An unexpected rearrangement that disassembles alkyne moiety through formal nitrogen atom insertion between two acetylenic carbons and related cascade transformations: New approach to Sampangine derivatives and polycyclic aromatic amides

Article abstract of DOI:10.1021/jo9008904

(Chemical Equation Presented) This work analyzes multiple new reaction pathways which originate from intramolecular reactions of activated alkynes with the appropriately positioned multifunctional hemiaminal moiety. Combination of experimental substituent

Full text of DOI:10.1021/jo9008904

pubs.acs.org/joc
An Unexpected Rearrangement That Disassembles Alkyne Moiety
Through Formal Nitrogen Atom Insertion between Two Acetylenic
Carbons and Related Cascade Transformations: New Approach to
Sampangine Derivatives and Polycyclic Aromatic Amides
Sergei F. Vasilevsky,*,† Denis S. Baranov,† Victor I. Mamatyuk,‡ Yury V. Gatilov,‡ and
Igor V. Alabugin*,§
†Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Science,
630090 Novosibirsk, Russian Federation, ‡N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russian Federation, and
§Department of Chemistry and Biochemistry, Florida State University,Tallahassee, Florida 32306
vasilev@ns.kinetics.nsc.ru; alabugin@chem.fsu.edu
Received May 12, 2009
This work analyzes multiple new reaction pathways which originate from intramolecular reactions of
activated alkynes with the appropriately positioned multifunctional hemiaminal moiety. Combination
of experimental substituent effects with Natural Bond Orbital (NBO) analysis revealed that alkyne
polarization controls partitioning between these cascades. A particularly remarkable transformation
leads to the formation of six new bonds at the two alkyne carbons due to complete disassembly of the
alkyne moiety and formal insertion of a nitrogen atom between the two acetylenic carbons of the
reactant. This reaction offers a new synthetic approach for the preparation of polycyclic aromatic
amides with a number of possible applications in molecular electronics. Another of the newly discovered
cascades opens access to substituted analogues of Sampangine alkaloids which are known for their
antifungal and antimycobacterial activity against AIDS-related opportunistic infection pathogens.
Introduction
development of well-choreographed cascade transformations2
which are impossible for their alkene “cousins” and in which
the alkyne moiety behaves as two functional groups “in one
Athough alkynes are well-recognized as convenient building
blocks for many useful transformations for organic synthesis,
medicinal chemistry, and materials science,1 their synthetic
potential is far from being fully exploited. In particular, due to
the possibility of facile formation of four new bonds at the
expense of the two π-bonds, alkynes lend themselves to the
(2) (a) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon
Bonds; Pergamon: Oxford, UK, 1986. (b) Curran, D. P. Synthesis 1988, 417–489.
(c) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237.
(d) Hildebrandt, D.; Dyker, G. J. Org. Chem. 2006, 71, 6728. (e) Iqbal, J.; Bhatia,
B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519. (f) Snider, B. B. Chem. Rev. 1996, 96,
339. (g) Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical Reactions;
VCH: Weinheim, Germany, 1996. (h) Gansauer, A.; Bluhm, H. Chem. Rev. 2000,100,
2771. (i) Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-VCH:
Weinheim, Germany, 2001. (j) Sibi, M. P.; Manyem, S.; Zimmerman, J. Chem. Rev.
2003, 103, 3263. (k) M€ullen, K.; Wegner, G. Electronic Materials: The Oligomer
Approach; Wiley-VCH: Weinheim, Germany, 1998.
*To whom correspondence should be addressed.
(1) Acetylene Chemistry: Chemistry, Biology and Material Science;
Diederich, F., Stang, P. J., Tykwinski, R. R., Eds.; Wiley-VCH: Weinheim,
Germany, 2005.
DOI: 10.1021/jo9008904
r
Published on Web 07/08/2009
J. Org. Chem. 2009, 74, 6143–6150 6143
2009 American Chemical Society

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SCHEME 1. Topological Analysis of the New Rearrangement/Fragmentation Reported in the Present Work (Top) and Selected Transfor-
mations of Alkynes Which Result in the Formation of Four New C-C/C-H Bonds (Bottom)
package”. A number of recently reported cascade transforma-
tions shown in Scheme 1 illustrate this notion by showing how
up to four new C-C and C-H bonds can be readily formed
from a suitably positioned alkyne moiety.3 In this work, we
wish to report an even more remarkable transformation that
leads to the formation of six new bonds at the two alkyne
carbons. This increase in the extent of structural changes is
possible due to complete disassembly of the alkyne moiety and
formal insertion of a nitrogen atom between the two acetylenic
carbons of the reactant.
One of the most important questions in any addition to an
FIGURE 1. Factors responsible for the multichannel character of
unsaturated system is that of regioselectivity. This question
translates into the problem of endo/endoselectivity if the
ring-closure reactions in adducts of peri-substituted acetylenyl-
9,10-anthraquinones and guanidine.
addition proceeds through a cyclic transition state.4 Due to
our long-standing interest in cyclizations of alkynes and
interaction of the alkyne moiety with spatially close func-
shown in Figure 1. This system combines an activated alkyne
tional groups,5 we sought a deeper understanding of factors
moiety with a polyfunctional hemiaminal group derived
from addition of guanidine to the carbonyl moiety of peri-
controlling such selectivity in cyclizations of alkynes through
analysis of possible cyclization pathways in the system
substituted acetylenic anthraquinones 1a-c. The presence of
several nucleophilic and electrophilic centers in this group
accounts for the multichannel mode of its interaction
with the adjacent alkyne and several reaction cascades
potentially originating from alternative cyclization modes.
We will also show below that change in the nature of
substituent R has the ability to control partitioning between
these cascades through modulation of the polarization of the
triple bond.
(3) (a) Zeidan, T.; Clark, R. J.; Kovalenko, S. V.; Ghiviriga, I.; Alabugin,
I. V. Chem.;Eur. J. 2005, 11, 4953. (b) Zeidan, T. A.; Kovalenko, S. V.;
Manoharan, M.; Clark, R. J.; Ghiviriga, I.; Alabugin, I. V. J. Am. Chem. Soc.
2005, 127, 4270. (c) C1-C5 cyclization of enediynes. Experiment: Alabugin,
I. V.; Kovalenko, S. V. J. Am. Chem. Soc. 2002, 124, 9052.Theory: Alabugin
I. V.; Manoharan, M. J. Am. Chem. Soc. 2003, 125, 4495. Applications:
Breiner, B.; Schlatterer, J. C.; Kovalenko, S. V.; Greenbaum, N. L.; Alabugin
I. V. Proc. Natl. Acad. Sci. 2007, 104, 13016-13021. Breiner, B.; Schlatterer,
J. C.; Kovalenko, S. V.; Greenbaum, N. L.; Alabugin, I. V. Angew. Chem.,
Int. Ed. 2006, 45, 3666. Kovalenko, S. V.; Alabugin, I. V. Chem. Commun.
2005, 1444. (d) Alabugin, I. V.; Gilmore, K.; Patil, S.; Manoharan, M.;
Kovalenko, S. V.; Clark, R. J.; Ghiviriga, I. J. Am. Chem. Soc. 2008, 30,
11535.
Whereas cyclizations of ortho-substituted aryl and hetaryl
acetylenes are a well-recognized and efficient approach to-
ward the preparation of annelated heterocyclic systems,6
(4) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
(5) Pickard, F. C. IV; Shepherd, R. L.; Gillis, A. E.; Dunn, M. E.;
Feldgus, S.; Kirschner, K. N.; Shields, G C.; Manoharan, M.; Alabugin, I.
V. J. Phys. Chem. A 2006, 110, 2517. Zeidan, T.; Kovalenko, S. V.;
Manoharan, M.; Alabugin, I. V. J. Org. Chem. 2006, 71, 962. Zeidan, T.;
Manoharan, M.; Alabugin, I. V. J. Org. Chem. 2006, 71, 954. Alabugin, I. V.;
Manoharan, M.; Kovalenko, S. V. Org. Lett. 2002, 4, 1119.
(6) Vasilevsky, S. F.; Tretyakov, E. V.; Elguero, J. Synthesis and Properties
of Acetylenic Derivatives of Pyrazoles. Adv. Heterocycl. Chem. 2002, 82, 1–99.
Tretyakov, E. V.; Knight, D. W.; Vasilevsky, S. F. J. Chem. Soc., Perkin Trans.
1999, 1, 3721. Sakamoto, T.; Kondo, Y.; Yamanaka, H. Heterocycles 1988, 87,
2225. Sandro, C.; Giancarlo, F.; Paola, P. J. Org. Chem. 1998, 63, 1001.
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SCHEME 2. Synthesis of Starting Materials
SCHEME 3. Reaction of Acetylenic Quinone 1a with Guanidine
SCHEME 4. Diverging Mechanistic Pathways Accounting for the Three Observed Products
data on cyclization of peri-substituted acetylenyl-9,10-an-
thraquinones are limited to our earlier report of a new
approach toward the synthesis of annelated heterocyclic
systems based on the reaction of peri-substituted acetyle-
nyl-9,10-anthraquinones and hydrazine.7b A search for new
cyclization types is important not only for the understanding
of the general connection between structure and reactivity of
organic compounds but also for expanding synthetic access
to the condensed systems.
Results and Discussion
The starting materials, 1-ethynylaryl-9,10-anthraquinones
1a-c, were prepared in 90-98% yields through Sonogashira
cross-coupling8 of 1-iodo-9,10-anthraquinone 2 with phenyla-
cetylene 3a, p-methoxyacetylene 3b, and p-nitrophenylacety-
lene 3c, using the catalytic Pd(PPh3)2Cl2-CuI-PPh3-Et3N
system (Scheme 2).
Interaction of guanidine with 1-phenylethynyl-9,10-an-
thraquinone 1a in refluxing n-butanol proceeded with the
(7) (a) Shvartsberg, M. S.; Ivanchikova, I. D.; Vasilevsky, S. F. Tetra-
hedron Lett. 1994, 35, 2077. (b) Shvartsberg, M. S.; Ivanchikova, I. D.;
Vasilevsky, S. F. Russ. Chem. Bull., Engl. Ed. 1998, 10, 1871. (c) Vasilevsky,
S. F.; Gornostaev, L. M.; Stepanov, A. A.; Arnold, E. V.; Alabugin, I. V.
Tetrahedron Lett. 2007, 48, 1867.
(8) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. A. Tetrahedron Lett.
1975, 50, 4457. (b) Brandsma, L.; Vasilevsky, S. F.; Verkruijsse, H. D. Applica-
tion of Transition Metal Catalysts in Organic Synthesis; Springer-Verlag:
NewYork, 1998; p 335.
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SCHEME 5. Suggested Mechanism for the Formation of Product 4a and Its Comparison with the Possible Mechanism for the Formation of
6-endo and 7-endo Products in the Earlier Reported Reaction of 1a with Hydrazine7b
SCHEME 6. Suggested Mechanism for the Formation of Product 5a
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SCHEME 7. Suggested Mechanism for the Formation of Products 6a-c
formation of three products 4a-6a separated on silica gel
(Scheme 3). Structures of the products were confirmed
through a combination of 2D NMR techniques.
(HMBC) 13C-1H couplings described in the SI. Because
the sequence of cascade transformations leading to the
formation of product 6a was unexpected and interes-
ting, we also investigated it through single-crystal X-ray
analysis, which unambiguously confirmed the proposed
1-phenyl-7H-dibenzo[de,h]isoquinolin-3,7-dione structure
(see the SI).9
We suggest that formation of these products stems from
three mechanistic pathways which diverge from a common
intermediate (Scheme 4). Both the polarized triple bond
of anthraquinone and the carbonyl groups present good
targets for nucleophiles. Formation of the hemiacetal in the
reaction of guanidine and the carbonyl moiety is likely to be
fast but reversible and, thus, should result in a productive
reaction pathway only when a subsequent exothermic step is
available.
In particular, assignment of signals in 1H and 13C NMR
spectra for compound 6a in DMSO-d6 has been accom-
1
plished via 2D NMR spectroscopy including H-1H cor-
relation with double quantum filter (COSYDQF), inverse
13C-1H correlations of direct (HSQC) and long-range
(9) Cambridge Structural Database (Cambridge, UK, version 5.29) has
no information about the structure of compounds containing the 3H-
dibenzo[de,h]isoquinolin-3,7(2H)dione moiety. The tetracyclic skeleton of
compound 5 is folded along the C7-C11B line by 7.8°. Otherwise, the
˚
molecule is flat within (0.181 A. The Ph group is rotated relative to the core
by 70.4°. The centrosymmetric dimers in the crystal are organized through
˚
N2-H O1 H-bonds (N-H 0.92(3), H O 1.92(3) A, N-H O 175
3 3 3
3 3 3
3 3 3
(2)°). Molecules in the crystal are organized in the herringbone packing with
significant π-stacking interactions (the intermolecular distances of 3.54 A).
˚
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TABLE 1. Optimized Geometries and Relative Energies of Selected Intermediates for the Formation of Product 6a at the B3LYP/6-31G(d,p) Level
SCHEME 8. Substituent Effect at the Competition between Two Cyclization Cascades
We believe that product 4a is formed from the regioselec-
tive attack of hemiaminal nitrogen at the β-carbon of the
alkyne.10 The 6-endo-dig selectivity for this closure is con-
sistent with the triple bond polarization by the quinone
moiety (vide infra). On the other hand, even though
5-exo-dig closures are often favored stereoelectronically
relative to their 6-endo-dig counterparts,11 the 5-exo attack
of the oxygen nucleophile in this system proceeds against the
triple bond polarization. An interesting possibility that
underscores the polyfunctional character of the guanidine
moiety is that presence of an appropriately positioned N-H
bond near the developing negative center in the 5-exo-
dig transition state (Scheme 4, top right) may provide an
additional factor in favor of such a pathway. This hypothesis
is consistent with the absence of 5-exo-attack of the nitrogen
atom, where such assistance is impossible, and with the
observation that the reaction of quinone 1a with a nitrogen
nucleophile is incapable of such assistance (hydrazine) does
not provide any products derived from this path.7 This
observation also suggests that the competition between the
N-6-endo and O-5-exo-products 4a and 6a may be fine-tuned
through the change in the triple bond polarization (vide
infra). Finally, the minor product is consistent with an
external nucleophilic attack at the electron-deficient end of
the polarized triple bond with concomitant trapping of the
developing carbon nucleophile with the CdN moiety of
guanidine in a 6-endo-dig manner.
Formation of phenyl-7H-dibenzo[de,h]quinolin-7-one 4a
can be rationalized through consecutive addition of a gua-
nidinium amino group at the carbonyl carbons and the triple
bond (in a 6-endo fashion) with the subsequent elimination
of water and NH2CN (or hydroxylamine and HCN).
(10) At this point, we cannot exclude an alternative mechanism that
includes initial attack of guanidine at the triple bond followed by cyclization
of the intermediate on the carbonyl. Note, however, that the positive charge
is significantly larger at the carbonyl carbon than it is at either of the two
carbons of the alkyne moiety (Table 2).
(11) Alabugin, I. V.; Manoharan, M. J. Am. Chem. Soc. 2005, 127, 12583.
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TABLE 2. Natural Bond Orbital (NBO)14 Analysis of Substituent Effects on Polarization of the Triple Bond and the Adjacent Carbonyl Group in
Anthraquinones 1a-c at the B3LYP/6-31G(d,p) Level15
p-OMe-Ph, 1b
1.965
49.19
1.839
52.53
1.955
66.27
0.538/-0.004/0.044
Ph, 1a
p-NO2Ph, 1c
1.966
49.13
1.834
50.65
1.955
66.29
0.542/0.035/0.023
πin, population
π*in, polarization (% at β-carbon)
1.966
49.38
1.840
51.99
1.955
66.24
π
out, population
π*out, polarization (% at β-carbon)
CO, population
π
π*CO, polarization (% at carbon)
charges C(O)/CR/Cβ
0.540/0.004/0.042
SCHEME 9. Summary of Synthetic Opportunities Offered by the New Cascade Transformations
The 6-endo-closure is similar to that observed earlier in the
reaction of 1a with hydrazine7b (Scheme 5).
and the fragmentation/recyclization sequences B and C lie
respectively ca. 20 and 27 kcal/mol lower in energy than the
first hemiaminal intermediate A.
Formation of 2-amino-3-benzoyl-7H-dibenzo[de,h]quino-
lin-7-one 5a can be described through several mechanisms,
the shortest of which is given in Scheme 6. The key step in the
proposed sequence is nucleophilic attack at the remote
acetylenic carbon with concomitant trapping of the devel-
oping vinyl anion by the internal CdNH electrophile in the
6-exo fashion. The incoming nucleophile may be guanidine,
butanol (the solvent), or water produced in the previous step
of the reaction cascade. Transformation of the cyclized
intermediate in the final product is accompanied by aroma-
tization, which should provide the driving force for the C-N
bond cleavage that furnishes compound 5a.
However, formation of the rearranged product 6a was
rather unusual and should result from a cascade transfor-
mation that follows addition, cyclization, rearrangement,
and elimination of guanidine fragments. The exact me-
chanism for the formation of isoquinoline-3,7-dione 6a is
yet unknown. A possible sequence of steps outlined in
Scheme 7 involves the 5-exo-dig closure followed by a
fragmentation-recyclization sequence that resembles
the retro-aldolization-aldol condensation sequence of
the Fujimoto-Belleau reaction12 and the Petasis-Ferrier
rearrangement.13
To test the importance of triple bond polarization in
this mechanism, we expanded the list of substrates and
investigated the reactivity of p-nitro- and p-methoxy-
substituted acetylenes 1b and 1c. The presence of an
acceptor nitro group at the terminal aromatic ring in-
creases the yield for the unusual products 6 by almost
50%. This observation further supports the notion that
this mechanistic path starts with 5-exo-dig nucleophilic
attack at the R-carbon. Interestingly, interaction of ni-
troacetylene 1c also led to the formation of a small
amount (∼14%) of 1-(p-aminophenylethynyl)-9,10-an-
thraquinone 7, the product of the nitro-group reduction.
On the contrary, the presence of a donor methoxy group
had the opposite effect, favoring external nucleophilic
attack at the terminal carbon and the formation of com-
pound 5b at the expense of compounds 4 and, to some
extent, 6 (Scheme 8).
These results are consistent with the analysis of acety-
lenic π-bonds polarization by the Natural Bond Orbital
(NBO) analysis. These results summarized in Table 214,15
show that the presence of the donor substituent increases
the out-of-plane π-density at the R-carbon of the triple
bond, whereas the electron acceptor nitro group has the
opposite effect. In contrast, both the in-plane π-bond and
the adjacent carbonyl moiety show very little perturbation
by the substituents.
We tested the feasibility of several intermediates involved
in this mechanism by calculating their relative energies at
the B3LYP/6-31G(d,p) level. Results summarized in Table 1
suggest that indeed the products of 5-exo cyclization
(12) Zwahlen, K. D.; Horton, W. J.; Fujimoto, G. I. J. Am. Chem. Soc.
1957, 79, 3131. Recent examples: Sollogoub, M.; Mallet, J.-M.; Sinay, P.
(14) NBO 4.0: Glendening, E. D.; Badenhoop, J. K.; Reed, A. E.;
Carpenter, J. E.; Weinhold, F. Theoretical Chemistry Institute, University
of Wisconsin, Madison, WI, 1996. Applications to electronic structure of
acetylenes: Alabugin, I. V.; Manoharan, M. J. Am. Chem. Soc. 2005, 127,
12583. Alabugin, I. V.; Manoharan, M. J. Am. Chem. Soc. 2005, 127, 9534.
(15) (a) Becke, A. D. Phys. Rev. A 1988, 38, 3098. (b) Lee, C. T.; Yang, W.
T.; Parr, R. G. Phys. Rev. B 1988, 37, 785. (c) Stephens, P. J.; Devlin, F. J.;
Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98, 11623. All
computations were performed with the Gaussian 03 program: Frisch, M. J.
et al. Gaussian 03, revision C.01; Gaussian, Inc., Wallingford, CT, 2004 (see
the SI for the complete reference ).
ꢀ
Angew. Chem., Int. Ed. 2000, 39, 362; Sollogoub, M.; Pearce, A. J.; Herault,
A.; Sinay, P. Tetrahedron: Asymmetry 2000, 11, 283.Summary: Meek, S. J.;
Harrity, J. P. A. Tetrahedron 2007, 63, 3081.
(13) Ferrier, R. J.; Middleton, S. Chem. Rev. 1993, 93, 2779. Petasis,
N. A.; Lu, S.-P. Tetrahedron Lett. 1996, 37, 141. Petasis, N. A.; Lu, S.-P.
J. Am. Chem. Soc. 1995, 117, 6394.For selected examples, see also: Zhang, Y.;
Reynolds, N. T.; Manju, K.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 9720.
Shenoy, S. R.; Woerpel, K. A. Org. Lett. 2005, 7, 1157. Smith, A. B. III;
Bosanac, T.; Basu, K. J. Am. Chem. Soc. 2009, 131, 2348.
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Conclusion
lit. mp 207-208 °C. All spectral data are analogous to literature
data.21
In summary, we have illustrated the possibility of
multiple reaction pathways originating from the reaction
of a polarized triple bond with the appropriately posi-
tioned multifunctional hemiaminal moiety. The most
remarkable of these reactions leads to the formal clea-
vage of the triple bond and insertion of one of the
guanidine nitrogen atoms between the two acetylenic
carbons. Although further work is needed to fully under-
stand the mechanistic subtleties involved in this process,
it is clear that, besides its uniqueness from the conceptual
point of view, this chemistry also offers a new synthetic
approach for the preparation of polycyclic aromatic
amides.
In particular, one of these cascades opens access to
substituted analogues of Sampangine alkaloids which are
known for their antifungal and antimycobacterial activity
against AIDS-related opportunistic infection patho-
gens16 whereas the other cascade, which leads to the
formal transposition of N and C atoms, leads to molecules
which may be useful as a structural element for hydro-
phobic dimerizations17 as well as for the construction of
systems for fundamental studies of electron and energy
transfer phenomena,18 design of photovoltaic devices,
organic field effect transistors, and light emitting diodes
(Scheme 9).19,20
The yield of 1-phenyl-7H-dibenzo[de,h]isoquinolin-3,7-dione
6a is 200 mg (31%), mp >360 °C (from 1,4-dioxane). IR (cm-1
)
ν 1648, 1670 (CdO), 3055 (NH); 1H NMR ((CD3)2SO,
300 MHz) δ 12.08 (s, 1H, NH), 8.70-8.65 (m, 2H, H-4, H-6),
8.25 (dd, J = 1.2, 7.8 Hz, 1H, H-8), 7.86 (t, J = 7.7 Hz, 1H, H-5),
7.65-7.55 (m, 5H, Ph), 7.35 (t, J = 7.8 Hz, 1H, H-9), 7.23-7.17
(m, 1H, H-10), 6.81 (d, J = 8.3 Hz, 1H, H-11); 13C NMR
((CD3)2SO, 100 MHz) δ 181.7 (C-7), 160.9 (C-3), 145.8 (C-1),
135.1 (C-11a), 134.6 (C-11c), 135.5 (Ci), 132.9 (C-6), 132.6 (C-4),
131.8 (C-10), 130.3 (Cp), 129.9 (C-7a), 129.5 (Co), 129.3 (Cm),
127.5 (C-6a), 127.1 (C-8), 127.0 (C-5), 127.0 (C-9), 126.4 (C-11),
124.7 (C-3a), 104.1 (C-11b); HRMS calcd for C22H13NO2
323.0946, found 323.0946.
Experimental Section
General Procedure for Reaction of 1-Acetylenyl-9,10-anthra-
quinones with Guanidine. A mixture of guanidine (19.5 mmol,
19.5 mL of 1 M solution in methanol) and the respective
anthraquinone 1a-c (3.25 mmol) was refluxed in 50 mL
of butanol-1 for 18-20 h. Under these conditions, the
amount of unreacted 1-acetylenylanthraquinones is about
20-35%. Longer heating leads to partial thermal decom-
position and complicates isolation and purification of reac-
tion products. Solvent was evaporated in vacuo. The mix-
ture was purified by column chromatography on silica gel
(d = 25 mm, h = 170 mm, elution with benzene followed
by ethyl acetate). Subsequent recrystallization gave pure
compounds 4-7.
The yield of 2-amino-3-benzoyl-7H-dibenzo[de,h]quinolin-7-
one 5a is 130 mg (19%), mp 201-201.3 °C (from benzene). IR
(cm-1) ν 1634, 1667 (CdO), 3368, 3492 (NH2); 1H NMR
(CDCl3, 400 MHz) δ 8.81 (dd, J = 1.2, 7.8 Hz, 1H, H-11),
8.37 (dd, J = 1.2, 7.8 Hz, 1H, H-8), 8.24 (dd, J = 1.2, 7.0 Hz, 1H,
H-6), 7.77 (td, J = 1.36, 7.8 Hz, 1H, H-10), 7.72-7.69 (m, 2H,
Ho), 7.66 (td, J = 1.36, 7.8 Hz, 1H, H-9), 7.59-7.54 (m, 1H, Hp),
7.52 (dd, J = 1.2, 8.6 Hz, 1H, H-4), 7.47-7.39 (m, 3H, H-5, Hm),
5.95 (s, 2H, NH2); 13C NMR (CDCl3, 100 MHz) δ 197.1 (C-12),
183.3 (C-7), 155.1 (C-2), 151.1 (C-11b), 139.8 (Ci), 136.5 (C-6a),
135.5 (C-11a), 133.7 (C-10), 133.1 (Cp), 132.5 (C-7a), 131.0 (C-
9), 130.7 (C-4), 130.4 (C-5), 129.4 (Co), 129.0 (C-3a), 128.7 (Cm),
127.4 (C-8), 125.6 (C-6), 125.4 (C-11), 117.7 (C-11c), 106.1
(C-3); HRMS calcd for C23H14N2O2 350.1055, found 350.1055.
For 1a, the yield of phenyl-7H-dibenzo[de,h]quinolin-7
-one 4a is 70 mg (10%), mp 207.5-208.5 °C (from benzene),
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Acknowledgment. This work was supported by Inter-
disciplinary grant No. 93 of SB of the Russian Academy of
Sciences (2009-2011), and the Chemical Service Centre of SB
RAS. Work at FSU was supported by the National Science
Foundation (CHE-0316598).
€
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Note Added after ASAP Publication. Some endo were changed
to exo on pages 6 and 7 in the version published July 14, 2009.
Supporting Information Available: Yields and experimental
conditions for the cyclizations, synthesis of starting materials,
1H and 13C NMR spectra, details of X-ray crystallographic
analysis, energies, and geometries for reactants and intermedi-
ates calculated at the B3LYP/6-31G(dp) level. This material is
available free of charge via the Internet at http://pubs.acs.org.
€
Zhang, J.; Grimsdale, A. C.; Mullen, K.; Mackenzie, J. D.; Silva, C.; Friend,
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