Synthesis of quinolines from 3-formylchromone

Article abstract of DOI:10.1021/jo800950y

(Chemical Equation Presented) A facile and versatile procedure for the synthesis of 3-(2-hydroxybenzoyl)quinolines and 7H-chromeno[3,2-c]quinolin-7- ones was elaborated on the basis of TMSCl-mediated recyclization of 3-formylchromone with various anilines. Limitations and scope of this methodology were established, and a possible mechanism for the heterocyclizations was proposed.

Full text of DOI:10.1021/jo800950y

efficient approaches to the quinolines. It occurs through
condensation of 1,3-dicarbonyl compounds with primary anilines
followed by acid-catalyzed ring closure of the intermediate
Schiff bases.8–11 3-Fomylchromone 1 is a latent 1,3-dialdehyde
bearing a masked 2-hydroxybenzoyl fragment at the meso-posi-
tion.12,13 Recently we have shown that the recyclization and [3
+ 3] cyclocondensation of 3-formylchromones with CH-active
compounds such as cyanoacetamides,14a amino heterocycles,5a
and benzimidazoles14b readily gives functionally diverse sub-
Synthesis of Quinolines from 3-Formylchromone
Andrey S. Plaskon,†,‡ Sergey V. Ryabukhin,*,†,‡
Dmitriy M. Volochnyuk,†,§ Konstantin S. Gavrilenko,†,‡
Alexander N. Shivanyuk,†,‡ and Andrey A. Tolmachev‡
Enamine Ltd., 23 A. MatrosoVa st., KyiV 01103, Ukraine,
National Taras SheVchenko UniVersity, 62 Volodymyrska st.,
KyiV 01033, Ukraine, and Institute of Organic Chemistry,
National Academy of Sciences of Ukraine,
5 Murmanska st., KyiV 02094, Ukraine
(3) (a) Kouznetsov, V. V.; Vargaz Mendez, L. Y.; Melendez Gomez, C. M.
Curr. Org. Chem. 2005, 9, 141–161. (b) Ishkawa, T.; Manabe, S.; Aikawa, T.;
Kudo, T.; Saito, S. Org. Lett. 2004, 6, 2361–2364. (c) Sangu, K.; Fuchibe, K.;
Akiyama, T. Org. Lett. 2004, 6, 353–355. (d) Kobayashi, K.; Yoneda, K.;
Miyamoto, K.; Morikawa, O.; Konishi, H. Tetrahedron 2004, 60, 11639–11645.
(e) Wang, J.; Fan, X.; Zhang, X.; Han, L. Can. J. Chem. 2004, 82, 1192–1196.
(f) Palimkar, S. S.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V.
J. Org. Chem. 2003, 68, 9371–9378. (g) Du, W.; Curran, D. P. Org. Lett. 2003,
5, 1765–1768. (h) Jiang, B.; Yui-Gui, S. J. Org. Chem. 2002, 67, 9449–9451.
(i) Amii, H.; Kishikawa, Y.; Uneyama, K. Org. Lett. 2001, 3, 1109–1112.
(4) (a) Deady, L. W.; Desneves, J.; Kaye, A. J.; Finlay, G. J.; Baguley, B. C.;
Denny, W. A. Bioorg. Med. Chem. 2001, 9, 445–452. (b) Chen, J.; Deady, L. W.;
Desneves, J.; Kaye, A. J.; Finlay, G. J.; Baguley, B. C.; Denny, W. A. Bioorg.
Med. Chem. 2000, 8, 2461–2466. (c) Deady, L. W.; Desneves, J.; Kaye, A. J.;
Finlay, G. J.; Baguley, B. C.; Denny, W. A. Bioorg. Med. Chem. 2000, 8, 977–
984. (d) Deady, L. W.; Kaye, A. J.; Finlay, G. J.; Baguley, B. C.; Denny, W. A.
J. Med. Chem. 1997, 40, 2040–2046.
ryabukhin@mail.enamine.net
ReceiVed May 2, 2008
(5) For the synthesis of 3-(2-hydroxybenzoyl)quinoline, see:(a) Ryabukhin,
S. V.; Plaskon, A. S.; Volochnyuk, D. M.; Tolmachev, A. A. Synthesis 2007,
1861–1871. (b) Basavaiah, D.; Reddy, R. J.; Rao, J. S. Tetrahedron Lett. 2006,
47, 73–77.
A facile and versatile procedure for the synthesis of 3-(2-
hydroxybenzoyl)quinolines and 7H-chromeno[3,2-c]quinolin-
7-ones was elaborated on the basis of TMSCl-mediated
recyclization of 3-formylchromone with various anilines.
Limitations and scope of this methodology were established,
and a possible mechanism for the heterocyclizations was
proposed.
(6) For recent syntheses of 3-benzoylquinoline derivatives, see:(a) Yoon, K.;
Ha, S. M.; Kim, K. J. Org. Chem. 2005, 70, 5741–5744. (b) Patteux, C.;
Levacher, V.; Dupas, G. Org. Lett. 2003, 5, 3061–3063. (c) Mahata, P. K.;
Venkatesh, C.; Syam Kumar, U. K.; Ila, H.; Junjappa, H. J. Org. Chem. 2003,
68, 3966–3975. (d) Singh, G.; Singh, L.; Ishar, M. P. S. Tetrahedron 2002, 58,
7883–7890. (e) Singh, G.; Singh, R.; Girdhar, N. K.; Ishar, M. P. S. Tetrahedron
2002, 58, 2471–2480. (f) Harrowven, D. C.; Sutton, B. J.; Coulton, S.
Tetrahedron Lett. 2001, 42, 2907–2910. (g) Ishar, M. P. S.; Kumar, K.; Singh,
R. Tetrahedron Lett. 1998, 39, 6547–6550.
(7) (a) Normand-Bayle, M.; Benard, C.; Zouhiri, F.; Mouscadet, J.-F.; Leh,
H.; Thomas, C.-M.; Mbemba, G.; Desmaele, D.; d’Angelo, J. Bioorg. Med. Chem.
Lett. 2005, 15, 4019–4022. (b) Whitesitt, C. A.; Simon, R. L.; Reel, J. K.;
Sigmund, S. K.; Phillips, M. L.; Shadle, J. K.; Heinz, L. J.; Koppel, G. A.;
Hunden, D. C.; Lifer, S. L.; Berry, D.; Ray, J.; Little, S. P.; Liu, X.; Marshall,
W. S.; Panetta, J. A. Bioorg. Med. Chem. Lett. 1996, 6, 2157–2162. (c) Evans,
D.; Cracknell, M. E.; Saunders, J. C.; Smith, C. E.; Williamson, W. R. N.;
Dawson, W.; Sweatman, W. J. F. J. Med. Chem. 1987, 30, 1321–1327.
(8) (a) Combes, A. Bull. Soc. Chim. Fr. 1888, 49, 89. (b) Bergstrom, F. W.
Chem. ReV. 1944, 35, 77–277.
The functionalized quinolines are attractive compounds for
drug discovery since many of them have been shown to exhibit
excellent biological activities.1 Therefore, the development of
facile methodologies for the synthesis of highly functionalized
quinoline derivatives represents a challenge in medicinal
chemistry.2,3 For example oxoindeno[1,2-b]quinolines have
shown strong binding to DNA and efficient inhibition DNA
topoisomerase 1 that were associated with their well pronounced
anticancer activities.4 3-Benzoylquinolines5,6 are inhibitors of
HIV-1 replication7a and cathepsin D7b and possess antianaphy-
lactic activity.7c The Combes synthesis is one of the most
(9) For using 1,3-dialdehydes in Combes synthesis, see:(a) Gaillard, S.;
Papamicael, C.; Marsais, F.; Dupas, G.; Levacher, V. Synlett 2005, 441–444.
(b) Nair, J. S.; Rajasekharan, K. N. Indian J. Chem. Sect. B 2004, 43, 1944–
1949. (c) Takeuchi, I.; Ushida, M.; Hamada, Y.; Yuzuri, T.; Suezawa, H.; Hirota,
M. Heterocycles 1995, 41, 2221–2231. (d) Magnus, P. D.; Iliadis, T.; Eisenbeis,
S. A.; Fairhurst, R. A. U.S. Patent 5442065, 1995; Chem. Abstr. 123, 313637.
(e) Sequeria, S.; Seshadri, S. Indian J. Chem. Sect. B 1987, 26, 436–439.
(10) For using 1,3-ketoaldehydes in Combes synthesis, see:(a) Sharma, K. S.;
Singh, S. P.; Kumari, S. Indian J. Chem. Sect. B 1994, 33, 1191–1192. (b)
Acheson, R. M.; Birtwistle, D. H.; Constable, E. C.; Tester, G. G.; Whitehead,
J. W. F.; Wyatt, P. B. J. Chem. Res. Synop. 1986, 269. (c) Kessar, S. V.; Singh,
I.; Kumar, A. Tetrahedron Lett. 1965, 7, 2207–2209.
† Enamine Ltd.
‡ National Taras Shevchenko University.
§ National Academy of Sciences of Ukraine.
(1) (a) Balasubramanian, M.; Keay, J. G. In ComprehensiVe Heterocyclic
Chemistry II; Katritzky, A. R., ; Rees, C. W., ; Scriven, E. F. V., Eds.; Pergamon
Press: Oxford, 1996; Vol. 5, pp 245-300. (b) Catoen-Chackal, S.; Facompre,
M.; Houssin, R.; Pommery, N.; Goossens, J.-F.; Colson, P.; Bailly, C.; Henichart,
J.-P. J. Med. Chem. 2004, 47, 3665–3673. (c) Vazquez, M. T.; Romero, M.;
Pujol, M. D. Bioorg. Med. Chem. 2004, 12, 949–956. (d) Chen, Y.-L.; Chen,
I.-L.; Lu, C.-M.; Tzeng, C.-C.; Tsao, L.-T.; Wang, J.-P. Bioorg. Med. Chem.
2004, 12, 387–392. (e) Chen, Y. J.; Fang, K. C.; Sheu, J.-Y.; Hsu, S. L.; Tzeng,
C. C. J. Med. Chem. 2001, 44, 2374–2377.
(11) For using 1,3-diketones in Combes synthesis, see:(a) Hungarian Patent
Appl. HU 200401607, 2006; Chem. Abstr. 2007, 147, 385856. (b) Yamashkin,
S. A.; Oreshkina, E. A.; Romanova, I. S.; Yurovskaya, M. A. Chem. Heterocycl.
Compd. (Engl.Transl.) 2005, 41, 1280–1289. (c) Boltacheva, N. S.; Filyakova,
V. I.; Charushin, V. N. Russ. J. Org. Chem. 2005, 41, 1452–1457. (d) Singh,
B. K. N.; Fernandes, P. S. Indian J. Heterocycl. Chem. 2003, 13, 19–24. (e)
Volochnyuk, D. M.; Pushecnikov, A. O.; Krotko, D. G.; Sibgatulin, D. A.;
Kovaleva, S. A.; Tolmachev, A. A. Synthesis 2003, 1531–1540. (f) Karpenko,
N. S.; Filyakova, V. I.; Matochkina, E. G.; Kodess, M. I.; Pashkevich, K. I.
Russ. Chem. Bull. 2003, 52, 1215–1216. (g) Aly, A. A. Tetrahedron 2003, 59,
1739–1747. (h) Sanna, P.; Carta, A.; Paglietti, G. Heterocycles 1999, 51, 2171–
2181. (i) El ouar, M.; Knouzi, N.; El kihel, A.; Essassi, E. M.; Benchidmi, M.;
Hamelin, J.; Carrier, R.; Danion-Bougot, R. Synth. Commun. 1995, 25, 1601–
1604.
(2) (a) Gilchrist, T. L. Heterocyclic Chemistry, 3rd ed.; Adison-Wesley
Longman: Essex, 1997; pp 158-164. (b) Jones, G. In ComprehensiVe Hetero-
cyclic Chemistry; Katritzky, A. R.; Rees, A. R., Eds.; Pergamon: Oxford, 1984;
Vol. 2, p 395. (c) Jones, G. In ComprehensiVe Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon Press: Oxford,
1996; Vol. 5, pp 167-243.
6010 J. Org. Chem. 2008, 73, 6010–6013
10.1021/jo800950y CCC: $40.75 2008 American Chemical Society
Published on Web 07/02/2008

SCHEME 1
SCHEME 2
SCHEME 3
stituted pyridines. The present study was undertaken in order
to develop a facile method for the synthesis of 3-(2-hydroxy-
benzoyl)quinolines through the coupling of 3-formylchromone
1 with anilines.
Surprisingly, the reactions of anilines 4a-i with 3-formyl-
chromone (TMSCl, DMF) led to 7H-chromeno[3,2-c]quinolin-
7-ones15 5a-i (Scheme 2) in 39-63% yield. No quinolines of
type 3 were detected in the reaction mixtures by LCMS. The
fact that the substituents in molecules 4 withdraw electrons from
the ortho-positions to the amino group or increase the electron
density on the nitrogen atom indicate that anilines 4 react as
N-nucleophiles. The reaction of 3-chloroaniline with 3-formyl-
chromone gave a multicomponent mixture containing the
corresponding compounds 3 (33%) and 5 (14%) and three
unidentified products. 3,4-Dichloroaniline 4j whose C-nucleo-
philicity is decreased by the presence of a chlorine atom at the
meta-position to the amino group reacted with 1 to give
chromenoquinolin-7-one 5j in 51% yield.
On the basis of our previous studies,5a,14 we considered
TMSCl as a potential promoter and water scavenger for the
reaction of 3-formylchromone with anilines unsubstituted at the
ortho-position that might result in various o-hydroxybenzoyl
quinolines. The present research was undertaken in order to
determine limitation and establish the scope of this reaction with
various substituted anilines. The reaction of substituted anilines
2a-l with 3-formylchromone gave quinolines 3a-l in 35-87%
yield. (Scheme 1). It seems likely that the reactivity of the ortho-
position in substituted anilines is influenced by +M and sterical
effect of the functional groups in meta- and para-positions. This
indicates that on the first bimolecular step of the reaction anilines
2 react as C-nucleophiles. The reactions of the ortho-substituted
anilines with formylchromone resulted in multicomponent
mixtures, which according to LCMS contain less than 20% of
the corresponding quinolines 3.
TMSCl can activate 3-formylchromone 1 through addition
to aldehyde or ketone CdO bonds to give intermediates 6a and
6b, respectively16 (Scheme 3).
Apparently intermediate 6a is more electrophilic and more
reactive than resonance-stabilized O-trimethylsilyl-3-formyl-
chromone chloride 6b. Scheme 4 outlines possible mechanisms
for the formation of quinolines 3 and 6 starting from activated
3-formylchromone 6a. Amines 2 are likely to react with 6a as
C-nucleophiles to give intermediate 7, which after activation
of the keto group and double bond of chromone undergoes
intramolecular N-arylation to give intermediate 8. Elimination
of HMDS from 8 can result in N-silylated quinolyl chromone
9, which can be transformed into trimethylsiloxybenzoyl quino-
(12) Reviews:(a) Ghosh, C. K. J. Heterocycl. Chem. 1983, 20, 1437–1445.
(b) Sabitha, G. Aldrichimica Acta 1996, 29, 15–25. (c) Ghosh, C. K. Indian
J. Chem. Sect. B 1997, 36, 968–980. (d) Ghosh, C. K. Heterocycles 2004, 63,
2875–2898.
(13) Recent publications:(a) Chovancova´, J.; Stankovie`ova´, H.; Ga´plovsky´,
A.; La´cova´, M.; Puchala, A. J. Heterocycl. Chem. 2006, 43, 843–848. (b) Ghosh,
T.; Bandyopadhyay, C. J. Heterocycl. Chem. 2006, 43, 1431–1434. (c)
Iaroshenko, V. O.; Groth, U.; Kryvokhyzha, N. V.; Obeid, S.; Tolmachev, A. A.;
Wesch, T. Synlett 2008, 343–346. (d) Figueiredo, A. G. P. R.; Tome, A. C.;
Silva, A. M. S.; Cavaleiro, J. A. S. Tetrahedron 2007, 63, 910–917.
(14) (a) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; Tolmachev,
A. A. Synlett 2004, 2287–2290. (b) Ryabukhin, S. V.; Plaskon, A. S.;
Volochnyuk, D. M.; Tolmachev, A. A. Synthesis 2007, 3155–3162. (c)
Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; Pipko, S. E.; Tolmachev,
A. A. Heterocycles 2008, 75, 583–597. (d) Plaskon, A. S.; Ryabukhin, S. V.;
Volochnyuk, D. M.; Tolmachev, A. A. Synthesis 2008, 1069–1077. (e) Plaskon,
A. S.; Ryabukhin, S. V.; Volochnyuk, D. M.; Shivanyuk, A. N.; Tolmachev,
A. A. Tetrahedron 2008, 64, 5933–5943.
(15) Some compounds of type 5 have been previously prepared via
complicated multistep procedures: (a) Partridge, M. W.; Bloomfield, D. G.;
Vipond, H. J. J. Chem. Soc. C 1970, 2647–2653. (b) Khodair, A. I.; Abbasi,
M. M. A.; Ibrahim, El-Sayed I.; Soliman, A. H.; ElAshry, El-Sayed H.
Heterocycl. Commun. 1999, 5, 577–584.
(16) Iwasaki, H.; Kume, T.; Yamamoto, Y.; Akiba, K. Heterocycles 1988,
27, 1599–1602.
J. Org. Chem. Vol. 73, No. 15, 2008 6011

SCHEME 4
line 10 through intramolecular migration of the trimethylsilyl
group from the nitrogen to oxygen atom and breaking the C-O
bond.
d6) and is deshielded as a result of the formation of the stable
intramolecular bond to the adjacent carbonyl group. The typical
13C NMR spectrum of quinolines 3 contains the signal of a
carbonyl carbon atom at δ ≈ 193.1-196.6 ppm and a
characteristic set of signals for the carbons of ortho-acylated
phenol ring and for the carbons of the pyridine fragment. In
the typical IR spectra of quinolines 3, a wide absorption band
at 3650-3300 cm-1 corresponding to valence vibrations of the
hydroxyl group, and an intensive peak at 1622-1639 cm-1
corresponding to valence vibrations of carbonyl group is present.
The 1H NMR spectra of compounds 5 contains a set of signals
for the ortho-substituted aryl ring of the chromone residue and
a singlet for the methine proton of the quinoline fragment
(9.3-9.6 ppm in DMSO-d6 or 9.9-10.2 in CF3COOD), whereas
no signal was detected for the phenolic OH group. The 13C NMR
spectra of compounds 5 contains the signal of carbonyl carbon
atom at δ ≈ 175.5-175.8 ppm (DMSO-d6) or δ ≈ 175.8-185.5
ppm (CF3COOD), a set of signals for the ortho-substituted aryl
ring of the chromone residue, and a signal for the C-2 of the
quinolinefragment(145.5-148.7ppminDMSO-d6or145.2-148.1
in CF3COOD).
The reaction of N-nucleophilic amine 4 with intermediate 6a
seems likely to give intermediate 11, which after activation of
the keto group and the adjacent double bond of chromone
undergoes intramolecular cyclization through electrophilic
substitution at the ortho-position to the aniline nitrogen atom.
The intramolecular elimination of HMDS is likely to result in
the silylated dihydroquinoline 13 intermediate, which can be
transformed into compound 5 through the loss of hydride and
hydrolysis. It seems plausible that the long distance between
the silicon and oxygen atom at position 4 makes impossible
the intramolecular migration of the trimethylsilyl group resulting
in the opening of the pyrone ring. After quenching of the
reaction mixture, dihydroquinoline 14 seems likely to dispro-
portionate into final product 5 and tetrahydroquinoline 15.
Accordingly, the LCMS studies of the reaction mixtures revealed
the presence of tetrahydroquinolines 15 as a byproduct of
quinolines 5. Unfortunately the preparative HPLC failed to
isolate individual compounds 15.
The structure of compound 5k was unambiguously deter-
mined by single crystal X-ray analysis17 (see Figure 1, X-ray
crystal structure determination, in Supporting Information). In
the crystalline state plane molecules of 5k are involved in
stacking interactions to give infinite columns in the crystal.
In conclusion, we have elaborated efficient synthetic proce-
dures for the preparation of functionalized quinolines from
3-formylchromone and substituted anilines using TMSCl as a
promoter and water scavenger. The reaction of 3-formyl-
chromone with C-nucleophilic anilines 2 or N-nucleophilic
anilines 4 leads to 3-(2-hydroxybenzoyl)quinolines and 7H-
chromeno[3,2-c]quinolin-7-ones, respectively. Apparently the
Similar considerations indicate that the reaction of intermedi-
ate 6b with C-nucleophilic anilines 2 and N-nucleophilic anilines
4 should give quinolines 5 and 3, respectively (see Scheme 1
in Supporting Information). This provides an additional argu-
ment in favor of the mechanism shown in Scheme 4.
The composition and structure of all the compounds obtained
1
were determined by LC/MS, elemental analysis, and H and
1
13C NMR and IR spectroscopy. The signals in the H and 13C
NMR spectra were assigned on the basis of 2D NMR techniques
(COSY, NOESY, HMBC, HMQC) of representative com-
pounds. The typical 1H NMR spectrum of quinolines 3 contains
a characteristic set of signals for the protons of ortho-acylated
phenol ring, and two doublets (4JHH ≈ 2.0 Hz) or broadened
singlets for the protons of the pyridine fragment. The signal of
the OH group appears in the range of 10.4-10.6 ppm (DMSO-
(17) Sheldrick, G. M. SHELXTL PLUS, ReV. 5.1; 1998. PC Version. A system
of computer programs for the determination of crystal structure from X-ray
diffraction data.
6012 J. Org. Chem. Vol. 73, No. 15, 2008

1
3
148.8 (dd, JCH ) 181.9 Hz, JCH ) 6.0 Hz, 2-CQn), 158.0 (m,
2-CAr), 167.5 (t, 2JCH ) 3.7 Hz, CONH), 196.4 (m, CdO). IR (KBr),
νmax (cm-1): 3650-3300 (br, OH, NH), 3049, 2995, 2951, 1704
(CdOamide), 1624 (CdO), 1593, 1512, 1462, 1377, 1348, 1304,
1248, 1219, 1159, 1097, 1041, 920, 759. APSI MS: M+ + 1 )
335. Anal. Calcd for C19H14N2O4: C, 68.26; H, 4.22; N, 8.38. Found:
C, 68.42; H, 4.09; N, 8.31.
developed procedure can be applied for the synthesis of diverse
sets of functional drug-like quinolines.
Experimental Section
Preparation of 3-(2-Hydroxyphenyl)quinolines 3a-l and
7H-Chromeno[3,2-c]quinolin-7-ones 5a-o from Anilines
2a-l or 4a-o and 3-formylchromone 1. General Procedure.
Anilines 2a-l or 4a-o (2 mmol) and 3-formylchromone 1 (348
mg, 2 mmol) were placed in a 15-mL pressure tube and dissolved
in DMF (2-4 mL). Chlorotrimethylsilane (652 mg, 3 mmol) was
added dropwise to the solution. The tube was thoroughly sealed
and heated on a water bath (100 °C) for 12-24 h. After cooling
the flask was opened (Caution! ExcessiVe pressure inside), and the
reaction mixture was poured into water (15 mL) and allowed to
stand at 20 °C in an ultrasonic bath for 1 h. The precipitate formed
was filtered and washed with a small amount of i-PrOH. Recrys-
tallization from an appropriate solvent yielded targeted compounds
3a-l and 5a-o. Compounds 3i and 5g were purified by preparative
HPLC.
3-Methyl-2-(2-oxopyrrolidin-1-yl)-7H-chromeno[3,2-c]quino-
1
lin-7-one (5k). Yield 67%; mp 281-282 °C (MeCN). H NMR
3
(500 MHz, DMSO-d6): δ 2.24 (quintet, JH,H ) 6.9 Hz, 2H,
NCH2CH2), 2.42 (s, 3H, CH3), 2.43 (t, 3JH,H ) 6.9 Hz, 2H, COCH2),
3
3
3.90 (t, JH,H ) 6.9 Hz, 2H, NCH2), 7.57 (t, JH,H ) 8.2 Hz, 1H,
3
3
6-HChr), 7.89 (d, JH,H ) 8.2 Hz, 1H, 8-HChr), 7.96 (t, JH,H ) 8.2
Hz, 1H, 7-HChr), 8.04 (s, 1H, 8-HQn), 8.23 (d, 3JH,H ) 8.2 Hz, 1H,
5-HChr), 8.46 (s, 1H, 5-HQn), 9.37 (s, 1H, 2-HQn). 13C NMR (125
MHz, DMSO-d6): δ 18.9 (CH3), 19.4 (NCH2CH2), 31.3 (COCH2),
50.9 (NCH2), 112.6 (3-CChr), 117.2 (4a-CChr), 119.1 (8-CChr), 120.8
(8-CQn), 123.4 (4a-CQn), 126.1 (6-CChr), 126.3 (5-CChr), 131.0 (5-
CQn), 136.2 (7-CChr), 139.3 (6-CQn), 142.5 (7-CQn), 148.7 (2-CQn),
149.2 (8a-CQn), 155.8 (2-CChr), 158.6 (8a-CChr), 174.6 (COCH2),
175.6 (CdO). IR (KBr), νmax (cm-1): 3070, 3041, 2962, 2920, 1682
(CdOamide), 1662 (CdO), 1628, 1614, 1495, 1470, 1446, 1414,
1362, 1294, 1223, 899, 827, 756. APSI MS: M+ + 1 ) 345. Anal.
Calcd for C21H16N2O3: C, 73.24; H, 4.68; N, 8.13. Found: C, 73.08;
H, 4.82; N, 8.21.
8-(2-Hydroxybenzoyl)-2-methyl-2H-[1,4]oxazino[2,3-g]quino-
lin-3(4H)-one (3c). Yield 87%; mp 272-273 °C (EtOH-DMF).
3
1H NMR (500 MHz, DMSO-d6): δ 1.50 (d, JH,H ) 6.6 Hz, 3H,
3
3
CHCH3), 4.92 (q, JH,H ) 6.6 Hz, 1H, CHCH3), 6.98 (t, JH,H
)
8.1 Hz, 1H, 5-HAr), 7.02 (d, 3JH,H ) 8.1 Hz, 1H, 3-HAr), 7.40-7.51
(m, 3H, 4,6-HAr, 5-HQn), 7.53 (s, 1H, 8-HQn), 8.53 (s, 1H, 4-HQn),
8.93 (s, 1H, 2-HQn), 10.38 (br. s, 1H, OH), 11.27 (br. s, 1H, NH).
13C NMR (125 MHz, DMSO-d6): δ 17.0 (qd, JCH ) 129.2 Hz,
1
Acknowledgment. The authors acknowledge Mr. V. V.
Polovinko (“Enamine Ltd.”) and Dr. S. A. Alekseev (Kyiv
National Taras Shevchenko University) for spectral measurements.
2JCH ) 3.7 Hz, CH3), 73.6 (dq, JCH ) 151.2 Hz, JCH ) 4.2 Hz,
1
2
CHCH3), 112.6 (dd, 1JCH ) 164.5 Hz, 3JCH ) 5.0 Hz, 5-CQn), 113.6
1
1
2
(d, JCH ) 164.1 Hz, 8-CQn), 117.6 (dd, JCH ) 161.8 Hz, JCH
)
7.4 Hz, 3-CAr), 119.8 (dd, 1JCH ) 129.2 Hz, 2JCH ) 7.6 Hz, 5-CAr),
Supporting Information Available: Details of the experi-
mental procedures, spectroscopic data of the products, and X-ray
data for the compound 5k in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.
2
2
123.3 (d, JCH ) 5.0 Hz, 3-CQn), 124.7 (m, 1-CAr), 129.7 (d, JCH
2
) 7.3 Hz, 4a-CQn), 130.0 (d, JCH ) 6.8 Hz, 7-CQn), 131.4 (ddd,
1JCH ) 160.3 Hz, 2JCH ) 7.4 Hz, 3JCH ) 1.8 Hz, 6-CAr), 134.4 (dd,
2
1
1JCH ) 160.4 Hz, JCH ) 8.7 Hz, 4-CAr), 137.2 (dt, JCH ) 165.0
3
Hz, JCH ) 5.0 Hz, 4-CQn), 147.1 (m, 6-CQn), 148.4 (m, 8a-CQn),
JO800950Y
J. Org. Chem. Vol. 73, No. 15, 2008 6013