Reactivity of indanedioneketene dimer with amines

Article abstract of DOI:10.1021/jo061879p

The highly reactive indanedioneketene 5, resulting from the thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone, 4), in the absence of nucleophiles dimerizes to the corresponding tetraoxo spiro oxetanone 6 in quantitativ

Full text of DOI:10.1021/jo061879p

Reactivity of Indanedioneketene Dimer with Amines
Elizabeth Malamidou-Xenikaki,*,† Spyros Spyroudis,† Maria Tsanakopoulou,†
and Harald Krautscheid‡
Department of Chemistry, Aristotle UniVersity of Thessaloniki, 54124 Thessaloniki, Greece,
and Institute of Inorganic Chemistry, UniVersity of Leipzig, D-04103 Leipzig, Germany
malamido@chem.auth.gr
ReceiVed September 12, 2006
The highly reactive indanedioneketene 5, resulting from the thermal decomposition of phenyliodonium
ylide of 2-hydroxy-1,4-naphthoquinone (lawsone, 4), in the absence of nucleophiles dimerizes to the
corresponding tetraoxo spiro oxetanone 6 in quantitative yield. This oxetanone exhibits an interesting
reactivity toward amines.
SCHEME 1
Introduction
Zwitterionic iodonium compounds (ZIC) play an important
role in the chemistry of hypervalent iodine. These compounds
exhibit a diverse reactivity depending mainly on the nature of
the anionic counterpart of the aryliodonio moiety. Among ZIC
phenyliodonium ylides of 2-hydroxyquinones 1 have attracted
our attention mainly for two reasons: Their interesting reactivity
and the fact that a great number of 2-hydroxyquinones are found
in nature and their majority exhibit some kind of biological
activity.1
Two distinguished modes of reactivity of the above-mentioned
ylides exist: The replacement of the labile phenyliodonio moiety
by another functional group to afford 2 and the thermal
degradation of ylides to the very reactive R,R′-dioxoketenes 3
(Scheme 1).
taking place either under photochemical conditions2 or under
metal catalysis. Sonogashira,3a Stille,3b,c and Suzuki3d coupling
reactions take place under palladium catalysis, whereas substitu-
tion of the phenyliodonio group by functionalized indoles is
effected by catalytic amounts of copper triflate.4
Regarding the second reaction mode, the interesting issue
from a synthetic point of view is the formation of cyclopen-
tenediones. In refluxing acetonitrile, dioxoketenes 3 afford
substituted cyclopentenediones through reaction with water
present in the solvent and spontaneous decarboxylation of the
intermediary acid.5 This thermal degradation of ylides 1 offers
an effective access to these interesting dienophiles, which can
be used further for the construction of more complicated
structures.6
In the first reaction mode, the hydroxyquinone frame is
retained leading to a variety of substituted hydroxyquinones.
Especially noteworthy are the C-C bond forming reactions
† Aristotle University of Thessaloniki.
‡ University of Leipzig.
(1) (a) Thomson, R. H. Naturally Occurring Quinones IV; Blackie
Academic & Professional: London, UK, 1997. (b). Spyroudis, S. Molecules
2000, 5, 1291.
(2) Hatzigrigoriou, E.; Spyroudis, S.; Varvoglis, A. Liebigs Ann. Chem.
1989, 167.
(3) (a) Kobayashi, K.; Uneda, T.; Kawakita, M.; Morikawa, O.; Konishi,
H. Tetrahedron Lett. 1997, 38, 837. (b) Stagliano, K. W.; Malinakova,
H. C. J. Org. Chem. 1999, 64, 8034. (c) Emadi, A.; Harwood, J. S.;
Kohanim, S.; Stagliano, K. W. Org. Lett. 2002, 4, 521. (d) Kazantzi, G.;
Malamidou-Xenikaki, E.; Spyroudis, S. Synlett 2006, 2597.
(4) Koulouri, S.; Malamidou-Xenikaki, E.; Spyroudis, S.; Tsanakopoulou,
M. J. Org. Chem. 2005, 70, 5627.
(5) Papoutsis, I.; Spyroudis, S.; Varvoglis, A. Tetrahedron Lett. 1994,
35, 8449.
(6) (a) Spyroudis, S.; Xanthopoulou, N. J. Org. Chem. 2002, 67, 4612.
(b) Spyroudis, S.; Xanthopoulou, N. ARKIVOC 2003, 6, 95. (c) Mehta, G.;
Singh, S. R. Tetrahedron Lett. 2005, 46, 2079. (d) Mehta, G.; Singh, S. R.
Angew. Chem., Int. Ed. 2006, 45, 2079.
10.1021/jo061879p CCC: $37.00 © 2007 American Chemical Society
Published on Web 12/14/2006
502
J. Org. Chem. 2007, 72, 502-508

ReactiVity of Indanedioneketene Dimer with Amines
SCHEME 2
FIGURE 1. Shielding of 4-H by the aryl group.
SCHEME 4
SCHEME 3
SCHEME 5
for prolonged periods without apparent decomposition. Exposed
in air it turns reddish as it is transformed to red-colored
dihydroxyquinone 9, obviously by humidity. It must be noted
that this type of [2+2] dimerization to oxetanone 6 is rather
unusual, as other R-oxoketenes also dimerize but mainly in
[4+2] cycloaddition mode.7
Oxetanone 6 reacts easily with primary aromatic amines 7.
Upon addition of 2 equiv of amine to stirred suspensions of
compound 6 in dichloromethane two products were obtained
from the reaction mixture in high yields: The yellow imino-
amides 8, isolated by column chromatography, and the red 2,3-
dihydroxy-1,4-naphthoquinone (9), crystallized from the reaction
solution, as illustrated in Scheme 3.
Dioxoketenes analogous to 3 are very reactive and only a
few are reported in the literature.7 Dioxoketene 5, resulting from
the phenyliodonium ylide of lawsone (4) in refluxing dichloro-
methane, reacts smoothly with aromatic amines to afford amides
existing in solution in a most unusual enol form.8 The same
type of reactivity was observed with other amino compounds
such as amino acids and their esters, aminophenols, amino-
alcohols, and ureas,9 as well as with C-nucleophiles such as
indoles and enamines.4 In the absence of nucleophiles, dioxo-
ketene 5 dimerizes to oxetanone 6 (Scheme 2).4 The latter
proved to be a reactive and interesting molecule and we wish
to report the results of its reaction with amines.
It is interesting to note that in the 1H NMR spectra of
iminoamides 8 a strong shielding effect is observed for the
aromatic proton of the fused benzene ring next to the imino
group (4-H). Indeed this proton, normally resonating at δ ∼7.80,
appears as a doublet at δ 6.55-6.12. This upfield shift can be
explained by a Z to the fused benzene ring configuration of the
imino group, caused by the formation of a hydrogen bond
between the nitrogen of the imino group and the enolic hydrogen
of the amide moiety, and by the restricted rotation of the aryl
ring, as shown in Figure 1.
Results and Discussion
Oxetanone 6 was prepared by refluxing dispersions of ylide
4 in dichloromethane and isolated as yellow crystals by
crystallization from the resulting clear solution, as described in
a previous publication.4 By careful and thorough treatment of
the reaction solution, yield can reach 95-98%, if ylide 4 is
used in a scale of 3-4 mmol. Oxetanone 6 is fairly stable and
can be stored in the refrigerator, with exclusion of moisture,
The shielding is gradually increasing from para-substituted
(δ 6.45-6.55) to ortho-substituted (δ 6.29) and to ortho,ortho-
disubstituted aryl compounds (δ 6.18-6.12), due possibly to
the increasing hindrance of rotation of the aryl ring.
Upon addition of 1 equiv of primary aromatic amine 7 to a
dispersion of oxetanone 6 in CH2Cl2 the iminoesters 10a-i were
isolated in good yields by crystallization from the reaction
solution, usually accompanied by small amounts (13-20%) of
(7) (a) Wentrup, C.; Heilmayer, W.; Kollenz, G. Synthesis 1994, 1219.
(b) Stadler, A.; Zangger, K.; Belaj, F.; Kollenz, G. Tetrahedron 2001, 6757.
(c) Wallfisch, B. C.; Belaj, F.; Wentrup, C.; Kappe, C. O.; Kollenz, G.
J. Chem. Soc., Perkin Trans. I 2002, 599. (d) Tidwell, T. T. Ketenes; John
Wiley & Sons: Hoboken, NJ, 2006.
(8) Malamidou-Xenikaki, E.; Spyroudis, S.; Tsanakopoulou, M. J. Org.
Chem. 2003, 68, 5627.
(9) Spagou, K.; Malamidou-Xenikaki, E.; Spyroudis, S. Molecules 2005,
10, 226.
J. Org. Chem, Vol. 72, No. 2, 2007 503

Malamidou-Xenikaki et al.
SCHEME 6
FIGURE 2. Ellipsoid drawing (50% probability) of 12a.
iminoamides 8 and dihydroxyquinone 9 (Scheme 4). If a second
equivalent of amine 7a was added to a suspension of isolated
10a the reaction proceeded further to afford 8a and 9, proving
thus that the reaction proceeds indeed in two steps. Again an
upfield shift (δ 6.48-5.95) of the 4-H of the fused benzene
ring is observed in iminoesters 10, analogous to the Z config-
uration of the aryl ring of compounds 8, due to internal hydrogen
bond formation. Compounds 10 represent the first step of the
reaction of oxetanone 6 with primary aromatic amines. Interest-
ingly enough, the nucleophilic attack of the amine takes place
on one of the carbonyls of the spiro-cyclopentenedione ring,
and not on the oxetanone ring, with a simultaneous expansion
of the second cyclopentenedione ring to the hydroxynaphtho-
quinone moiety.
To clarify the reactivity pattern of oxetanone 6, its reaction
with secondary amines, three aromatic 11a-c and one nonaro-
matic 11d, was then investigated. In this case the reaction
proceeded smoothly under the previously described conditions
but the only isolable products were the enaminoesters 12a-d,
either with 1 or 2 equiv of amine (Scheme 5). Compounds 12
resisted attack of a second amine molecule even if this attack
was attempted on dispersions of 12 in refluxing dimethoxy-
ethane. This difference in reactivity between imino- and
enaminoesters 10 and 12 verifies the proposed structures, as
will be discussed in detail.
The shielding effect of the phenyl group on the 4-H of the
fused benzene ring is greater in compounds 12a-c than that in
the corresponding compounds 10. This proton appears as a
doublet at δ 5.60-5.70, a resonance value most unusual for
aromatic protons, analogous to the conformation of the aryl ring
of compounds 10. X-ray structure determination of derivative
12a verified this observation as is illustrated in Figure 2. The
phenyl ring is almost perpendicular (84.5° tilt) to the ring system
of C-12 to C-20 and hence the strong shielding effect of the
hydrogen connected to C-17. This favorable less hindered
conformation can be attributed to restricted rotation of the
C-N(R′)Ph bond. As regards the greater shielding effect of the
certain hydrogen, compared to the corresponding hydrogen in
the iminoesters 10, it can be explained in terms of the greater
bulkiness of the R′ group in 12a-c compared to that of the
hydrogen in 10. This bulkiness, combined with the lack of
hydrogen bond developed between NH and CO in 10, brings
the phenyl group closer to the proton of C-17 and hence the
upfield shift of the latter. It must be noted that this shielding
effect is not observed in derivative 12d, since in this compound
the phenyl group is not directly attached to nitrogen and lies a
greater distance from the proton that would be shielded.
This structure elucidation verifies the assumption that this
ring expansion, from benzocyclopentenedione to naphtho-
quinone, takes place immediately after the first attack of the
amine to the carbonyl of the spiro-cyclopentenedione ring of
oxetanone 6.
Finally, the reaction of the primary nonaromatic amines
13a-c with oxetanone 6 was investigated and the results are
shown in Scheme 6.
The reaction of oxetanone 6 with 1 equiv of amine 13
afforded the iminoesters 14a-c, as in the case of primary
aromatic amines. These compounds were isolated in high yields
by crystallization from the reaction solution and exhibit no
shielding of the 4-H of the fused benzene ring. Either by addition
of 2 equiv of amine 13 in the initial reaction mixture or of 1
equiv in dispersions of pure isolated 14a-c in dichloromethane,
addition compounds 16a-c were isolated in high yields. These
compounds presumably arise from the Michael addition of
amine to the enone system of 14a-c to afford initially 15a-c,
which tautomerize to 16a-c. Spectroscopic data strongly
indicate that indeed these compounds exist in solution in the
tautomeric form 16a-c. Addition compounds 16a-c are fairly
stable even in refluxing dichloromethane. They are converted
504 J. Org. Chem., Vol. 72, No. 2, 2007

ReactiVity of Indanedioneketene Dimer with Amines
SCHEME 7
SCHEME 8
to the final iminoamides 17a-c and 2,3-dihydroxy-1,4-naph-
thoquinone (9) only after heating in refluxing dimethoxyethane.
These iminoamides exist also in an enol-amide form, analogous
to that of compounds 8, but no shielding effect for the
corresponding 4-H is observed in 1H NMR spectra. It is obvious
that in this case there is no restriction in the rotation of the
phenyl (or furyl) group due to its greater distance from the fused
benzene ring.
SCHEME 9
It is most likely that compounds analogous to 16a-c (or to
their tautomers 15a-c) are intermediates in the reaction of 6
with primary aromatic amines, although they have never been
isolated or detected. In that case, the reaction proceeds
spontaneously to afford the final iminoamides 8.
Finally, upon refluxing of the isolated intermediates 15 u 16
in dimethoxyethane, the iminoamides 17 and hydroxyquinone
9 are formed, whereas the corresponding iminoamides 8 (R )
Ar) and compound 9 are obtained spontaneously without
isolation of intermediates analogous to 15 or 16. This difference
in stability can be attributed to the different basicity of aromatic
and nonaromatic primary amines.
To verify that the difference in reactivity between enamino-
and iminoesters 12 and 10 toward amines is the result of the
enolic structure of the latter, the reaction of a representative
derivative of both classes with a secondary amine was inves-
tigated. Whereas the reaction of enaminoester 12a with N-
methylaniline (11a) does not proceed at all, even in refluxing
dimethoxyethane as was already mentioned (Scheme 9), the
corresponding reaction of iminoester 10a afforded the mixed
iminoamide 22 and dihydroxyquinone 9 at room temperature
(Scheme 10). This is a strong indication that indeed esters 10
exist in the enolic imino form and that the Michael-type addition
of amine takes place at their enone moiety.
On the basis of all these findings the pathway for the reaction
of oxetanone 6 with amines can be outlined. The reaction starts
with nucleophilic attack of the amine to one of the carbonyls
of the spiro-cyclopentenedione moiety to form 18, which gives
the iminium intermediate 19. The latter initiates a skeletal
rearrangement, which through ring expansion and attack of the
hydroxy anion to the ethylenic carbon of the indanedione moiety
leads to the enamino ester 12, as shown in Scheme 7. In the
case of secondary amines (R′ * H) these compounds cannot
react further with excess amine, as was already mentioned, and
these compounds are isolated in the enaminoester form 12. In
the case of primary amines (R′ ) H), a tautomerization takes
place and these compounds are isolated in the form of
iminoesters 10 and 14, for aromatic and nonaromatic amines,
respectively.
Whereas enaminoesters 12 do not react further with amine,
the presence of the enone moiety in iminoesters 10 and 14
facilitates a Michael-type addition of the second equivalent of
amine to afford 20, which can tautomerize to 21 (Scheme 8).
In the case of primary nonaromatic amines (R ) CH2R′′), the
intermediate 20 u 21 is stable and can be isolated (15 u 16).
The observation that enaminoesters 12 cannot react further
with secondary amines has an exception: From the reaction of
12a with diethylamine at room temperature the addition product
J. Org. Chem, Vol. 72, No. 2, 2007 505

Malamidou-Xenikaki et al.
SCHEME 10
FIGURE 3. General structure of compounds 8, 10, and 14.
SCHEME 12
SCHEME 11
23, analogous to 16, was isolated. In this case it is most likely
that diethylamine, being a stronger nucleophile, is able to attack
the carbonyl of an enaminoester leading to the isolation of 23
(Scheme 11).
Moreover, the reaction of oxetanone 6 with 1 or 2 equiv of
diethylamine afforded the enaminoester 24 and the addition
product 25, respectively. The latter is most stable and only after
prolonged heating in dimethoxyethane afforded the enamine of
indanedione 28 in moderate yield (Scheme 12). This compound
presumably arises from the decarboxylation of the intermedi-
ate acid 27, a hydrolysis product of the corresponding
diethylamide 26.
Spectroscopic data also support the suggested structures. In
the IR spectrum, enaminoesters 12 exhibit carbonyl absorption
at 1720-1740 cm-1, indicating the presence of an ester group.
This absorption is missing in the cases of compounds 10 and
14, where the highest absorptions in the carbonyl region appear
at 1660-1675 cm-1, suggesting that these compounds exist in
the enol form A and not in the ester form B in Figure 3 (X )
O, R ) Ar for 10; X ) O, R ) CH2R′′ for 14).
compounds are highly insoluble. Iminoesters 10, although stable
in the solid state, start to decompose after some time in the
NMR solvent (CDCl3 + DMSO-d6) and therefore clear spectra,
at least for the tertiary carbons, cannot always be obtained. Other
characteristic peaks in their 13C NMR spectra are those at δ
189-190 for C-4, δ 169-170 for C-1, and δ 165-166 for C-3
(Figure 3).
Although spectroscopic data indicate that the imino form is
the predominant one for compounds 8a-i and 10a-i in solution,
X-ray crystal structure determination of 8b revealed that it is
crystallized in the enamino form presented in Figure 4.
Again two internal hydrogen bonds account for the stability
of the molecule but the tilt (48.8°) of the o-tolyl ring does not
justify well the shielding of the proton connected to C-5 (δ 6.29)
as is clearly shown from a different view of the same structure.
This is another indication that indeed in solution the predominant
structure is the imino one accounting better for the observed
upfield shift of the corresponding proton.
1
This enolic proton in H NMR resonates at δ 10.60-10.90
(in CDCl3 + DMSO-d6) for 10 and 14, whereas the hydrogen
of the hydroxy group in the quinone ring is usually not
observable. The corresponding enol proton in iminoamides 8
(A, X ) NH, R ) Ar) and 17 (A, X ) NH, R ) CH2R′′)
appears as a broad singlet at δ 11.30-12.30 (in CDCl3) and a
second broad singlet at δ 9.50-10.90 is assigned to N-H.
In 13C NMR a very characteristic and indicative peak for all
compounds having the imino-enol structure A is that of a tertiary
carbon at δ 97-99, which is assigned to C-2 (A in Figure 3).
In the case of iminoesters 10 this peak, as well as other peaks
for tertiary carbons, is hardly seen and the reason is the
prolonged time needed to obtain a 13C NMR spectrum, as these
In conclusion, oxetanone 6, obtained most conveniently from
the thermal transformation of phenyliodonium ylide 4 and
possessing an unusual tetraoxo spiro structure, exhibits an
506 J. Org. Chem., Vol. 72, No. 2, 2007

ReactiVity of Indanedioneketene Dimer with Amines
mmol) in CH2Cl2 (4 mL) and stirring was continued overnight. The
red crystals of dihydroxynaphthoquinone 9 (yields 80-85%) were
filtered off and the filtrate was concentrated and chromatographed
on column (silica gel, hexanes-ethyl acetate 3:1) to afford the
iminoamides 8a-i. The isolated derivatives 8a-i were pure enough
but analytical samples were obtained by recrystallization from CH2-
Cl2-hexanes. For simplicity reasons compounds 8a-i are named
according to their amide tautomeric form (e.g., compound 8a in
its enol-amide form should be named (2E, 3E)-2-{hydroxy[(4-
methylphenyl)amino]methylene}-3-[(4-methylphenyl)imino]indan-
1-one).
Quinone 9 was also prepared following a reported method10 and
its spectra were in all respects identical with the ones reported in
the literature.11
B. Reaction with 1 equiv of Amine. A solution of the aromatic
amine 7a-i (0.3 mmol) in CH2Cl2 (3 mL) was added to a stirring
suspension of oxetanone 6 (0.3 mmol) in CH2Cl2 (4 mL) and stirring
was continued until a clear orange-colored solution resulted (30-
60 min), except in the cases of the para-substituted anilines 7a, 7c,
and 7g where the reactions were completed almost immediately.
By addition of hexanes (∼10 mL) to the reaction mixture imi-
noesters 10a-i were precipitated and isolated by filtration. The
yellow solids were washed repeatedly with a mixture of hexanes-
dichloromethane (3:1) and were pure enough. No further purification
was possible due to their tendency to decompose upon attempted
recrystallization. The fitrate was concentrated and subjected to
column chromatography (silica gel, hexanes-ethyl acetate 3:1) to
afford the iminoamides 8a-i in yields ranging from 13% to 20%.
The other product of the reaction, dihydroxyquinone 9, was detected
by TLC but it could not be isolated by either crystallization or
column chromatography.
The reaction of 6 with 2 equiv of primary amine 7a was also
repeated in two steps: The iminoester 10a (0.1 mmol), isolated
with the addition of the corresponding amine 7a as described above,
was dispersed in CH2Cl2 (4 mL) and 0.1 mmol of the same amine
was added under stirring. The procedure was continued as in the
case of reaction of 6 with 2 equiv of amine to afford iminoamide
8a and hydroxyquinone 9 in 80% yield.
General Procedure for the Reaction of Oxetanone 6 with
Secondary Amines 11a-d. A solution of the secondary amine
11a-d (0.3 mmol) in CH2Cl2 (3 mL) was added to a stirring
suspension of oxetanone 6 (0.3 mmol) in CH2Cl2 (4 mL) and stirring
was continued until a clear orange-colored solution resulted (15-
60 min). By gradual addition of hexanes (∼10 mL) to the reaction
mixture enaminoesters 12a-d were precipitated and isolated by
filtration. The orange-yellow solids were washed repeatedly with
a mixture of hexanes-dichloromethane (3:1) and recrystallized from
dichloromethane-hexanes.
FIGURE 4. Two views of the ellipsoid drawing (35% probability)
of 8b.
interesting reactivity toward amines. Although the reaction path,
involving as a first step the attack of amine to the carbonyl of
the spiro-cyclopentenedione moiety, is the same for all amines,
stability and isolation of intermediary products depends mainly
on the nature of the amine. This study has shown that oxetanone
6 (as well as analogous oxetanones possibly accessible in the
same way from other aryliodonium ylides) has the potential to
be an interesting building block in organic synthesis. For this
reason the investigation of its reactivity with other types of
nucleophiles is now in progress.
General Procedure for the Reaction of Oxetanone 6 with
Primary Nonaromatic Amines 13a-c. The same procedure
described above for secondary amines was followed.
Reaction of Compounds 14a-c with Amines 13a-c. A
solution of the amine 13a-c (0.1 mmol) in CH2Cl2 (2 mL) was
added to a stirring suspension of compound 14a-c (0.1 mmol) in
CH2Cl2 (2 mL) and stirring was continued until a clear red-orange
solution resulted (15-60 min). By addition of hexanes (3-4 mL)
to the reaction mixture the addition compounds 16a-c were
precipitated and isolated by filtration. The red-orange solids were
washed repeatedly with a mixture of hexanes-dichloromethane
(3:1).
Experimental Section
Indanedioneketene dimer, 4′-(1,3-dioxo-1,3-dihydro-2H-inden-
2-ylidene)spiro[indene-2,3′-oxetane]-1,2′,3-trione (6), was pre-
pared as described in a previous publication.4 Yields up to 95-
98% can be obtained if a scale of 3-4 mmol of ylide 4 in 30-40
mL of dry CH2Cl2 is used.
Thermal Transformation of Addition Compounds 16a-c to
Iminoamides 17a-c. Dispersions of addition compounds 16a-c
(0.2 mmol) in DME (3 mL) were refluxed for 2 h. The resulting
red solution was concentrated to dryness, CH2Cl2 (3 mL) was added,
and the red crystals of dihydroxyquinone 9 were filtered off. The
General Procedure for the Reaction of Oxetanone 6 with
Primary Aromatic Amines 7a-i. A. Reaction with 2 equiv of
Amine. A solution of the aromatic amine 7a-i (0.6 mmol) in CH2-
Cl2 (3 mL) was added to a stirred suspension of oxetanone 6 (0.3
(10) Fieser, L. F.; Gates, M. D. J. Am. Chem. Soc. 1941, 63, 2948.
(11) Khandagale, P.; Chikate, R.; Joshi, S. B.; Kulkarni, B. A. J. Alloys
Compds. 2005, 392, 112.
J. Org. Chem, Vol. 72, No. 2, 2007 507

Malamidou-Xenikaki et al.
1
filtrate was concentrated and chromatographed on column (silica
gel, hexanes-ethyl acetate 3:1) to afford the iminoamides 17a-c.
The isolated derivatives 17a-c were pure enough but analytical
samples were obtained by recrystallization from CH2Cl2-hexanes.
Compounds 16a-c and 17a-c were also obtained from the
reaction of oxetanone 6 with excess amounts (2.5-3.0 mmol) of
the corresponding amines 13a-c in 62-65% and 16-18% yields,
respectively.
Reaction of 10a with N-Methylaniline (11a). A solution of
N-methylaniline (11a) (0.3 mmol) in CH2Cl2 (3 mL) was added to
a stirring suspension of iminoester 10a (0.3 mmol) in CH2Cl2 (4
mL) and stirring was continued overnight. The precipitated dihy-
droxyquinone 9 was filtered off and the concentrated filtrate was
subjected to column chromatography to afford N-methyl-3-
[(4-methylphenyl)amino]-1-oxo-N-phenyl-1H-indene-2-carbox-
amide (22). Yield 80%: mp 142-145 °C; IR (KBr) 1617, 1610
cm-1; 1H NMR (CDCl3, 300 MHz) δ 11.30 (br s, 1H), 7.38-7.25
(m, 10H), 7.18 (t, J ) 6.9 Hz, 1H), 7.06 (t, J ) 7.6 Hz, 1H), 6.46
(d, J ) 7.8 Hz, 1H), 3.48 (s, 3H), 2.45 (s, 3H); 13C NMR (CDCl3,
75 MHz) δ 185.5, 169.2, 168.3, 145.7, 138.2, 136.0, 135.0, 134.7,
132.0, 130.8, 130.1, 128.8, 126.3, 125.9, 125.8, 123.2, 121.6, 100.4,
38.7, 21.2; EI-MS m/z (%) 368 (M+, 7), 261 (100), 107 (78). Anal.
Calcd for C24H20N2O2: C, 78.24; H, 5.47; N, 7.60. Found: C, 77.89;
H, 5.81; N, 7.90.
Reaction of 12a with Diethylamine. The reaction under the
previously described conditions was completed in a few minutes.
Addition of hexanes to the reaction mixture afforded 2-[(diethyl-
amino)(hydroxy){3-[methyl(phenyl)amino]-1-oxo-1H-inden-2-
yl}methoxy]-3-hydroxynaphthoquinone (23). Yield 88%: mp
146-147 °C; IR (KBr) 1698, 1677, 1628 cm-1; 1H NMR (CDCl3,
300 MHz) δ 8.07-7.99 (m, 2H), 7.60 (t, J ) 7.5 Hz, 1H), 7.56-
7.47 (m, 5H), 7.45-7.37 (m, 2H), 7.31 (t, J ) 7.5 Hz, 1H), 7.00
(t, J ) 7.7 Hz, 1H), 5.55 (d, J ) 7.9 Hz, 1H), 3.96 (s, 3H), 3.09
(q, J ) 7.0 Hz, 4H), 1.35 (t, J ) 7.0 Hz, 6H); 13C NMR (CDCl3,
75 MHz) δ 190.2, 187.2, 176.3, 170.4, 162.4, 162.2, 145.2, 137.2,
135.8, 133.6, 133.4, 131.8, 131.5, 131.3, 131.0, 130.2, 129.3, 126.8,
126.0, 125.8, 124.3, 121.6, 101.3, 49.2, 42.3, 11.6; ESI-HRMS m/z
calcd for C31H28N2O6 + H (MH+) 525.20201, found 525.20164.
Reaction of Oxetanone 6 with 1 and 2 equiv of Diethylamine.
The reactions were conducted under the same conditions described
previously for nonaromatic primary amines and compounds 24 and
25 were isolated, respectively.
186-188 °C; IR (KBr) 1727, 1682, 1663, 1639 cm-1; H NMR
(CDCl3 + DMSO-d6, 300 MHz) δ 8.11-8.01 (m, 2H), 7.82-7.68
(m, 3H), 7.67-7.58 (m, 3H), 4.12-3.97 (m, 4H), 1.48 [t (broad),
J ≈ 6.8 Hz, 6H]; 13C NMR (CDCl3 + DMSO-d6, 75 MHz) δ 186.7,
180.0, 167.1, 161.3, 159.9, 148.5, 135.1, 133.1, 132.0, 131.2, 130.8,
129.8, 129.6, 125.8, 124.9, 124.4, 123.6, 120.7, 48.2, 12.0; ESI
positive 440 (M + Na)+, 418 (M + H)+. Anal. Calcd for C24H19-
NO6: C, 69.06; H, 4.59; N, 3.36. Found: C, 68.77; H, 4.59; N,
3.05.
2-{(Diethylamino)[3-(diethylamino)-1-oxo-1H-inden-2-yl]hy-
droxymethoxy}-3-hydroxynaphthoquinone (25): Yield 95%; mp
107-108 °C; IR (KBr) 1670, 1629 cm-1; H NMR (CDCl3, 300
1
MHz) δ 8.04 (d, J ) 7.5 Hz, 1H), 7.99 (d, J ) 7.5 Hz, 1H), 7.64-
7.56 (m, 3H), 7.54-7.46 (m, 3H), 4.07 (q, J ) 6.9 Hz, 4H), 3.06
(q, J ) 7.2 Hz, 4H), 1.47 (t, J ) 6.9 Hz, 6H), 1.31 (t, J ) 7.2 Hz,
6H); 13C NMR (CDCl3, 75 MHz) δ 188.9, 187.1, 176.3, 171.1,
162.8, 162.2, 137.1, 136.3, 133.7, 133.4, 132.1, 131.9, 131.5, 130.9,
125.9, 125.7, 124.1, 122.0, 99.5, 53.4, 42.1, 13.5, 11.5; ESI-HRMS
m/z calcd for C28H30N2O6 + H (MH+) 491.21766, found 491.21755.
Thermal Decomposition of Compound 25. Prolonged heating
(20 h) of a suspension of 25 in dimethoxyethane afforded after
column chromatography (silica gel, ethyl acetate) 3-(diethylamino)-
1H-inden-1-one (28). Yield 54%; oil; IR (KBr) 1690, 1650 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 7.47 (d, J ) 6.4 Hz, 1H), 7.33-
7.29 (m, 3H), 4.89 (s, 1H), 3.62 (broad, 4H), 1.37 (t, J ) 7.0 Hz,
6H); 13C NMR (CDCl3, 75 MHz) δ 191.6, 166.9, 137.3, 130.5,
130.1, 121.6, 120.7, 94.4, 47.2 (br), 13.5 (br); EI-MS m/z (%) 201
(M+, 69), 172 (51), 158 (100). Anal. Calcd for C13H15NO: C, 77.58;
H, 7.51; N, 6.96. Found: C, 77.32; H, 7.39; N, 7.07.
X-ray Crystal Structure Determination. Single crystals suitable
for X-ray structure determinations were obtained by adding diethyl
ether to a solution of 8b or 12a in methylene chloride. All C, N,
and O atoms were refined with anisotropic thermal parameters.
Hydrogen atoms were located and their positions refined for the
amine and hydroxy hydrogen atoms; all other hydrogen positions
were calculated for idealized positions.
Supporting Information Available: Spectral and analytical data
for compounds 8a-i, 10a-i, 12a-d, 14a-c, 16a-c, and 17a-c
and X-ray crystallographic files (CIF) for 8b and 12a. This material
is available free of charge via the Internet at http://pubs.acs.org.
3-Hydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl 3-(diethyl-
amino)-1-oxo-1H-indene-2-carboxylate (24): Yield 57%; mp
JO061879P
508 J. Org. Chem., Vol. 72, No. 2, 2007