M]ϩ, 46%), 324 ([M Ϫ CO]ϩ, 100), 323 ([M Ϫ CHO]ϩ,
86), 233 ([C15H11N3]ϩ, 63), 155 ([C15H10N3]ϩ, 82), 120 ([M Ϫ
C10H7N2]ϩ, 5). Found: C, 74.75; H, 4.65; N, 15.96. Calc. for
C22H16N4O: C, 74.98; H, 4.58; N, 15.90%.
4f
Analogous to the synthesis of 4a, 7f afforded 4f in 32% yield as
a yellow-coloured oil that solidified. Mp 116–117 ЊC; νmax/cmϪ1
(KBr) 3064 (w, Ar–H), 1710 (s, C᎐O), 1691 (m, C᎐O), 1598 (m,
᎐
᎐
Ar C᎐C), 1588, (m, Ar C᎐C), 756 (w, Ar–H), 740 (m, Ar–H);
᎐
᎐
δH(CDCl3, 270 MHz) 8.59–8.64 (m, 2H, H-5, H-6Љ), 8.19 (dd,
J 1.0, 7.6, H-3), 8.01–8.06 (m, 2H, H-3Ј, H-4), 7.92 (d, J 7.9,
1H, H-3Љ), 7.80 (t, J 7.8, 1H, H-4Ј), 7.63 (dt, J 1.8, 7.7, 1H,
H-4Љ), 7.30 (d, J 9.3, 1H, H-5Ј), 7.24 (ddd, J 1.1, 4.8, 7.5, 1H,
H-5Љ), 2.39 (s, 3H, H-7Ј); δC(CDCl3, 75 MHz) 197.46 (C),
197.04 (C), 158.76 (C), 155.43 (C), 154.54 (C), 151.44 (C),
151.22 (C), 148.88 (CH), 138.07 (CH), 137.02 (CH), 136.98
(CH), 127.52 (CH), 124.89 (CH), 124.16 (CH), 121.84 (CH),
121.18 (CH), 119.01 (CH), 24.10 (CH3); m/z 303 ([M]ϩ, 25), 275
([M Ϫ CO]ϩ, 66), 247 ([M Ϫ 2CO]ϩ, 60), 246 ([M Ϫ CO Ϫ
CHO]ϩ, 100), 155 ([C10H7N2]ϩ 82). Found: 303.1008.
C18H13N3O2 requires 303.10.
7c
Prepared in an analogous manner to 7b and from 6c, but
using two-fold amounts of LDA and α-picoline, giving 92%
of
a yellow-coloured solid that could be recrystallised
(CHCl3–pentane) to afford yellow blocks for analytical pur-
poses. Mp 198–199 ЊC; νmax/cmϪ1 (KBr) 3053 (w, alkene C–H),
1637 (s, C᎐O), 1599 (s, C᎐C), 1570 (s, C᎐C), 1550 (s, C᎐C),
᎐
᎐
᎐
᎐
J. Chem. Soc., Perkin Trans. 1, 2002, 809–820
817

View Article Online
1433 (s, O–H bend), 1294 (m, enol C–O), 1082 (m, enol C–O),
802 (s, Ar–H); δH(CDCl3, 300 MHz) 8.35–8.39 (m, H-6E/K),
7.08–6.99 (m, H-5E/K, H-8E), 4.93 (s, H-8K), from the integrals
of H-6E/K, {H-5E/K, H-8E} and H-8K (12.5, 23.0 and 10, respec-
tively) and the correllation of the signal at δH 8.35–8.39 to
that at δH 7.08–6.99, 32% : 68% ratio of total keto–enol content
was estimated; δC(CDCl3, 75 MHz, total of 35 signals resolved)
198.48 (C, 7-CK), 95.74 (CH, 8-CE), 47.15 (CH2, 8-CK);
λmax(MeOH)/nm 222 (log ε/dm3 molϪ1 cmϪ1 5.06 sh), 258 (3.93),
268 (3.91 sh), 284 (3.88 sh), 349 (4.16), 411 (3.70), 430 (3.63 sh);
m/z 394 ([M]ϩ, 82%), 366 ([M Ϫ CO]ϩ, 100), 365 ([M Ϫ CHO]ϩ,
58), 338 ([M Ϫ 2 CO]ϩ, 3), 337 ([M Ϫ CO Ϫ CHO]ϩ, 7), 288
([M Ϫ CO Ϫ C5H4N]ϩ, 10), 274 ([M Ϫ C5H4NCH2CO]ϩ,
26), 247 ([M Ϫ C5H4NCHO Ϫ CO]ϩ, 30), 246 ([M Ϫ C5H4N2-
CH2O Ϫ CO]ϩ, 68), 92 ([C5H4NCH2]ϩ, 38). Found: C, 72.70;
H, 4.71; N, 14.08. Calc. for C24H18N4O2: C, 73.08; H, 4.60; N,
14.20%.
8-CE), 47.23 (CH2, 1C, 8-CK), 24.39 (CH3, 1C, 7Ј-CK), 23.11
(CH3, 1C, 7Ј-CE); m/z 289 ([M]ϩ, 83%), 261 ([M Ϫ CO]ϩ, 100),
260 ([M Ϫ CHO]ϩ, 89), 155 ([C10H7N2]ϩ, 98), 134 ([M Ϫ
C10H7N2], 62).
7g
Analogous to the preparation of 7b from 5d and 6d in 46% yield
as an orange solid; recrystallisation (hexanes) afforded yellow
blocks for analytical purposes. Mp 68–68.5 ЊC; νmax/cmϪ1 (KBr)
3055 (w, alkene C–H), 1595 (m, C᎐C), 1583 (m, C᎐C), 1556 (s,
᎐
᎐
C᎐C), 1452 (s, O–H bend), 1261 (m, enol C–O), 795 (s, Ar–H),
᎐
742 (m, Ar–H); δH(CDCl3, 300 MHz) 8.63 (br d, J = 4.8, 1H,
H-6ЈE), 7.98 (br d, J 7.9, 1H, H-3ЈE), 7.78 (dt, J 1.8, 7.7, 1H,
H-4ЈE), 7.54 (t, J 7.8, 1H, H-4E), 7.24–7.29 (m, 1H, H-5ЈE), 6.99
(d, J 8.0, 1H, H-3E), 6.84 (d, J 7.4, 1H, H-5E), 6.78 (s, 1H,
H-8ЈE), 2.56 (s, 3H, H-7E), shifts of ketone tautomer visible at
δH 4.74 (s, 2H, H-8K), 2.53 (s, 3H, H-7ЈK), from integrals of
H-8ЈE and H-8K (42 and 12, respectively) 90% : 10% enol–keto
content was calculated; δC(CDCl3, 75 MHz) 202.57 (C, 1C,
7d
Prepared in an analogous manner to 7b, but using 5b,38 6b, and
7-CK), 94.83 (CH, 1C, 8-CE), 47.02 (CH2, 1C, 8-CK); λmax
-
n
(hexane)/nm 229 (log ε/dm3 molϪ1 cmϪ1 3.78 sh), 234 (3.78), 241
(3.75 sh), 285 (3.96), 344 (4.37); m/z 212 ([M]ϩ, 84%), 184 ([M Ϫ
CO]ϩ, 29), 183 ([M Ϫ CHO]ϩ, 51), 134 ([M Ϫ C5H4N]ϩ, 100),
106 ([C5H4NCH2]ϩ, 63). Found: C, 73.27; H, 5.78; N, 13.28.
Calc. for C13H12N2O: C, 73.56; H, 5.70; N, 13.20%.
2 equiv. each of tetramethylpiperidine and BuLi in 28% yield
(rel. to 6b); recrystallisation (CHCl3–pentane) for analytical
purposes. Mp 182.5–183.5 ЊC; νmax/cmϪ1 (KBr) 3054 (w, alkene
C–H), 1637 (m, C᎐O), 1577 (s, C᎐C), 1566 (s, C᎐C), 1542 (s,
᎐
᎐
᎐
C᎐C), 1428 (s, O–H bend), 1265 (m, enol C–O), 792 (m, Ar–H),
᎐
775 (s, Ar–H), 742 (m, Ar–H); δH(CDCl3, 300 MHz) 7.12 (s,
1H, H-7E), 4.97 (s, 2H, H-7K) from integrals of H-7E and H-7K
(1.02 and 0.96, respectively) 32% : 68% keto–enol content was
calculated; λmax(CHCl3)/nm 285 (log ε/dm3 molϪ1 cmϪ1 4.42),
302 (4.33 sh), 318 (4.19 sh), 361 (4.14), 437 (3.03 sh), 606 (1.84);
m/z 429 ([M]ϩ, 100%), 401 ([M Ϫ CO]ϩ, 38), 400 ([M Ϫ CHO]ϩ,
34), 233 ([C15H11N3]ϩ, 50), 232 ([C15H10N3]ϩ, 56), 197
([C10H7N2CH2CO]ϩ, 77), 169 ([C10H7N2]ϩ, 19). Found C, 74.21;
H, 4.54; N, 16.10. Calc. for C27H19N5O: C, 75.51; H, 4.46;
N, 16.31; O, 3.73%.
7h
Analogous to the preparation of 7a, 5e and 6d gave 7h in 40%
yield as a yellow microcrystalline solid after column chroma-
tography (2 × SiO2, 10 : 90, EtOAc–PhMe); recrystallisation
(CH2Cl2–EtOH, then CH2Cl2–heptanes) for analysis. Mp 95–96
ЊC; νmax/cmϪ1 (KBr) 3101 (w, alkene C–H), 1639 (s, C᎐O), 1589
᎐
(vs, C᎐C), 1567 (m, C᎐C), 1531 (s, C᎐C), 1444 (s, O–H bend),
᎐
᎐
᎐
1280 (s, enol C–O), 789 (s, Ar–H), 718 (m, Ar–H), 675 (m,
C–Br); δH(CDCl3, 300 MHz) 8.63 (br d, J 4.8, 1H, H-6ЈE), 7.96
(br d, J 7.9, 1H, H-3ЈE), 7.80 (dt, J 1.8, 7.8, 1H, H-4ЈE), 7.52
(t, J 7.8, 1H, H-4E), 7.29 (ddd, J 1.2, 4.8, 7.6, 1H, H-5ЈE), 7.24
(d, J 7.8, 1H, H-3,5E), 7.16 (d, J 7.9, 1H, H-5,3E), 6.82 (s, 1H,
H-7E), 5.76 (s, 2H, H-7K), other shifts from ketone tautomer
obscured; from the integrals of H-7E and H-7K (1.02 and 1.81,
respectively) a ratio of 53% : 47% was determined; δC(CDCl3,
67.5 MHz) 198.12 (C, 8-CK), 96.91 (CH, 7-CE), 46.61 (CH2,
7-CK); m/z 278, 276 ([M]ϩ, 54%), 248, 250 ([M Ϫ CO]ϩ, 14), 247,
249 ([M Ϫ CHO]ϩ, 17), 198, 200 ([M Ϫ C5H4N]ϩ, 32), 170,
172 ([M Ϫ CHO Ϫ C5H4N]ϩ, 14). Found: C, 52.06; H, 3.32;
N, 10.11. Calc. for C12H9BrN2O: C, 52.01; H, 3.27; N, 10.11%.
7e
Prepared in an analogous manner to 7d, but using 5c, 6a,
1 equiv. tetramethylpiperidine and 2 equiv. nBuLi in 39% yield;
recrystallisation (hexanes) for analytical purposes, although
with considerable loss. Mp 92–93 ЊC; νmax/cmϪ1 (KBr) 2924
(w, C–H), 1639 (s, alkene C᎐C), 1608 (m, Ar C᎐C), 1570 (s, Ar
᎐
᎐
C᎐C), 1560 (s, Ar C᎐C), 1429 (m, O–H), 1257 (m, C–O), 839
᎐
᎐
(m, Ar–H), 773 (s, Ar–H); δH(CDCl3, 300 MHz) 6.98 (s, 1H,
H-8E), 4.90 (s, 2H, H-8K), from the integrals of H-8E and H-8K
(0.87 and 0.99, respectively) 64% : 36% keto–enol content was
calculated; δC(CDCl3, 75 MHz) 198.51 (C, 1C, 7-CK), 95.88
(CH, 1C, 8-CE), 46.47 (CH2, 1C, 8-CK), 18.23 (CH3, 1C, 7Ј-CE),
18.04 (CH3, 1C, 7Ј-CK); m/z 289 ([M]ϩ, 69%), 261 ([M Ϫ CO]ϩ,
92), 260 ([M Ϫ CHO]ϩ, 100), 156 ([C10H8N2]ϩ, 62), 155
([C10H7N2]ϩ, 96), 134 ([M Ϫ C10H7N2]ϩ, 46). Found: C, 74.76;
H, 5.36; N, 14.66. Calc. for C18H15N3O: C, 74.72; H, 5.23
N, 14.52%.
7i
Analogous to the preparation of 7b using 5c, 6d and 2 equiv.
LDA gave 70% yield of 7i; recrystallisation (MeOH). Mp 92–93
ЊC; δH(CDCl3, 270 MHz) 8.71 (br d, J 4.9, 1H, H-6K), 8.63
(br d, J 4.0, 1H, H-6E), from the integrals of H-6K and H-6E
(1.89 and 4.73, respectively) a ratio of 71% : 29% enol–ketone
was calculated; δC(CDCl3, 67.5 MHz) 198.44 (C, 7-CK), 96.17
(CH, 8-CE), 40.06 (CH2, 8-CK), 18.35 (CH3, 7Ј-CK), 18.17 (CH3,
7Ј-CE); m/z 212 ([M]ϩ, 48%), 184 ([M Ϫ CO]ϩ, 8), 183 ([M Ϫ
COH]ϩ, 33), 134 ([M Ϫ C5H4N]ϩ, 63), 106 ([C5H4NCO], 100).
Ethanone 7f
Analogous to the preparation of 7a, but using 5d, 6a, 1 equiv.
tetramethylpiperidine and 2 equiv. nBuLi to give after flash
chromatography 71% yield 7f as a synthetically pure red oil.
νmax/cmϪ1 (KBr) 3057 (w, Ar–H), 2924 (m, C–H), 1702 (w,
6a
C᎐O), 1639 (m, alkene C᎐C), 1595 (m, Ar C᎐C), 1577 (s, Ar
᎐
᎐
᎐
C᎐C), 1558 (s, Ar C᎐C), 1452 (s, O–H), 1427 (m, O–H);
Compound 6a has been previously reported.8b Mp 82–83 ЊC;
νmax/cmϪ1 (KBr) 2995 (w), 2951 (m), 1719 (s), 1593 (s), 1459 (m),
1432 (s), 1326 (s), 1136 (s), 1076 (m), 994 (m), 760 (s);
δH(CDCl3, 300 MHz) 8.69 (br d, J ∼ 4.4, 1H, H-6Ј), 8.61 (dd,
J 1.1, 7.9, 1H, H-3), 8.54 (dd, J 1.0, 8.0, 1H, H-3Ј), 8.14 (dd,
J 1.1, 7.7, 1H, H-5), 7.96 (t, J 7.8, 1H, H-4), 7.85 (dt, J 1.8, 7.8,
1H, H-4Ј), 7.34 (ddd, J 1.2, 4.6, 7.8, 1H, H-5Ј), 4.04 (s, 3H,
H-8); δC(CDCl3, 75 MHz) 165.85 (C, 7-C), 156.47 (C), 155.24
(C), 149.19 (CH), 147.55 (C), 137.88 (CH), 137.06 (CH), 124.98
᎐
᎐
δH(CDCl3, 270 MHz, enol form) 8.70 (br d, J 3.8, 1H, H-6Љ),
8.59 (br d, J 7.9, 1H, H-3Љ), 8.40 (dd, J 1.2, 7.8, 1H, H-3/5), 8.01
(dd, J 1.2, 7.8, 1H, H-5,3), 7.92 (t, J 7.8, 1H, H-4), 7.87 (dt,
J 1.6, 7.7, 1H, H-4Љ), 7.57 (t, J 7.8, 1H, H-4Ј), 7.33 (ddd, J 1.2,
4.8, 7.4, 1H, H-5Љ), 7.06 (J 7.9, 1H, H-5Ј), 6.98 (s, 1H, H-8), 2.05
(s, 3H, H-7Ј), from the integrals of H-8E and H-8K (3.40 and
1.54, respectively) 18% : 82% keto–enol content was calculated;
δC(CDCl3, 75 MHz) 198.45 (C, 1C, 7-CK), 94.81 (CH, 1C,
818
J. Chem. Soc., Perkin Trans. 1, 2002, 809–820

View Article Online
Table 2 Crystal data and parameters of data collection for 3a, c and d
3a
3c
3d
Formula
Mol. weight
Crystal system
Space group
C19H13N5
C28H18N8
466.508
Monoclinic
P 21/c
C29H19N7
465.52
Monoclinic
P 21/a
311.35
Monoclinic
C 2/c
a/Å
b/Å
c/Å
α/Њ
33.8039(31)
7.8999(9)
11.7328(9)
90
7.6365(5)
15.3853(12)
9.7993(6)
90
9.4955(1)
27.5691(3)
17.9795(2)
90
β/Њ
97.615
90
3105.6(5)
8
94.771(5)
90
1147.3(1)
2
92.8582(8)
90
4700.86
8
λ/Њ
Volume/Å3
Z
F(000)
1296
1.33
0.63
484
1.35
0.08
1936
1.32
0.08
Calcd. density /g * cmϪ3
µ /cmϪ1
Crystal size /mm
Absorption correction
Radiation
0.20 * 0.50 * 0.55
φ-scans
CuKα
(λ = 1.54180)
ω/2θ
0.20 * 0.25 * 0.40
φ-scans
MoKα
(λ = 0.71069)
ω/2θ
0.05 * 0.10 * 0.22
none
MoKα
(λ = 0.71069)
Scan type
θmax[Њ]
74.33
3121
2866
2469
26.32
1866
1750
1077
25.03
# Measured reflections
# Independent reflections
# Reflns in refinement
# Variables
51112
16190
10909
991
0.0522
0.0805
0.53/Ϫ0.58
218
164
Final R
0.0382
0.0419
0.20/Ϫ0.12
0.0386
0.0401
0.14/Ϫ0.13
Final Rw
Last max/min in difference map (e × ÅϪ3
)
(CH), 124.28 (CH), 124.20 (CH), 121.67 (CH), 52.82 (CH3,
8-C); m/z 214 ([M]ϩ, 14%), 156 (100), 130 (9). Found: C, 67.23;
H, 4.88; N, 12.88. Calc. for C12H10N2O2: C, 67.28; H, 4.71;
N, 13.08.
X-Ray structural analyses‡
A sample was stuck with glue on a glass fibre and mounted on
the diffractometer. For 3a and c, unit cell parameters were
determined by careful centering of 25 independent, strong
reflections. Data collection was carried out at 293 K on an
Enraf–Nonius CAD4 diffractometer (3a and 3c) or Kappa
CCD area detector (3d), both with a graphite monochromator.
The usual corrections were applied. For 3d, unit cell deter-
mination and integration were carried out using the programs
Denzo and Scalepack.40 All structures were solved by direct
methods using the program SIR92,41 anisotropic least squares
full matrix refinement was carried out on all non-hydrogen
atoms using the program CRYSTALS42 and positions of the
hydrogen atoms determined geometrically. Parameter refine-
ment included reflections with I > 3σ(I ) (3a and c) or I > 2σ(I )
(3d); Chebychev polynomial weights43 were used to complete
the refinements. Scattering factors have been taken from the
International Tables.44 Further techniques and measurement
parameters that are particular to the individual compounds
are presented in Table 2. Fractional co-ordinates have been
deposited at the Cambridge Crystallographic Data Center.
6b
Analogous to 6a using 6-cyano-2,2Ј:6Ј,2Љ-terpyridine,8b how-
ever under reflux conditions and nitrogen gas (10 h), column
chromatography (Al2O3, activity grade III, CH2Cl2) gave 91%
yield of a colourless solid, mp 192–193 ЊC; recrystallized (2 ×
CH2Cl2–heptane), for combustion analysis. Mp 193–194 ЊC;
νmax/cmϪ1 (KBr) 1722 (C᎐O, s), 1581 (Ar C᎐C, m), 1562
᎐
᎐
(C᎐C–N, m), 1427 (Ar C᎐C, s), 1136 (m), 1080 (ester C–O, w),
᎐
᎐
766 (Ar–H, s); δH(CDCl3, 300 MHz) 8.82 (dd, J 1.2, 8.0, 1H,
H-3), 8.71 (br d, J ∼ 4.8, 1H, H-6Љ), 8.61 (dd, J 1.0, 8.0, 1H,
H-3Љ), 8.60 (dd, J 1.0, 7.8, 1H, H-3Ј/5Ј), 8.49 (dd, J 1.0, 7.9, 1H,
H-5Ј/3Ј), 8.17 (dd, J 1.1, 7.7, 1H, H-5), 8.01 (t, J 7.8, 1H, H-4),
7.99 (t, J 7.8, 1H, H-4Ј), 7.87 (dt, J 1.8, 7.7, 1H, H-4Љ), 7.34
(ddd, J 1.2, 4.8, 7.5, 1H, H-5Љ), 4.07 (s, 3H, H-8); δC(CDCl3, 75
MHz) 165.86 (C), 156.48 (C), 156.06 (C), 155.42 (C), 154.39
(C), 149.17 (CH), 147.52 (C), 138.03 (CH), 137.77 (CH), 136.82
(CH), 125.01 (CH), 124.31 (CH), 123.80 (CH), 121.56 (CH),
121.49 (CH), 121.10 (CH), 52.83 (CH3); m/z 291 ([M]ϩ, 44%),
233 (100), 232 (51), 193 (5), 155 (12). Found: C, 69.93; H, 4.58;
N, 14.28. Calc. for C17H13N3O2: C, 70.09; H, 4.50; N, 14.42%.
Acknowledgements
Provision of a Habilitandenstipendium by the Treubel Fond/
Basel to F.H. is gratefully acknowledged. The University of
Basel is thanked for material assistance, while the Fa. Novartis
AG and Dow Elanco/UK provided material assistance. The aid
of Dr D. Smith and Dr H.-M. Schiebel in measuring particular
spectra is appreciated.
6c
Analogous to 6a using 2,2Ј-dicyano-6,6Ј-bipyridine39 however
in PhMe–MeOH under reflux conditions and nitrogen gas
(10 h), hydrolysis by stirring overnight with a 1 : 2 : 1 CH2Cl2–
MeOH–2 M. aq. HCl mixture, 87% yield; recrystallisation
(CH2Cl2–EtOH) for combustion analysis. Mp 188–191 ЊC; νmax
/
‡ CCDC reference number(s) 170985–170987. See http://www.rsc.org/
suppdata/p1/b1/b107751a/ for crystallographic files in .cif or other elec-
tronic format.
cmϪ1 (KBr) 2924 (w), 1739 (m, C᎐O), 1252 (s, C–O), 766 (Ar–
᎐
H); δH(CDCl3, 300 MHz) 8.75 (dd, J 1.1, 7.8, 2H, H-5), 8.17
(dd, J 1.1, 7.8, 2H, H-5), 8.00 (t, J 7.9, 2H, H-3), 4.04 (s, 6H,
H-8); δC(CDCl3, 75 MHz) 165.65 (C, 7-C), 155.44 (C), 147.50
(C), 138.06 (CH), 125.46 (CH), 124.82 (CH), 52.86 (CH3); m/z
272 ([M]ϩ, 11%), 241 ([M Ϫ OCH3]ϩ, 11), 240 ([M Ϫ MeOH]ϩ,
14), 214 ([M Ϫ CO2CH3]ϩ, 100). Found: C, 62.14; H, 4.65; N,
10.50. Calc. for C14H12N2O4: C, 61.76; H, 4.44; N, 10.29%.
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J. Chem. Soc., Perkin Trans. 1, 2002, 809–820