Solid-supported heterocumulenes: Preparation and crystal structure of azaaplysinopsins

Article abstract of DOI:10.1021/jo962174y

Annulation of carbodiimides 6a,b, on alumina solid support, selectively gives (Z)-hydantoins 8a,b determined on the basis of X-ray analysis while thermal cyclization affords, after purification, 8a,b with imidazolones 10a,b. In the imidazopyrimidine series, thermal reaction of heterocumulenes 6d yields, via a Dimroth rearrangement, the dipyridoimidazolic compound 11. In all cases, mechanisms for the observed cyclizations have been proposed.

Full text of DOI:10.1021/jo962174y

J . Org. Chem. 1997, 62, 4085-4087
4085
Solid -Su p p or ted Heter ocu m u len es: P r ep a r a tion a n d Cr ysta l
Str u ctu r e of Aza a p lysin op sin s
J ean M. Chezal,1a Gre´gory Delmas,1a Sylvie Mavel,1b Hamed Elakmaoui,1c J acques Me´tin,1a
Anna Diez,1d Yves Blache,1c Alain Gueiffier,1b Mario Rubiralta,1d J ean C. Teulade,1a and
Olivier Chavignon*,1a
De´partement d’Analyse Structurale et de Pharmacologie, Faculte´ de Pharmacie, 28, Pl. H. Dunant, BP 38,
63001 Clermont-Fd Cedex 1, France, Laboratoire de Chimie The´rapeutique, Faculte´ de Pharmacie, 34
Avenue Monge, 37200 Tours, France, Laboratoire de Chimie Organique, Faculte´ de Pharmacie 15, Avenue
Ch. Flahault, 34060 Montpellier, France, and Laboratori de Qu´ımica Orga`nica, Facultat de Farma`cia,
Universitat de Barcelona, 08028-Barcelona, Spain
Received November 20, 1996X
Annulation of carbodiimides 6a ,b, on alumina solid support, selectively gives (Z)-hydantoins 8a ,b
determined on the basis of X-ray analysis while thermal cyclization affords, after purification, 8a ,b
with imidazolones 10a ,b. In the imidazopyrimidine series, thermal reaction of heterocumulenes
6d yields, via a Dimroth rearrangement, the dipyridoimidazolic compound 11. In all cases,
mechanisms for the observed cyclizations have been proposed.
In tr od u ction
Aplysinopsin (1) (Figure 1), isolated from the sponge
Aplysinopsis reticulata (Dictyoceartida),2 has been shown
to be active as a specific cytotoxin of cancer cells3 and to
affect neurotransmission.4 The classical approach to the
synthesis of C-5 unsaturated hydantoins such as 2 is
F igu r e 1.
based on the coupling of an aromatic aldehyde and an
system of imidazo[1,2-a](di)azines which may increase
greatly the pharmacological profile.10 We reported re-
cently a highly effective method for the synthesis of
azacarboline and -aplysinopsin mimic structures from
heterocumulenes.11 We describe now the synthesis of
hydantoins 8, potential selective competitive NMDA
antagonists,12 via stereospecific ring-opening/ring-closure
of an azalactone obtained from an alumina-supported
heterocumulene.
appropriately substituted hydantoin. However, poor
yields, purification difficulties, and the formation of
mixtures of E and Z isomers are generally encountered.5
Such inconveniences have been circumvented by the
development of a tandem Staudinger/aza-Wittig reaction
followed by electrocyclic ring closure.6 Such methodology
allows the formation of nitrogenated heterocycles from
heterocumulenes which in turn are easily available from
iminophosphoranes. Using this route, an elegant syn-
thesis of several aplysinopsin-type alkaloids has been
accomplished by Molina and co-workers.7
Resu lts a n d Discu ssion
In the course of our studies on the reactivity of nitrogen
bridgehead azaindolizines, and in view of the pharma-
cological8 and theoretical9 interest of azaindole struc-
tures, we embarked on the development of a model
The 3-formyl derivative 3a 9 was condensed with ethyl
azidoacetate in the presence of sodium ethoxide at -30
°C to give azidovinyl 4a (νazido 2050 cm-1) in 78% yield.
Measurement of the long-range 13C-1H coupling constant
between the olefinic proton and the carbonyl carbon in
the coupled 13C NMR spectra proved to be diagnostic of
a (Z) arrangement.13 The preparation of iminophospho-
rane 5a was accomplished by Staudinger’s reaction of 4a
with triphenylphosphine in dichloromethane at room
temperature in 81% yield (Scheme 1). Spectral and
analytical data were consistent with the identity of
compound 5a and the (Z) configuration assignment
(3J H-Câ,CO ) 3.5 Hz).
* Author to whom correspondence should be addressed. Fax: (33)
04 73 27 77 27. E-mail: olivier.chavignon@u-clermont1.fr
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) (a) Clermont-Ferrand. (b) Tours. (c) Montpellier. (d) Barcelona.
(2) Kazlauskas, R.; Murphy, P. T.; Quinn, R. J .; Wells, R. J .
Tetrahedron. Lett. 1977, 61.
(3) Hollenbeak, K.; Schmitz, F. J . Lloydia 1977, 40, 479.
(4) Backer, J . T.; Wells, R. J . In Natural Products as Medicinal
Agents, Beal, J . L., Reinhard, E., Eds.; Hippokrates Verlag: Stuttgart,
1981; pp 299-303.
(5) (a) Ware, E. Chem. Rev. 1950, 46, 403. (b) Bateman, J . H. Kirk-
Othmer Encyclopedia of Chemical Technology; Wiley-Interscience: New
York, 1978; Vol. 12, p 692. (c) Djura, P.; Faulkner, D. J . J . Org. Chem.
1980, 45, 735. (d) Guella, G.; Mancini, I.; Zibrowins, H.; Pietra, F. Helv.
Chim. Acta 1988, 71, 773. (e) Guella, G.; Mancini, I.; Zibrowius, H.;
Pietra, F. Helv. Chim. Acta 1989, 72, 1444.
(6) Molina, P.; Vilaplana, M. J . Synthesis 1994, 1197.
(7) Molina, P.; Almendros, P.; Fresneda, P. M. Tetrahedron 1994,
50, 2241.
An aza-Wittig type reaction of iminophosphorane 5a
with aliphatic or aromatic isocyanates in dry toluene at
(10) (a) Chermann, J . C.; Gruest, J .; Montagnier, L.; Wendling, F.;
Tambourin, P.; Perrin, M.; Pochon, F.; Ducrocq, C.; Rivalle, C.; Bisagni,
E. C. R. Seances Acad. Sci., Ser. D 1977, 285, 945. (b) Marsais, F.;
Pineau, P.; Nivolliers, F.; Mallet, M.; Godard, A.; Quequiner, G. J . Org.
Chem. 1992, 57, 565.
(11) Chavignon, O.; Teulade, J . C.; Roche, D.; Madesclaire, M.;
Blache, Y.; Gueiffier, A.; Chabard, J . L.; Dauphin, G. J . Org. Chem.
1994, 59, 6413.
(12) (a) Hamilton, S. G.; Huang, Z.; Yang, X. J .; Patch, R. J .;
Narayanan, B. A.; Ferkany, J . W. J . Org. Chem. 1993, 58, 7263. (b)
Cordi, A.; Sun, E. US Patent 5, 252, 563.
(13) Vo¨geli, U.; Von Philipsborn, W.; Nagarajan, K.; Nair, M. D.
Helv. Chim. Acta 1978, 61, 607.
(8) Arbilla, S.; Allen, J .; Wick, A.; Langes, S. Eur. J . Pharmacol.
1986, 130, 257.
(9) (a) Hand, E. S.; Paudler, W. W. J . Org. Chem. 1975, 40, 2916.
(b) Teulade, J . C.; Gueiffier, A.; Viols, H.; Chapat, J . P.; Grassy, G.;
Perly, B.; Dauphin, G. J . Chem. Soc., Perkin Trans. 1 1989, 1895. (c)
Chavignon, O.; Teulade, J . C.; Madesclaire, M.; Gueiffier, A.; Blache,
Y.; Viols, H.; Chapat, J . P. J . Heterocycl. Chem. 1992, 29, 691. (d) Diez,
A.; Mavel, S.; Teulade, J . C.; Chavignon, O.; Sinibaldi, M. E.; Troin,
Y.; Rubiralta, M. Heterocycles 1993, 36, 2451.
S0022-3263(96)02174-3 CCC: $14.00 © 1997 American Chemical Society

4086 J . Org. Chem., Vol. 62, No. 12, 1997
Chezal et al.
Sch em e 1
F igu r e 2. ORTEP drawing of 8a ; the sizes of H atoms have
been reduced for clarity. Selected bond lengths (Å) and torsion
angles (deg) are as follows: N4-C8a, 1.390(3); C9-C1,
1.335(3); C1′-N2′, 1.387(3); C1′-C5′, 1.478(4); N4′-C5′,
1.363(2);
C3-N4-C8a-N1,
0.1(3);
N4-C3-C9-C1′,
Sch em e 2
-176.4(3); C3′-N4′-C5′-C1′, 1.1(3).
from the H and 13C NMR spectral data and confirmed
by the MS analysis (Experimental Section). The struc-
ture and the (Z) configuration of 8a were confirmed by
its crystallographic data.14 A projection of the molecule
obtained with the ORTEP program15 is given in Figure
2. The angle between the plane of the imidazopyridine
ring and the hydantoin group was 2.2°, which proves the
near planarity of the molecule. Bond distances and
angles and torsion angles were mostly those expected
from the hybridization of the atoms. The other angles
and bond distances were similar to those of other meth-
ylene hydantoins recently reported.16 The bond lengths
measured in the imidazopyridine system were consistent
with those of other compounds in the same series.17
Subsequent to the demonstration of the viability of the
intramolecular annulation described above, and in order
to further explore the synthetic potential of the alumina-
supported reaction, we pursued its application to the
imidazopyrimidine ring system. Thus, alumina-sup-
ported reaction of iminophosphorane 5b with isocyanates
yielded imidazolidindiones 8c,d in 49 and 45% yields,
respectively. The presence of an imidazolidindione func-
tionality at the imidazopyrimidine C-3 position was based
1
room temperature for 5-19 h gave the corresponding
carbodiimides 6a ,b, isolated as yellow plates. Since,
according to their usual behavior, indole carbodiimides
are expected to give the corresponding fused pyridine or
hydantoin annulation, our attention was turned to the
reactivity of 6a ,b. Surprisingly, when carbodiimides 6a ,b
were heated at 110 °C, and even when conditions were
forced (160 °C, o-Cl2C6H4), no evidence of the annulation
was observed. However, when a toluene solution of 6a
or 6b was heated at 110 °C for 3 h and the crude reaction
product was chromatographed on alumina (CH2Cl2-
MeOH, 98:2), azaaplysinopsins 8 were obtained together
with compounds 10 (8a :10a ) 98/2; 8b:10b ) 83/17).
Heterocumulenes 6a ,b were then refluxed in methanol
and yielded the corresponding imidazolones 10a ,b. The
structural assignment of compounds 10a ,b was proved
by the presence of a methoxy group signal in their 13C
NMR spectra. In contrast, when an alumina solid
support was impregnated with methylene chloride solu-
tions of heterocumulenes 6a ,b, followed by elution with
methanol, a rapid, stereospecific, and quantitative forma-
tion of (Z)-hydantoins 8a ,b was obtained (Scheme 2). No
reaction occurred when we performed the same experi-
ment on silica gel, probably due to its acidic character.
These experiments demonstrated that two different
mechanisms lead to compounds 8 and 10. In the first
case, heterocumulenes 6a ,b undergo a ring closure across
the ester functionality, followed by a spontaneous
Dimroth lactone-lactam rearrangement to give hydan-
toins 8a ,b. In the second case, the former heterocumu-
lenes would first be transformed into 2-methylisoureas
9a ,b which would lactamize to give imidazolones 10a ,b.
Interestingly, we noted a photoisomerization of 8a in
solution. Irradiation for 4 h at rt with 365 nm light of a
solution of neat (Z)-8a in (CD3)2SO was found to afford a
mixture appreciably richer in the (E)-8a isomer (E/Z >
75/25). The structural constitutions of 8a ,b were inferred
1
on the H and 13C NMR chemical shifts. This methodol-
ogy avoids the Dimroth rearrangement and the conse-
quent pyridinization which generally occurs in these
heterocyclic structures.11 The latter reaction is exempli-
fied by the formation of 11 due to thermal reaction of 5b
with C6H5NCO (Scheme 3).
In conclusion,we have described an alternative meth-
odology for obtaining the annulation of hydantoins, based
on an alumina-supported reaction of heterocumulenes.
A mechanistic explanation is given. The methodology
proves to be general for the preparation of azaaplysinop-
sins and has been applied here to the synthesis of
structures 8a -d .
(14) The authors have deposited atomic coordinates for this struc-
ture with the Cambridge Crystallographic Data Centre. The coordi-
nates can be obtained, on request, from the Director, Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ,
UK.
(15) (a) J ohnson, C. K. ORTEP-II: A Fortran Thermal Ellipsoid Plot
Program for Crystal Structure Illustrations, ORNL-5138, 1976. (b)
Main, P.; Fisker S. J .; Hull, S. E.; Lessinger, L.; Germain, G.; Declercq,
J . P.; Woolfson, M. M.; MULTAN 11/82. A System of Computer
Programs for the Automatic Solution of Crystal Structures from X-ray
Diffraction Data, University of York England and University of
Louvain, Belgium, 1980. (c) MolEN, An Interactive Structure Solution
Procedure, Enraf-NONIUS, Delft, The Netherlands, 1990. (d) Inter-
national Tables for X-ray Crystallography, Kynoch Press: Birmingham,
England; Vol. 4, 1974. (e) Crystal data for 8a with Mo KR radiation:
a ) 14.195(3), b ) 12.306(1), c ) 7.096(2), R (deg) ) 90, â (deg) ) 90,
γ (deg) )111.24(1), monoclinic, P21/b, 1505 observed reflections with I
> 3 σ(I). The final R factors were R ) 0.049 and RW ) 0.046.
(16) Gallucci, J .; Mathur, N.; Shechter, H. Acta Crystallogr., Sect.
C 1992, 48, 477.
(17) Teulade J . C.; Escale, R.; Rossi, J . C.; Chapat, J . P.; Grassy,
G.; Payard, M. Aust. J . Chem. 1982, 35, 1761.

Solid-Supported Heterocumulenes
J . Org. Chem., Vol. 62, No. 12, 1997 4087
alumina column. Elution with CH2Cl2 then with CH2Cl2/
methanol (80/20) afforded compound (Z)-5-[(imidazo[1,2-a]-
pyridin-3-yl)methylidene]-3-ethyl-1H-imidazolidine-2,4-di-
one (8a ) as yellow prisms (65%): mp > 260 °C; IR (KBr) 3120,
1730, 1670, 1640 cm-1; 1H NMR (DMSO-d6) δ 1.15 (t, 3H, J )
7 Hz), 3.52 (q, 2H, J ) 7 Hz), 6.99 (s, 1H), 7.08 (t, 1H, J ) 7
Hz), 7.42 (ps t, 1H), 7.68 (d, 1H, J ) 9 Hz), 8.37 (s, 1H), 8.87
(d, 1H, J ) 7 Hz), 10.55 (s, 1H); 13C NMR (DMSO-d6) δ 13.4,
32.9, 94.9, 113.3, 117.2, 119.2, 124.0, 125.2, 126.2, 135.9, 145.9,
154.5, 163.3; m/z (%): 256 (M+, 100), 157 (87); UV (MeOH):
353, 272, 224, 203 nm. Anal. Calcd for C13H12N4O2: C, 60.94;
H, 4.69; N, 21.87. Found: C, 61.05; H, 4.65; N, 21.92.
Sch em e 3
(E)-5-[(Im idazo[1,2-a ]pyr idin -3-yl)m eth yliden e]-3-eth yl-
1H-im id a zolid in e-2,4-d ion e (8a ). Irradiations under UV (λ
) 365 nm) of (Z)-8a (40 mg, 0.15 mmol) in (CD3)2SO were
carried out in a 5 mm NMR tube for 4 h, monitoring the
1
transformations by H and 13C NMR. Clean (Z)-8a f (E)-8a
isomerization was observed, without byproducts. The ratio of
the mixture was (E)/(Z) > 75/25; (E)isomer 1H NMR (DMSO-
d6) δ 1.15 (t, 3H, J ) 7 Hz), 3.52 (q, 2H, J ) 7 Hz), 6.71 (s,
1H), 7.05 (ps t, J ) 6 Hz, 1H), 7.37 (ps t, 1H), 7.65 (d, 1H, J )
9 Hz), 8.50 (d, 1H, J ) 7 Hz), 8.75 (s, 1H), 10.50 (s, 1H); 13C
NMR (DMSO-d6) δ 13.3, 32.7, 99.5, 113.29, 117.3, 119.2, 124.0,
125.2, 126.2, 137.4, 145.8, 152.8, 161.7; m/z (%): 256 (M+, 100),
157 (87).
5-(Im id a zo[1,2-a ]p yr id in -3-yl]m eth ylid en e)-3-eth yl-2-
m eth oxyim id a zolin -4-on e (10a ). A solution of 6a (0.46
mmol) in methanol (40 mL) was heated at reflux for 4 h. After
cooling, the solvent was removed off under reduced pressure,
and the residue was chromatographed on an alumina column
with CH2Cl2 as eluent to give the imidazoline 10a as yellow
Exp er im en ta l Section 18
P r ep a r a tion of Eth yl r-Azid o-â-(im id a zo[1,2-a ]p yr i-
d in -3-yl)p r op en oa te (4a ). Ethyl azidoacetate (10.38 g, 80
mmol) was added dropwise at -30 °C to a stirred solution
containing sodium (0.8 g, 35 mmol) in dry ethanol (25 mL).
To this solution was added dropwise a mixture of aldehyde (8
mmol) in dry ethanol (10 mL). The reaction mixture was
returned to rt and stirred for 3 h. The solution was poured
into aqueous saturated NH4Cl solution (100 mL) and then
extracted with ether. The organic layers were dried over
anhydrous Na2SO4 and evaporated in vacuo. The crude
product was chromatographed on an alumina column eluting
with CH2Cl2 to give 4a (78%): mp 98-100 °C; IR (KBr) 2050,
prisms (27%); mp 180-182 °C; IR (KBr) 1700, 1640, 1260 cm-1
;
1
1680, 1220 cm-1; H NMR (CDCl3) δ 1.35 (t, 3H, J ) 7 Hz),
1H NMR (CDCl3) δ 1.25 (t, 3H, J ) 7 Hz), 3.61 (q, 2H, J ) 7
Hz), 4.20 (s, 3H), 6.95 (t, 1H, J ) 7 Hz), 7.11 (s, 1H), 7.28 (ps
t, 1H), 7.69 (d, 1H, J ) 9 Hz), 8.42 (d, 1H), 8.61 (s, 1H); 13C
NMR (CDCl3) δ 7.8, 30.2, 54.4, 108.5, 117.2, 122.3, 126.0, 128.7,
130.9, 141.3, 146.2, 153.7, 17O.8, 177.3; m/z (%): 270 (M+, 57),
156 (100), 58 (83). Anal. Calcd for C14H14N4O2: C, 62.22; H,
5.19; N, 20.74. Found: C, 61.98; H, 5.20; N, 20.79.
4.31 (q, 2H, J ) 7 Hz), 6.87 (t, 1H, J ) 7 Hz), 6.96 (s, 1H),
7.21 (ps t, 1H), 7.57 (d, 1H, J ) 9 Hz), 8.11 (d, 1H), 8.38 (s,
1H); 13C NMR (CDCl3) δ 14.1, 62.1, 108.5, 113.4, 118.0, 119.7,
122.3, 123.1, 125.9, 138.7, 146.4, 162.8. Anal. Calcd for
C12H11N5O2: C, 56.03; H, 4.28; N, 27.24. Found: C, 56.19; H,
4.29; N, 27.21.
Eth yl r-[(Tr ip h en ylp h osp h or a n ylid en e)a m in o]-â-(im i-
d a zo[1,2-a ]p yr id in -3-yl)p r op en oa te (5a ). To a solution of
vinylazide (6 mmol) in dry CH2Cl2 (20 mL) was added
dropwise, at 0 °C, a solution of triphenylphosphine (1.57 g, 6
mmol) in the same solvent (20 mL). The reaction mixture was
stirred at rt for 12 h, and the solvent was removed in vacuo.
The crude product was purified by chromatography on alumina
column, eluting with CH2Cl2 to give the iminophosphorane 5a
A solution of carbodiimide 6a or 6b in toluene was heated
at 110 °C for 3 h. After cooling, the residue was chromato-
graphed on an alumina column, eluting with CH2Cl2-MeOH
(98:2) to give the imidazolines 10a ,b and then the hydantoins
8a ,b. The ratios were 8a /10a : 98/2 and 8b/10b: 83/17.
Th er m al Reaction of Im in oph osph or an e 5b with P h en -
yl Isocya n a te. To a solution of iminophosphorane 5b (2
mmol) in 25 mL of 1,2,4-trichlorobenzene was added phenyl
isocyanate (2.2 mmol). The reaction mixture was stirred at
room temperature for 3 h and then at 160 °C for 8 h. After
cooling, the solution was washed with cold ethanol to remove
phosphine oxide, and the resulting mixture was chromato-
graphed on an alumina column eluting with CH2Cl2 to yield
product 11 as yellow prisms (0.49 g, 72%): mp > 260 °C; IR
(81%): mp 164-166 °C; IR (KBr) 1690, 1580, 1425, 1225 cm-1
;
1H NMR (CDCl3) δ 0.98 (t, 3H, J ) 7 Hz), 3.88 (q, 2H, J ) 7
Hz), 6.83 (t, 1H, J ) 7 Hz), 6.96 (d, 1H, 4J H-P ) 7 Hz), 7.15 (ps
t, 1H), 7.47 (m, 9H), 7.61 (d, 1H, J ) 9 Hz), 7.74 (m, 6H), 8.20
(d, 1H, J ) 7 Hz), 8.59 (s, 1H); 13C NMR (CDCl3) δ 14.1, 60.8,
101.9 (d, 3J P-C ) 21 Hz), 111.9, 117.8, 123.5, 123.7, 124.1, 128.3
3
2
(d, J P-C ) 12 Hz, 3C), 131.1, 132.3 (d, J P-C ) 10 Hz, 6C),
1
(KBr) 3400, 1730, 1250 cm-1; H NMR (CDCl3) δ 1.54 (t, 3H,
1
2
132.6 (d, J P-C ) 103 Hz, 3C), 135.34(d, J P-C ) 6 Hz), 135.6,
144.9, 166.8 (d, 3J P-C ) 7 Hz); m/z (%): 491 (M+, 42), 156 (100).
Anal. Calcd for C30H26N3O2P: C, 73.32; H, 5.30; N, 8.55.
Found: C, 73.35; H, 5.28; N, 8.58.
J ) 7 Hz), 4.51 (q, 2H, J ) 7 Hz), 7.11 (m, 2H), 7.42 (t, 2H),
8.07 (s, 1H), 8.12 (d, 2H), 8.21 (s, 1H), 8.78 (dd, 1H, J ) 7 Hz,
J ) 2 Hz), 8.91 (dd, 1H, J ) 4 Hz); 13C NMR (CDCl3) δ 14.4,
61.7, 100.9, 108.8, 118.5, 122.4, 129.1, 130.1, 131.4, 133.8,
138.6, 140.0, 147.7, 150.6, 156.4, 165.9; m/z (%): 333 (M+, 94),
260 (78), 79 (100). Anal. Calcd for C18H15N5O2: C, 64.86; H,
4.50; N, 21.02. Found: C, 65.05; H, 4.49; N, 21.04.
P r ep a r a tion of Ca r bod iim id e 6b. To a solution of
iminophosphorane (0.81 mmol) in dry toluene (50 mL) was
added dropwise at 0 °C phenyl isocyanate (1.68 mmol). The
solution was stirred at 0 °C for 30 min and then at rt for 5 h.
The solvent was removed off under reduced pressure, and the
crude product was washed with hexane to remove phosphine
oxide and give 6b (56%): mp: 164-166 °C; IR (KBr) 2130,
Ackn owledgm en t. We express our grateful acknowl-
edgment to Claire Lartigue for mass spectral data and
Mr. Damien Canitrot and Henri Viols for skillful
experimental work. We thank the University of Au-
vergne for financial support.
1
1690, 1240 cm-1; H NMR (CDCl3) δ 1.39 (t, 3H, J ) 7 Hz),
4.41 (q, 2H, J ) 7 Hz), 6.96 (t, 1H, J ) 7 Hz), 7.16 (m, 1H),
7.30 (m, 6H), 7.67 (d, 1H, J ) 9 Hz), 8.22 (d, 1H), 8.65 (s, 1H);
13C NMR (CDCl3) δ 14.3, 62.3, 112.1, 113.5, 118.3, 120.5, 122.6,
123.3, 124.4 (2C), 125.4, 126.0, 129.4 (2C), 135.1, 138.0, 139.1,
146.7, 164.0; m/z (%): 332 (M+, 34), 156 (100), 78 (50). Anal.
Calcd for C19H16N4O2: C, 68.67; H, 4.82; N, 16.87. Found: C,
68.83; H, 4.81; N, 16.88.
Su p p or tin g In for m a tion Ava ila ble: Experimental data
for 4b, 5b, 6a ,d , 8b-d , and 10b, and crystal data for 8a (3
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
Gen er a l P r oced u r e for th e P r ep a r a tion of Im id a zoli-
d in e-2,4-d ion e 8a . The carbodiimide was poured onto an
(18) For general experimental details, consult ref 11.
J O962174Y