Pyrrolizine-1,3-dione

Article abstract of DOI:10.1039/c0ob00116c

Pyrrolizine-1,3-dione 4 was made by oxidation of the alcohol 2 using pyridinium chlorochromate. The dione 4 shows ketone properties (e.g. formation of DNP derivative 11) and, in common with other pyrrolizinones, the lactam unit is readily ring-opened by methanol under basic conditions. The active methylene unit of 4 couples readily with diazonium salts to provide the hydrazone 15 whose structure was confirmed by X-ray crystallography. The 'Meldrumsated' derivative 18 exists exclusively as the tautomer 18F; flash vacuum pyrolysis (FVP) of 18 at 700°C gives the pyronopyrrolizine 20 exclusively. Reaction of 4 with DMF acetal gives the dimethylaminomethylene derivative 22 which exists as a mixture of rotamers at room temperature.

Full text of DOI:10.1039/c0ob00116c

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Pyrrolizine-1,3-dione†
Hamish McNab,* James Montgomery, Simon Parsons and David G. Tredgett
Received 13th May 2010, Accepted 25th June 2010
DOI: 10.1039/c0ob00116c
Pyrrolizine-1,3-dione 4 was made by oxidation of the alcohol 2 using pyridinium chlorochromate. The
dione 4 shows ketone properties (e.g. formation of DNP derivative 11) and, in common with other
pyrrolizinones, the lactam unit is readily ring-opened by methanol under basic conditions. The active
methylene unit of 4 couples readily with diazonium salts to provide the hydrazone 15 whose structure
was confirmed by X-ray crystallography. The ‘Meldrumsated’ derivative 18 exists exclusively as the
tautomer 18F; flash vacuum pyrolysis (FVP) of 18 at 700 ◦C gives the pyronopyrrolizine 20 exclusively.
Reaction of 4 with DMF acetal gives the dimethylaminomethylene derivative 22 which exists as a
mixture of rotamers at room temperature.
nitrogen through the solution. The dione 4 is characterised by its
Introduction
methylene signal at dH 3.54 in the 1H NMR spectrum. Pyridinium
dichromate oxidation of 2 was also successful but the yield was
significantly lower.
In previous papers, we have reported facile routes to pyrrolizin-
3-ones 1 using flash vacuum pyrolysis (FVP) as the key step.1 We
have also shown that the 1-hydroxy derivative 2 is easily made from
pyrrolizin-3-one by sequential addition of HCl and quenching of
the highly reactive 1-chloro compound 3 by water.2 Here, we report
an optimised method for the oxidation of 2 into pyrrolizine-1,3-
dione 4 and our studies of the properties of this unusual dione.
Compound 4 potentially shows pyrrole, ketone, amide and active
methylene functionality. Open-chain analogues such as pyrrolyl
b-ketoanilides have been used as yellow couplers with potential
applications in colour photography.3 However, 4 is a unique
system; electron donation from the bridgehead nitrogen atom into
the lactam system is compromised by its contribution to the 6p
system of the pyrrole (and its associated 1-keto functionality). The
carbonyl groups are therefore likely to show unusual properties.
Other oxidation methods met with little success (ESI†). For
example, Dess–Martin conditions5 gave unidentified decomposi-
tion products and manganese dioxide oxidation6 showed only low
conversion to 4. Swern oxidation7 gave the ylide 5 in 3% yield.
This compound was characterised by the S–Me singlet at dH 3.01
(cf. ref. 8) and by the ylide carbon resonance at dC 64.87; although
the value of latter parameter is variable in sulfonium ylides,9,10
the observed figure occurs in the expected range for dicarbonyl-
stabilised examples.9
The ylide 5 is likely to be formed by initial oxidation to the dione
4 followed by in situ reaction with an activated Swern intermediate
such as 6 (Scheme 1).
Scheme 1
Results and discussion
We have also explored two potential gas-phase routes to 4.
The anticipated retro-ene decomposition of 7 (cf. ref. 11) by
FVP at 750 ◦C gave only a trace of the dione 4 together with
some pyrrolizin-3-one 1 and higher molecular-weight products.
Dehydration to pyrrolizin-3-one 1 was the only process when the
alcohol 2 was subjected to FVP at 200 ◦C over a plug of zinc
oxide, conditions which generally promote dehydrogenation of
secondary alcohols to ketones.12
In contrast to pyrrolizinones which are generally highly
coloured, pyrrolizine-1,3-dione 4 is a slightly yellow, highly
crystalline solid. It shows carbonyl absorptions at 1698 and
1760 cm-1. Since dihydropyrrolizin-1-one 8 is reported13 to have
Our optimised route to 4 involves oxidation of the secondary al-
cohol functionality of 2 with pyridinium chlorochromate (PCC),4
providing 4 in 68% yield. Efficient agitation of the reaction mixture
throughout the oxidation is essential for good yields and this is
best achieved by a combination of magnetic stirring and bubbling
School of Chemistry, The University of Edinburgh, West Mains Road,
Edinburgh, UK, EH9 3JJ. E-mail: H.McNab@ed.ac.uk; Fax: +44 131 650
4743; Tel: +44 131 650 4718
† Electronic supplementary information (ESI) available: Experimental,
V.T. NMR data for 22. X-Ray structure table. CCDC reference numbers
777142–777143. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c0ob00116c
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nmax 1705 cm-1 and the isomeric dihydropyrrolizin-3-one14 9 has
nmax 1734 cm-1, it seems likely that the lactam carbonyl of 4 has
nmax 1760 and the ketone nmax 1698 cm-1. This appears to be an
unusual example of a lactam having a higher frequency absorption
than a ketone in a similar structural environment. Crystals are
disordered (see Experimental section) but the results of an X-ray
crystallographic analysis confirm the planarity of the system and
show that the dione is the major tautomeric form in the solid state.
In solution, pyrrolizine-1,3-dione 4 appears to adopt the keto
tautomer exclusively. In contrast, the tetrahydro-derivative 10 is
known to exist as a 1 : 1 mixture of keto and enol tautomers in
DMSO solution15 though it apparently exists as the keto tautomer
in chloroform.16
Scheme 2 Reagents and conditions: (i), H2/Pd/C/ethanol (one of the
enantiomeric pairs shown).
Under appropriate conditions, pyrrolizine-1,3-dione 4 can show
typical ketone properties; for example reaction with Brady’s
reagent gives the hydrazone 11 (89%). The amide functionality
survives the acid conditions used in this reaction. Unusually for
typical lactams, but in common with other pyrrolizin-3-ones (such
as 1), the dione 4 is very reactive under basic conditions and
quantitative ring opening to the b-ketoester 12 occurs in methanol
containing a drop of Hu¨nig’s base.
Scheme 3 Reagents and conditions: (i) [2H4]methanol; (ii) [2H]TFA;
(iii) benzenediazonium tetrafluoroborate, Hu¨nig’s base, CH2Cl2; (iv)
methoxymethylene Meldrum’s acid 17, Hu¨nig’s base, CH2Cl2; (v) DMF
dimethyl acetal, CHCl3.
Pyrrolizin-3-ones can be readily hydrogenated under mild het-
erogeneous catalytic conditions17 and the dione 4 behaves similarly,
providing a 88 : 12 mixture of 10 and 13 (Pd/C, 3 atm H2 in ethyl
acetate). The isomers 13 and 14 can be readily distinguished by
their characteristic NMR spectra,18 and it was clear that the trans-
isomer 14 was not formed. A possible mechanism involves initial
hydrogenation of the pyrrole ring to the tetrahydro compound 10
followed by reduction of the ketone function via a small amount
of the enol tautomer at its less hindered face (Scheme 2).17
Fig. 1 Plot of the hydrazone 15, showing the crystallographic numbering
The dione 4 shows extensive active methylene chemistry. The
scheme.
CH2 group exchanges rapidly in [2H4]methanol but rather more
slowly under acidic conditions ([2H]TFA; t1 ca. 3 h). Under neutral
The C(1)–O(1) bond distance [1.2236(14) A] is significantly longer
than that of the 3-carbonyl group [C(3)–O(3), 1.2023(14) A]. This
is an unusual example of a ketone carbonyl bond length being
longer than an amide in similar structural environments,19 but
is consistent with the I. R. data reported above. The molecule
as a whole is planar [mean deviation from best plane 0.062 A;
maximum deviation from best plane 0.20 A at O(1)]. By compar-
ison with pyrrolizin-3-one 1 itself,20 the formal single bonds in
the ‘pyrrole’ ring [N(4) through to C(8)] of 15 are shorter, and
the formal double bonds are longer owing to conjugation of the
N(4) lone pair through the pyrrole ring to the 1-carbonyl group.
˚
2
˚
conditions, the exchange presumably takes place via traces of
an enol tautomer, which suggests that keto-enol tautomerism is
rapid. Chemical shifts are almost unchanged in TFA solution
(see Experimental section), which suggests that relatively little
protonation takes place under these conditions.
˚
˚
Azo-coupling of 4 with benzenediazonium tetrafluoroborate
in dichloromethane containing a trace of Hu¨nig’s base provides
the hydrazone 15 quantitatively (Scheme 3). Its crystal structure
(Fig. 1) shows internal hydrogen bonding between H(3) and O(1)
◦
˚
˚
[H(3)–O(1), 2.20 A; N(3)–O(1), 2.8588(12) A, angle at H 131 ].
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Structural parameters for the ketohydrazone unit of 15 as a whole
[N(3)–N(2)–C(2)–C(1)–O(1)] are broadly comparable to those of
related compounds, such as the hydrazonopyrrolone 16.21
pyrrolizinedione rather than its lactam carbonyl group, with very
high selectivity.
When the dione 4 is allowed to stand in a chloroform solution
of DMF dimethyl acetal, at room temperature, the dimethy-
laminomethylene product 22 is obtained in 95% yield (Scheme 3).
In a similar fashion to dimethylaminomethylene Meldrum’s acid
Reaction of the dione 4 with methoxymethylene Meldrum’s
acid 17 in dichloromethane containing a drop of Hu¨nig’s base
provides the ‘Meldrumsated’ product 18 (81%) (Scheme 3).22
Various tautomeric structures of this product are possible (18A–
F). 13C NMR spectroscopy shows only 4 CH resonances which
eliminates the non-conjugated tautomers 18B and 18C. Two
carbonyl quaternary signals at dC 162.42 are in the region expected
for the dioxanedione moiety (thereby eliminating 18D and 18E).
The 1-hydroxy tautomer 18A would be expected to show a
‘normal’ pyrrolizin-3-one lactam resonance23 at about dC 165 and
since the two remaining C–O quaternaries are at dC 177.81 and
176.91 the tautomeric structure of 18 is most likely to be 18F.
23,25 which shows restricted rotation around C–N and C
C
bonds, compound 22 can exist in potentially interconverting Z and
E isomers (22A and 22B respectively), both of which can undergo
1
C–N rotation. Its room temperature H NMR spectrum shows
two pairs of signals for the N-methyl groups due to restricted C–N
rotation of the two isomers and one pair for the exocyclic methine
proton due to restricted C C rotation; each pair coalesces to
a single resonance at higher temperatures. These parameters are
discussed in the ESI.†
By comparison with the FVP reactions of other Meldrum’s
acid derivatives,24 FVP of 18 was expected to generate the ketene
intermediate 19 which could electrocyclise onto either of the
carbonyl groups to give one (or both) of the pyronopy◦rrolizinones
20 and 21 (Scheme 4).22 In the event, FVP of 18 at 700 C provided
the single pyronopyrrolizinone 20 (96%), the first example of this
ring system. In this case, the presence of a typical pyrrolizin-3-one
carbonyl resonance at dC 166.81, and the absence of a pyrrolizin-1-
one carbonyl signal at ca. dC 180, are particularly diagnostic. The
ketene 19 therefore cyclises onto the ketone carbonyl group of the
Conclusions
We conclude that pyrrolizine-1,3-dione 4 can be conveniently
made in two steps from pyrrolizin-3-one 1. The dione is stable
under acidic conditions but rapidly ring opens in the presence
of base. The two carbonyl groups of 4 have anomalous IR
stretches, and their unusual nature is also reflected in the crystal
structure of the hydrazone15. Dione 4 displays chemical properties
typical of b-ketoamides – in particular a rich variety of active
methylene chemistry. Its synthetic utility is exemplified by a two-
step transformation into the tricycle 20, the first example of this
ring system.
Experimental
1H and 13C NMR spectra were recorded at 250 or 63 MHz
respectively for solutions in [2H]chloroform unless otherwise
stated. Coupling constants are quoted in Hz. 13C NMR signals
refer to one CH resonance unless otherwise stated. Mass spectra
were recorded under electron impact conditions.
Scheme 4 Reagents and conditions: (i) FVP, 700 ◦C.
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Pyrrolizine-1,3-dione 4
products which was not separated. From the NMR spectra of the
mixture, these products were identified as pyrrolizidine-1,3-dione
10 (88%) dH 4.09 (1H, m), 3.83 (1H, m), 3.26 (1H, d, J 21.2),
A solution of 1,2-dihydro-1-hydroxypyrrolizin-3-one 22 (0.10 g,
0.7 mmol) in dichloromethane (5 cm3) was added dropwise to
a vigorously stirred suspension of pyridinium chlorochromate
(0.63 g, 2.9 mmol) in dichloromethane (5 cm3).4 The flask was
wrapped in aluminium foil to ensure the absence of light, and a flow
of nitrogen was constantly bubbled through the suspension to keep
it mobile. The mixture was allowed to stir at room temperature for
1 h and was then filtered through a 1 cm silica plug. The filtrate
was concentrated, the resulting solid was washed with hexane, and
dried in vacuo to give pure pyrrolizine-1,3-dione 4 0.069 g (68%)
as a yellow crystalline solid, mp 150–151 ◦C (from ethyl acetate),
(Found: M+ 135.0321. C7H4NO2 requires M 135.0320) (Found: C
61.5; H 3.9; N 9.9%. C7H4NO2 requires C 62.2; H 3.7; N 10.4%);
2
3.13 (1H, m), 2.89 (1H, dd, 2J 21.2, nJ 1.5), 1.80–2.15 (3H, m) and
1.60 (1H, m); dC 205.84 (quat), 170.34 (quat), 69.99, 45.49 (CH2),
43.21 (CH2), 26.47 (CH2) and 25.80 (CH2) (spectra compatible
with literature data15,16,26) and cis-1-hydroxypyrrolizidin-3-one 13
(12%) dC 173.19 (quat), 67.87, 66.84, 45.49 (CH2) 41.40 (CH2),
27.10 (CH2) and 22.92 (CH2) (spectrum compatible with literature
data17,18).
2-(Phenylhydrazono)-pyrrolizine-1,3-dione 15
Benzenediazonium tetrafluoroborate (28 mg, 0.15 mmol) was
added to a solution of pyrrolizine-1,3-dione 4 (20 mg, 0.15 mmol)
in dichloromethane (0.5 cm3). N,N-Di-isopropylethylamine was
added dropwise to this stirred suspension until all solid had
dissolved. After 15 min stirring a precipitate had formed, so the
solvent was evaporated and the organic material was dissolved
in ether leaving behind all inorganic material. Removal of the
solvent yielded 2-(phenylhydrazono)-pyrrolizine-1,3-dione 15 as
an intense orange solid (43 mg, 99%), (Found: M+ 239.0695.
dH 7.44 (1H, dd, 3J 2.9 and 4J 0.9), 6.89 (1H, dd, 3J 3.5, J 0.9),
4
6.75 (1H, dd, 3 J 3.5, 2.9) and 3.55 (2H, s); dC 182.07 (quat), 165.11
(quat), 136.14 (quat), 121.03, 118.55, 112.09 and 44.62 (CH2); dH
([2H]TFA) 7.39 (1H, dd, J 3.0, J 0.8), 6.93 (1H, dd, J 3.7, J
0.8), 6.67 (1H, dd, 3J 3.7 and 3.0) and 3.64 (2H, s); dC ([2H]TFA)
186.24 (quat), 167.25 (quat), 134.77 (quat), 122.36, 120.97, 116.03
and 43.64 (CH2); m/z 135 (M+, 100%), 94 (52), 93 (84) and 65 (42);
nmax 3111, 2959, 2360, 1760, 1698, 1551, 1432, 1361, 1289, 1251,
1130, 1022, 937, 915, 893, 857, 775 and 601 cm-1.
3
4
3
4
◦
C13H9N3O2 requires M 239.0695); mp 113 C: dH 13.22 (1H, s),
3
3
7.43–7.51 (3H, m), 7.38 (2H, t, J 7.3), 7.21 (1H, t, J 7.3), 6.91
3
3
Oxidation of a solution of 2 (0.10 g, 0.7 mmol) in DCM
(1.25 cm3) with PDC (0.44 g) under similar conditions for 3 h
yielded pyrrolizine-1,3-dione 4 (0.025 g, 25%) after workup.
(1H, d, J 3.4) and 6.60 (1H, t, J 3.3); dC 176.00 (quat), 158.34
(quat), 140.83 (quat), 132.53 (quat), 129.39 (2CH), 127.15 (quat),
126.00, 119.73, 118.78, 115.95 (2CH) and 113.40; m/z 169 (M+
100%), 162 (10), 147 (63), 103 (20), 94 (98), 77 (100) and 51 (46).
1-(2,4-Dinitrophenylhydrazono)-1,2-dihydropyrrolizin-3-one 11
5-(3-Hydroxy-1-oxo-1H-pyrrolizin-2-ylmethylene)-2,2-dimethyl-
Brady’s reagent (2 drops) was added to a solution of pyrrolizine-
1,3-dione 4 (20 mg, 0.15 mmol) in ethyl acetate. The precipi-
tate was filtered off to give 1-(2,4-dinitrophenylhydrazono)-1,2-
dihydropyrrolizin-3-one 11 (42 mg, 89%); mp 189 ◦C; (Found: M+
315.0605. C13H9N5O5 requires M 315.0604) dH 11.41 (1H, s), 9.19
(1H, d, 3J 9.2), 8.40 (1H, dd, 3J 9.5 and 4J 2.5), 8.08 (1H, d, 3J 9.5),
7.45 (1H, d, J 3.0), 7.23 (1H, d, J 3.7), 6.83 (1H, m) and 3.54
(2H, s); dC 166.0 (quat), 144.7 (quat), 139.1 (quat), 130.2, 123.4,
121.1, 116.5, 116.4, 111.7 and 40.7 (CH2) (3 quaternary signals
not apparent); m/z 315 (M+, 86%), 193 (45) and 84 (100).
1,3-dioxane-4,6-dione 18
5-Methoxymethylene-2,2-dimethyl-1,3-dioxane-4,6-dione
17
(28 mg, 0.15 mmol) was added to a solution of pyrrolizine-1,3-
dione 4 (20 mg, 0.15 mmol) in dichloromethane (1 cm3). The
solution was stirred for 15 min then hexane (5 cm3) was added
until a red oil settled; the yellow solvent layer was discarded.
The red oil was then treated with dilute hydrochloric acid (2M,
2 cm3) and the organics extracted into dichloromethane. Removal
of the solvent yielded 5-(3-hydroxy-1-oxo-1H-pyrrolizin-2-
ylmethylene)-2,2-dimethy◦l-1,3-dioxane-4,6-dione 18 (42 mg, 81%)
as a red solid, mp 156 C; (Found: M+ 289.0589. C14H11NO6
3
3
Methyl 3-oxo-3-(1H-pyrrol-2-yl)-propionate 12
3
requires M 289.0581); dH 8.42 (1H, s), 7.47 (1H, d, J 2.5), 6.98
3
3
Pyrrolizine-1,3-dione 4 (20 mg, 0.15 mmol) was dissolved in
methanol (1 cm3) and N,N-di-isopropylethylamine (1 drop) was
added. The solution became deep red in colour, then the solvent
was removed to yield met◦hyl 3-oxo-3-(1H-pyrrol-2-yl)-propionate
12 (25 mg, 99%), bp 65 C (0.3 Torr), as a red oil; (Found: M+
167.0577. C8H9NO3 requires M 167.0577) dH 9.73 (1H, br. s), 7.10
(1H, m), 6.96 (1H, m), 6.31 (1H, dt, 3J 3.9 and 2.3), 3.82 (2H, s)
and 3.75 (3H, s); dC 181.74 (quat), 167.98 (quat), 131.13 (quat),
125.97, 118.11, 111.23, 52.50 (CH3) and 45.13 (CH2); m/z 167 (M+
19%), 94 (100), 66 (38) and 44 (35).
(1H, d, J 3.4), 6.58 (1H, dd, J 3.4 and 2.5) and 1.78 (6H, s);
dC 177.81 (quat), 176.91 (quat), 162.42 (2 quat), 144.62, 130.97
(quat), 122.78, 119.47, 117.72, 104.98 (2 quat), 96.18 (quat) and
26.75 (2CH3); m/z 289 (M+, 5%), 231 (57), 159 (100), 94 (38) and
57 (61).
4-Oxa-8a-azacyclopenta[a]indene-5,8-dione 20
5-(3-Hydroxy-1-oxo-1H-pyrrolizin-2-ylmethylene)-2,2-dimethyl-
1,3-dioxane-4,6-dione 18 (20 mg, 0.07 mmol) was sublimed at
110 ◦C (0.034 Torr) over 15 min through a silica furnace tube
held at 700 ◦C by an electrical tube furnace. 4-Oxa-8a-aza-
cyclopenta[a]indene-5,8-dione 20 was collected in a liquid nitrogen
trap situated at the exit poi◦nt of the furnace, as a dark orange
solid (13 mg, 96%), mp 168 C (decomp); (Found: M+ 187.0264.
C10H5NO3 requires M 187.0271); dH 7.51 (1H, d, 3J 9.5), 7.15 (1H,
dd, 3J 4.0 and 4J 0.8), 6.51 (1H, dd, 3J 4.0 and 4J 0.8), 6.21 (1H,
Hydrogenation of Pyrrolizine-l,3-dione 4
Palladium on charcoal (5%, 10 mg) was added to a solution of
pyrrolizine-1,3-dione 4 (20 mg, 0.15 mmol) in ethyl acetate (20 cm3)
and the mixture was hydrogenated at 3 atm for 3 h. The catalyst
was filtered (celite) and the solvent removed to give a mixture of
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t, 3J 4.0) and 6.03 (1H, d, 3J 9.5); dC 166.81 (quat), 159.12 (quat),
158.80 (quat), 137.98, 127.65 (quat), 121.47, 116.75, 114.26, 108.90
and 106.77 (quat); m/z 187 (M+, 71%), 159 (100), 103 (32) and 94
(39).
Acknowledgements
We are grateful to Dr R. D. L. Johnstone for the crystal structure,
and to the EPSRC for a research studentship (to J. M.) and for the
provision of the diffractometer.
2-(1-Dimethylaminomethylene)-pyrrolizine-1,3-dione 22
References
DMF dimethyl acetal (3 drops) was added to a solution of
pyrrolizine-1,3-dione 4 (20 mg, 0.015 mmol) in chloroform
(1 cm3). The solution instantly became black and the solvent
was removed leaving a black solid. The residue was dissolved in
dichloromethane and decolourising charcoal (0.5 g) was added;
after filtration through celite the solvent was removed to give 2-(1-
dimethylaminomethylene)-pyrrolizine-1,3-dione 22 (27 mg, 95%),
mp 103–104 ◦C as an off white solid. This was a 1 : 1 mixture
of the E/Z isomers; (Found: M+ 190.0742. C10H10N2O2 requires
M 190.0742); dH 7.82 (1H, s), 7.72 (1H, s), 7.65–7.67 (2H, m),
7.05–7.08 (2H, m), 6.86 (2H, m), 4.13 (3H, m), 4.03 (3H, s) and
3.85 (6H); dC 184.1 (quat), 183.7 (quat), 167.2 (2 quat), 135.6
(quat), 134.5 (quat), 122.9, 121.3, 120.0, 119.4, 118.5, 116.3, 115.3,
27.6 (2CH3), 26.5 (CH3) and 25.7 (CH3) (other signals broad or
overlapping); m/z 190 (M+, 68%), 94 (100), 85 (42) and 65 (38).
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5370–5376.
˚
space group Pbcn. a = 5.1445(9), b = 14.134(2), c = 8.0639(15) A,
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3
˚
V = 586.35(17) A at T = 150 K. Z = 4. Data were collected
with Cu-Ka radiation on a Stoe Stadi-4 four circle diffractometer
equipped with an Oxford Cryosystems low temperature device.
The structure was solved by direct methods (SIR92)27 and refined
against F2 using all data (Shelxl-97).28 The final R factor based on
F and data with F > 4s(F) was 0.0325. The molecule is disordered
about a crystallographic two-fold axis which passes through the
atoms C2 and C6. This averages the lengths and angles formed
between chemically inequivalent atoms, and so these should not
be interpreted. This determination is used only to show that 4 is
planar and to establish the tautomeric form in the solid-state.
17 X. L. M. Despinoy and H. McNab, Org. Biomol. Chem., 2009, 7, 4502–
4511.
18 R. P. Beckett, S. G. Davies and A. A. Mortlock, Tetrahedron:
Asymmetry, 1992, 3, 123–136.
19 F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen and
R. Taylor, J. Chem. Soc., Perkin Trans. 2, 1987, S1–S19.
20 F. Blockhuys, S. L. Hinchley, H. E. Robertson, A. J. Blake, H. McNab,
X. L. M. Despinoy, S. G. Harris and D. W. H. Rankin, J. Chem. Soc.,
Perkin Trans. 2, 2001, 2195–2201.
21 A. J. Blake, H. McNab and L. C. Monahan, J. Chem. Soc., Perkin Trans.
1, 1991, 701–704.
22 C.f. P. A. Derbyshire, G. A. Hunter, H. McNab and L. C. Monahan, J.
Chem. Soc., Perkin Trans. 1, 1993, 2017–2025.
23 Review, (a) H. McNab and C. Thornley, Heterocycles, 1994, 37, 1977–
2008; (b) J. Loeffler and R. Schobert, J. Chem,. Soc., Perkin Trans. 1,
1996, 2799–2802.
24 M. A. Gaber and H. McNab, Synthesis, 2001, 2059–2074.
25 A. J. Blake, H. McNab and L. C. Monahan, J. Chem. Soc., Perkin Trans.
2, 1991, 2003–2010.
26 R. Schobert and R. Wicklein, Synthesis, 2007, 1499–1502.
27 A. Altomare, G. Cascarano, C. Giacovazzo and A. Guagliardi, J. Appl.
Crystallogr., 1993, 26, 343–350.
28 G. M. Sheldrick, SHELXTL-XP version 6.01, 2001 University of
Gottingen, Germany and Bruker-AXS, Gottingen, Germany and
Madison, Wisconsin, USA.
Crystal data for 15. C13H9N3O2 M = 239.23, monoclinic, space
˚
group P21/c. a = 6.1911(3), b = 7.8957(4), c = 21.7772(10) A,
◦
3
˚
b = 91.924(3) , V = 1063.94(9) A at T = 150 K. Z = 4.
Data were collected with Mo-Ka radiation on a Bruker Apex
CCD diffractometer equipped with an Oxford Cryosystems low
temperature device. The structure was solved by direct methods
(SIR92) and refined against F2 using all data (Crystals).29
In both structures non-H atoms were modelled with anisotropic
displacement parameters and H-atoms were placed in calculated
positions. Further crystal and refinement data are available in the
ESI.†
29 P. W. Betteridge, J. R. Carruthers, R. I. Cooper, K. Prout and D. J.
Watkin, J. Appl. Crystallogr., 2003, 36, 1487.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 4383–4387 | 4387
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