Regioselective synthesis of bioactive spiro heterocyclic compounds containing both indoline and quinolone moieties by aryl radical cyclization

Article abstract of DOI:10.1002/jhet.101

(Chemical Equation Presented) The tin hydride-mediated aryl radical cyclization of a number of 4-(2′-bromo-N-methylanilino)-methyl-1- alkylquinolin-2(1H)-ones under mild neutral condition afforded 1-alkyl-3,4-dihydroquinolin-2(1H)-one-4-spiro-3′-(1-methyl

Full text of DOI:10.1002/jhet.101

492
Regioselective Synthesis of Bioactive Spiro Heterocyclic
Compounds Containing Both Indoline and Quinolone
Moieties by Aryl Radical Cyclization
Vol 46
K. C. Majumdar* and N. Kundu
Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
*E-mail: kcm_ku@yahoo.co.in
Received April 29, 2008
DOI 10.1002/jhet.101
Published online 26 May 2009 in Wiley InterScience (www.interscience.wiley.com).
The tin hydride-mediated aryl radical cyclization of a number of 4-(20-bromo-N-methylanilino)-
methyl-1-alkylquinolin-2(1H)-ones under mild neutral condition afforded 1-alkyl-3,4-dihydroquinolin-
2(1H)-one-4-spiro-30-(1-methylindolines) in excellent yield. The starting materials, amines were derived
from 4-bromomethyl-N-methyl quinolin-2(1H)-ones and 2-bromo-N-methyl anilines by refluxing in ace-
tone in the presence of anhydrous potassium carbonate and sodium iodide (Finkelstein condition).
J. Heterocyclic Chem., 46, 492 (2009).
INTRODUCTION
attached at the b-carbon of an a,b-unsaturated lactone
system. Stabilization of the intermediate radical by the
carbonyl group controls this regioselectivity [35]. It is
also well documented that a 5-hexenyl radical cyclizes
preferentially to the cyclopentylmethyl radical via 5-exo
cyclization and not to the more stable cyclohexyl radical
via 6-endo cyclization [36,37]. In this context, we under-
took a study on the radical cyclizations of 4-(20-bromo-N-
methylanilinomethyl)-1-alkylquinolin-2(1H)-ones where
these very criteria are present. Also quinolones fused
with other heterocycles are known to have interesting bi-
ological activities and medicinal properties. Quinolone
derivatives are biologically significant [38–42] because of
their antibacterial activity, DNA-gyrase inhibition and
marked cytotoxicity against animal and plant tumors.
Keeping these biological activities in mind a number of
attempts have been made over the last few decades to
synthesize various biologically active quinolone deriva-
tives many of which are abundant in nature [43]. Herein,
we report the regioselective formation of spiro quinolone
Nitrogen-containing heterocycles as recognized phar-
macophores have received great attention in drug dis-
covery and lead optimization [1–3]. In addition to tradi-
tional cycloadditions, cyclizations of nitrogen radicals or
nitrogen-containing carbon radicals are the new
approaches to N-heterocyclics [4–11]. Between these
two radical reactions, the latter one is more general
because carbon radicals are easy to generate and car-
bon–carbon bond formation by radical cyclization is a
well-established process [12–16]. In our continuous
effort on the development of free-radical reactions, we
recently reported the 5-exo cyclization [17–20] and 6-
endo cyclization [21,22] of oxygen heterocycles. We
also recently reported the cyclization of 4-(20-bromo-
n
thioarylmethyl)-1-methylquinolin-2(1H)-one by Bu3SnH
and AIBN, where a 6-endo ring closure took place to
generate a six-membered sulfur heterocycle [23]. Sev-
eral methodologies based on free-radical cyclization for
the construction of five- [24–26] and six-membered [27–
31] nitrogen heterocycles are available. In contrast, for-
mation of spiro nitrogen heterocycles is almost rarely
reported in literature [32–34].
n
heterocycles by Bu3SnH mediated radical cyclization.
RESULTS AND DISCUSSION
Zhang and Pugh [35] demonstrated that intramolecu-
lar free-radical Michael-type addition facilitates the
spiro cyclization process when an aryl radical is
The amines 3a–f required for the present study were
readily prepared in 89–95% yield from o-bromoanilines
C
V
2009 HeteroCorporation

May 2009
Regioselective Synthesis of Bioactive Spiro Heterocyclic Compounds Containing
both Indoline and Quinolone Moieties by Aryl Radical Cyclization
493
Scheme 1. Reagents and conditions: (i) Acetone, K2CO3, NaI, reflux,
n
ene protons resonance at d 2.83 and 2.90 (CH2CO) are
related with carbon resonance at d 42.34 and the meth-
ylene protons at d 3.21 and 3.39 (AN(CH3)CH2) are
related with carbon resonance at d 67.42 respectively.
Mass spectrum of the compound 4a showed a molecular
ion peak at m/z ¼ 293 (Mþ þ 1). These clearly indi-
cated the formation of a spiro heterocyclic compound.
The other substrates 3b–f were also treated similarly
to afford exclusively compounds 4b–f in 90–95% yield.
FMO theory can rationalize the regioselective forma-
tion of the spiro heterocyclic ring. Aryl radicals are high
energy species and hence are nucleophilic in character.
The highly electron withdrawing carbonyl group confers
considerable electrophilic character to the C-4 position
of the quinolone moiety. Thus in the case of nucleo-
philic radical 5, FMO theory suggests that the mode of
ring closure is largely determined by the interaction
between the radical SOMO (:HOMO) and the alkene
LUMO of the acceptor (electron deficient centre) and
accordingly more favorable bond formation occurs
between the radical centre (nucleophilic) and C-4 of the
quinolone ring for 5-exo product 4a–f (Scheme 2) con-
taining both the quinolone and indoline moieties which
are known to be present in biologically active
compounds.
8h; (ii) Bu3SnH, toluene, 80ꢀC N2 atm, 1h.
In conclusion, we can say that the exclusive formation
of 5-membered spiro heterocyclic pyrrole ring in excel-
lent yield occurs because of two driving forces: first, the
stabilization of the radical intermediate and second, ster-
eoelectronically favored 5-exo pathway. This gives a
simple and straightforward synthesis for spiro heterocy-
clic compounds. The methodology described here is
mild and attractive because of its simplicity.
2a–c and 4-bromomethyl-1-alkylquinolin-2(1H)-ones
1a,b in refluxing acetone for 8 h in the presence of an-
hydrous potassium carbonate and sodium iodide. The
n
amines were subjected to Bu3SnH-AIBN induced radi-
cal cyclization. Compound 3a when heated at 80ꢀC in
dry degassed toluene under nitrogen with nBu3SnH in
the presence of catalytic amount of AIBN for 1 h
afforded the cyclic product 4a in 90% yield (Scheme 1).
The structure of the compound 4a was readily confirmed
by 1H NMR spectroscopy which exhibited one proton
doublet at d 2.83 (J ¼ 16 Hz), another one proton dou-
blet at d 2.90 (J ¼ 16 Hz) due to ACOCH2,
AN(CH3)CH2 protons appear as two one proton doublet
each at d 3.21 and 3.39 (J ¼ 8.8 Hz). Further confirma-
tion of the structure 4a came from its COSY, HETCOR
and 13C NMR spectrum. COSY spectrum of compound
4a showed that ACOCH2 protons at d 2.83 and 2.90
correlate with each other and AN(CH3)CH2 protons at d
3.21 and 3.39 correlate with each other. The 13C NMR
spectrum of 4a also strongly supported its structure. The
13C chemical shifts of the compound 4a are assigned by
DEPT experiment. DEPT showed thirteen protonated
carbons, two ACH3, three >CH2 and eight >CHA moi-
eties. Protonated carbon resonances are established by
direct correlation with proton resonance by HETCOR
experiment (normal one bond CAH coupling). Methyl-
EXPERIMENTAL
Melting points were determined in an open capillary and are
uncorrected. IR spectra were recorded on a Perkin–Elmer L
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

494
K. C. Majumdar and N. Kundu
Vol 46
120-000A spectrometer (mmax in cmꢁ1) using samples as neat
liquids and solid samples were recorded on KBr disks. UV
absorption spectra were recorded in EtOH on a Shimadzu UV-
1590 (C¼¼C) cmꢁ1; UV (EtOH) kmax(log e): 215 (4.73), 229
(4.77), 330 (3.96) nm; 1H NMR (400 MHz, CDCl3): dH 2.75
(s, 3H, CH2NCH3), 3.74 (s, 3H, CONCH3), 4.35 (s, 2H,
NCH2), 6.91–6.95 (m, 1H, ArH), 7.03 (s, 1H, ¼¼CH), 7.19–
7.85 (m, 7H, ArH); MS (m/z): 381 (Mþ þ 23, 21%), 379 (Mþ
þ 23, 26%), 359 (Mþ þ 1, 96%), 357 (Mþ þ 1, 89%), 309
(100%), 277 (31%). Anal. Calcd for C18H17BrN2O: C, 60.51;
H, 4.79; N, 7.84%. Found: C, 60.76; H, 4.68; N, 7.65%.
Compound (3e). Yield 92%, White solid, mp 100–102ꢀC;
IR (KBr) tmax: 2922 (Aromatic CH stretching), 1654 (CO d
lactum), 1588 (C¼¼C) cmꢁ1; UV (EtOH) kmax(log e): 218
(4.63), 230 (4.66), 330 (3.85) nm; 1H NMR (500 MHz,
CDCl3): dH 2.29 (s, 3H, ArCH3), 2.73 (s, 3H, CH2NCH3), 3.73
(s, 3H, CONCH3), 4.32 (s, 2H, NCH2), 7.00 (s, 1H, ¼¼CH),
7.07–7.89 (m, 7H, ArH); MS (m/z): 395 (Mþ þ 23, 21%), 393
(Mþ þ 23, 21%), 373 (Mþ þ 1, 89%), 371 (Mþ þ 1, 100%),
291 (17%). Anal. Calcd for C19H19BrN2O: C, 61.46; H, 5.15;
N, 7.54%. Found: C, 61.68; H, 5.30; N, 7.31%.
1
2401PC spectrophotometer (kmax in nm). H NMR (400 MHz,
500 MHz) and 13C NMR (125 MHz) spectra were recorded on
a Bruker DPX-400 and Bruker DPX-500 spectrometer in
CDCl3 (chemical shift in d) with TMS as internal standard.
Elemental analyses and mass spectra were recorded on a Leco
932 CHNS analyzer and on a JEOL JMS-600 instrument
respectively. Silica gel [60–120 mesh, Spectrochem, India]
was used for chromatographic separation. Silica gel G [E-
Merck, India] was used for TLC. Petroleum ether refers to the
fraction boiling between 60 and 80ꢀC.
General procedure for the preparation of 4-(20-bromo-N-
methylanilino)methyl-1-alkylquinolin-2(1H)-ones 3a–f. A
mixture of 4-bromomethyl-N-alkylquinolone (1a,b,5 mmol), 2-
bromoaniline (2a–f, 5 mmol), anhydrous potassium carbonate
(5 g) and sodium iodide (20 mg) was heated under reflux in
dry acetone (125 mL) for 8 h. The reaction mixture was
cooled, filtered and concentrated. The residual mass was
extracted with CH2Cl2(3 ꢂ 50 mL), washed with 10%
Na2CO3 solution (2 ꢂ 25 mL), brine (3 ꢂ 50 mL) and dried
(Na2SO4). The residual mass after the removal of solvent was
subjected to column chromatography on silica gel using petro-
leum ether EtOAc (4:1) as eluant to give compounds 3a–f
which were recrystallized from CHCl3-petroleum ether.
Compound (3f). Yield 92%, White solid, mp 101–102ꢀC;
IR (KBr) tmax: 2922 (Aromatic CH stretching), 1651 (CO d
lactum), 1591 (C[dond]C) cmꢁ1; UV (EtOH) kmax (log e): 215
(4.45), 232 (4.48), 330 (3.87) nm; 1H NMR (500 MHz,
CDCl3): dH 1.19 (t, J ¼ 7.5 Hz, 3H, ArCH2CH3), 2.55 (q, J ¼
7.5 Hz, 2H, ArCH2CH3), 2.72 (s, 3H, CH2NCH3), 3.72 (s, 3H,
CONCH3), 4.31 (s, 2H, NCH2), 7.01 (s, 1H, ¼¼CH), 7.09–7.88
(m, 7H, ArH); MS (m/z): 409 (Mþ þ 23, 14%), 407 (Mþ
þ
Compound (3a). Yield 95%, Viscous liquid; IR (Neat) tmax
:
23, 14%), 387 (Mþ þ 1, 100%), 385 (Mþ þ 1, 85%), 305
(11%); Anal. Calcd for C20H21BrN2O: C, 62.34; H, 5.49; N,
7.27%. Found: C, 62.08; H, 5.71; N, 7.11%.
2922 (Aromatic CH stretching), 1652 (CO d lactum), 1590
(C¼¼C) cmꢁ1; UV (EtOH) kmax(log e): 213 (4.44), 232 (4.49),
1
329 (3.76) nm; H NMR (400 MHz, CDCl3): dH 1.35 (t, J ¼
General procedure for the preparation of 1-alkyl-3,
4-dihydroquinolin-2(1H)-one-4-spiro-30-(1-methylindoline)
4a–f. Tributyltin hydride (1.1 mmol) was added to a stirred
solution of (3a–f, 1 mmol) and azobisisobutyronitrile (0.5
mmol) in dry degassed toluene (5 mL) under nitrogen. The
mixture was heated at 80ꢀC for 1 h and concentrated. The resi-
due was dissolved in ether (10 mL) and stirred with a 10% aq.
potassium fluoride solution (10 mL) for 45 min. The white
precipitate was filtered and the aqueous phase was extracted
with ether (10 mL). The combined ether extract was washed
with brine and dried (Na2SO4). The residual mass after the re-
moval of solvent was subjected to column chromatography
using petroleum ether-ethyl acetate (4:1) as eluant to give
cyclized product 4a–f.
7.1 Hz, 3H, NCH2CH3), 2.75 (s, 3H, NCH3), 4.35 (s, 2H,
CH2NCH3), 4.36 (q, J ¼ 7.1 Hz, 2H, NCH2CH3), 6.91–6.96
(m, 1H, ArH), 7.04 (s, 1H, ¼¼CH), 7.17–7.85 (m, 7H, ArH);
MS (m/z): 395 (Mþ þ 23, 20%), 393 (Mþ þ 23, 20%), 373
(Mþ þ 1, 91%), 371 (Mþ þ 1, 100%), 291 (15%). Anal.
Calcd for C19H19BrN2O: C, 61.46; H, 5.15; N, 7.54%. Found:
C, 61.75; H, 4.95; N, 7.42%.
Compound (3b). Yield 90%, Viscous liquid; IR (Neat) tmax
:
2920 (Aromatic CH stretching), 1652 (CO d lactum), 1591
(C¼¼C) cmꢁ1; UV (EtOH) kmax(log e): 214 (4.36), 330 (3.51)
1
nm; H NMR (500 MHz, CDCl3): dH 1.36 (t, J ¼ 7.1 Hz, 3H,
NCH2CH3), 2.29 (s, 3H, ArCH3), 2.73 (s, 3H, CH2NCH3),
4.32 (s, 2H, CH2NCH3), 4.36 (q, J ¼ 7.1 Hz, 2H, NCH2CH3),
7.02 (s, 1H, ¼¼CH), 7.08–7.91 (m, 7H, ArH); MS (m/z): 409
(Mþ þ 23, 22%), 407 (Mþ þ 23, 21%), 387 (Mþ þ 1, 100%),
Compound (4a). Yield 90%, Viscous liquid; IR (Neat) tmax
:
2974 (Aromatic CH stretching), 1673 (CO d lactum) cmꢁ1; UV
385 (Mþ
þ
1, 92%), 305 (15%). Anal. Calcd for
(EtOH) kmax (log e): 212 (4.47), 253 (4.19), 305 (3.42) nm; H
1
C20H21BrN2O: C, 62.34; H, 5.49; N, 7.27%. Found: C, 62.12;
H, 5.68; N, 7.15%.
NMR (500 MHz, CDCl3): dH 1.28 (t, J ¼ 7.1 Hz, 3H,
NCH2CH3), 2.75 (s, 3H, NCH3), 2.83 (d, J ¼ 16 Hz, 1H,
COCH), 2.90 (d, J ¼ 16 Hz, 1H, COCH), 3.21 (d, J ¼ 8.8 Hz,
1H, NCH), 3.39 (d, J ¼ 8.8 Hz, 1H, NCH), 4.03 (q, J ¼ 7.1 Hz,
2H, NCH2CH3), 6.59–7.25 (m, 8H, ArH); 13C NMR (125 MHz,
CDCl3): dC 12.70 (NCH2CH3), 35.52 (NCH3), 37.16
(NCH2CH3), 42.34 (COCH2), 46.55 (CH2C), 67.42 (CH2NCH3),
107.85 (ArCH), 115.02 (ArCH), 118.41 (ArCH), 123.09 (ArCH),
123.52 (ArCH), 127.00 (ArCH), 128.02 (ArCH), 128.82 (ArCH),
131.93 (ArC), 132.55 (ArC), 138.65 (ArC), 153.04 (ArC), 168.05
(CO); MS (m/z): 315 (Mþ þ 23, 25%), 293 (Mþ þ 1, 100%),
289 (20%), 251 (50%). Anal. Calcd for C19H20N2O: C, 78.05; H,
6.89; N, 9.54%. Found: C, 77.90; H, 6.63; N, 9.80%.
Compound (3c). Yield 89%, Viscous liquid; IR (Neat) tmax
:
2922 (Aromatic CH stretching), 1652 (CO d lactum), 1592
(C¼¼C) cmꢁ1; UV (EtOH) kmax(log e): 215 (3.62), 231 (3.67),
330 (2.83) nm; 1H NMR (500 MHz, CDCl3): dH 1.19 (t, J ¼ 7.5
Hz, 3H, ArCH2CH3), 1.35 (t, J ¼ 7.1 Hz, 3H, NCH2CH3), 2.55
(q, J ¼ 7.5 Hz, 2H, ArCH2CH3), 2.72 (s, 3H, NCH3), 4.31 (s,
2H, CH2NCH3), 4.34 (q, J ¼ 7.1 Hz, 2H, NCH2CH3), 7.01 (s,
1H, ¼¼CH), 7.09–7.89 (m, 7H, ArH); MS (m/z): 401 (Mþ þ 1,
100%), 399 (Mþ þ 1, 86%), 319 (7%), 317 (17%), 309 (57%),
293 (25%). Anal. Calcd for C21H23BrN2O: C, 63.16; H, 5.80; N,
7.01%. Found: C, 63.28; H, 6.03; N, 7.20%.
Compound (3d). Yield 95%, Viscous liquid;. IR (Neat)
max: 2924 (Aromatic CH stretching), 1656 (CO d lactum),
Compound (4b). Yield 95%, White solid, mp 124–126ꢀC;
IR (KBr) tmax: 2921 (Aromatic CH stretching), 1674 (CO d
t
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2009
Regioselective Synthesis of Bioactive Spiro Heterocyclic Compounds Containing
both Indoline and Quinolone Moieties by Aryl Radical Cyclization
495
lactum) cmꢁ1; UV (EtOH) kmax (log e): 211 (4.51), 253
(4.18), 313 (3.34) nm; H NMR (500 MHz, CDCl3,): dH 1.28
Acknowledgment. This work was supported by CSIR, New
Delhi. N. Kundu thanks CSIR for a Senior Research Fellowship.
1
(t, J ¼ 7.1 Hz, 3H, NCH2CH3), 2.26 (s, 3H, ArCH3), 2.71 (s,
3H, NCH3), 2.82 (d, J ¼ 16 Hz, 1H, COCH), 2.90 (d, J ¼ 16
Hz, 1H, COCH), 3.18 (d, J ¼ 8.8 Hz, 1H, NCH), 3.33 (d, J ¼
8.8 Hz, 1H, NCH), 4.01 (q, J ¼ 7.1 Hz, 2H, NCH2CH3),
6.51–7.29 (m, 7H, ArH); MS (m/z): 329 (Mþ þ 23, 50%), 307
(Mþ þ 1, 100%), 303 (11%), 265 (39%). Anal. Calcd for
C20H22N2O: C, 78.39; H, 7.23; N, 9.14%. Found: C, 78.60; H,
7.04; N, 9.02%.
REFERENCES AND NOTES.
[1] Balkenhohl, F.; von dem Bussche-Hunnefeld, C.; Lansky,
A.; Zechel, C. Angew Chem Int Ed Engl 1996, 35, 2288.
[2] Nefzi, A.; Ostresh, J. M.; Houghten, R. A. Chem Rev 1997,
97, 449.
[3] Loughlin, W. A. Aust J Chem 1998, 51, 875.
[4] Stella, L. Radicals in Organic Synthesis; Renaud, P.; Sibi,
M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2, p 407.
[5] Maxwell, B. J.; Tsanaktsidis, J. In N-Centered Radicals;
Alfasi, Z. B., Ed.; Wiley: New York, 1980; Chapter 3, p 151.
[6] Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53, 17543.
[7] Hart, D. J. Radicals in Organic Synthesis; Renaud, P.; Sibi,
M. P.,, Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2, p 276.
[8] Bowman, W. R.; Cloonan, M. O.; Krintel, S. L. J Chem
Soc Perkin Trans 1 2001, 2885.
Compound (4c). Yield 92%, Viscous liquid; IR (Neat) tmax
:
;
2926 (Aromatic CH stretching), 1676 (CO d lactum) cmꢁ1
UV (EtOH) kmax (log e): 211 (3.85), 253 (3.57), 312 (3.37)
1
nm; H NMR (400 MHz, CDCl3): dH 1.15 (t, J ¼ 7.5 Hz, 3H,
ArCH2CH3), 1.27 (t, J ¼ 7.1 Hz, 3H, NCH2CH3), 2.52 (q, J ¼
7.5 Hz, 2H, ArCH2CH3), 2.71 (s, 3H, NCH3), 2.82 (d, J ¼ 16
Hz, 1H, COCH), 2.90 (d, J ¼ 16 Hz, 1H, COCH), 3.17 (d, J
¼ 8.8 Hz, 1H, NCH), 3.33 (d, J ¼ 8.8 Hz, 1H, NCH), 3.99 (q,
J ¼ 7.1 Hz, 2H, NCH2CH3), 6.52–7.29 (m, 7H, ArH); MS (m/
z): 343 (Mþ þ 23, 14%), 321 (Mþ þ 1, 84%), 317 (100%),
289 (38%), 279 (27%). Anal. Calcd for C21H24N2O: C, 78.71;
H, 7.54; N, 8.74%. Found: C, 78.48; H, 7.69; N, 8.90%.
[9] Aldabbagh, F.; Bowman, W. R. Contemp Org Synth 1997,
4, 261.
[10] Kappe, T. H.; Kappe, C. O. Progress in Heterocyclic
Chemistry; Suschitzky, H.; Gribble, G., Eds.; Elsevier: New York,
1996; Vol. 8.
Compound (4d). Yield 95%, White solid, mp 120–122ꢀC; IR
(KBr) tmax: 2952 (Aromatic CH stretching), 1676 (CO d lac-
tum) cmꢁ1; UV (EtOH) kmax (log e): 211 (4.72), 251 (4.19),
[11] Ishibashi, H.; Sato, T.; Ikeda, M. Synthesis 2002, 695.
[12] Giese, B. Radicals in Organic Synthesis: Formation of C-C
Bonds; Pergamon: Oxford, 1986.
1
305 (3.40) nm; H NMR (400 MHz, CDCl3): dH 2.74 (s, 3H,
CH2NCH3), 2.85 (d, J ¼ 16 Hz, 1H, COCH), 2.90 (d, J ¼ 16
Hz, 1H, COCH), 3.21 (d, J ¼ 8.8 Hz, 1H, NCH), 3.40 (d, J ¼
8.8 Hz, 1H, NCH), 3.42 (s, 3H, CONCH3), 6.58–7.30 (m, 8H,
ArH); MS (m/z): 301 (Mþ þ 23, 20%), 279 (Mþ þ 1, 100%),
375 (25%), 237 (17%). Anal. Calcd for C18H18N2O: C, 77.66;
H, 6.51; N, 10.06%. Found: C, 77.90; H, 6.35; N, 9.86%.
[13] Curran, D. P. Synthesis 1988, 417.
[14] Curran, D. P. Comprehensive Organic Synthesis; Trost, B.
M.; Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, Chapters 4.1
and 4.2.
[15] Motherwell, W. B.; Crich, D. Best Synthetic Methods, Free
Radical Chain Reactions in Organic Synthesis; Academic Press:
London, 1991.
Compound (4e). Yield 92%, White solid, mp 99–101ꢀC; IR
(KBr) tmax: 2988 (Aromatic CH stretching), 1676 (CO d lac-
tum) cmꢁ1; UV (EtOH) kmax (log e): 211 (4.51), 253 (4.14),
[16] Giese, B.; Kopping, B.; Gobel, T.; Dickhaut, J.; Thoma, G.;
Kulicke, K. J.; Trach, F. Org React 1996, 48, 301.
[17] Majumdar, K. C.; Mukhopadhyay, P. P.; Basu, P. K. Synth
Commun 2005, 35, 1291.
1
313 (3.36) nm; H NMR (500 MHz, CDCl3): dH 2.26 (s, 3H,
ArCH3), 2.72 (s, 3H, CH2NCH3), 2.86 (d, J ¼ 16 Hz, 1H,
COCH), 2.90 (d, J ¼ 16 Hz, 1H, COCH), 3.20 (d, J ¼ 8.8 Hz,
1H, NCH), 3.35 (d, J ¼ 8.8 Hz, 1H, NCH), 3.44 (s, 3H,
[18] Majumdar, K. C.; Mukhopadhyay, P. P. Synthesis 2004,
1864.
CONCH3), 6.52–7.28 (m, 7H, ArH); MS (m/z): 315 (Mþ
þ
[19] Majumdar, K. C.; Chattopadhyay, S. K. Tetrahedron Lett
2004, 45, 6871.
23, 14%), 293 (Mþ þ 1, 100%), 289 (21%), 251 (50%). Anal.
Calcd for C19H20N2O: C, 78.05; H, 6.89; N, 9.58%. Found: C,
77.78; H, 7.08; N, 9.43%.
[20] Majumdar, K. C.; Kundu, N. Synth Commun 2006, 36,
1879.
[21] Majumdar, K. C.; Basu, P. K.; Mukhopadhyay, P. P.; Sar-
kar, S.; Ghosh, S. K.; Biswas, P. Tetrahedron 2003, 59, 2151.
[22] Majumdar, K. C.; Mukhopadhyay, P. P. Synthesis 2003, 97.
[23] Majumdar, K. C.; Kundu, N. Synth Commun 2007, 37, 1747.
[24] Sato, T.; Nakamura, N.; Ikeda, K.; Okada, M.; Ishibashi,
H.; Ikeda, M. J Chem Soc Perkin Trans 1 1992, 2399.
[25] Parsons, A. F.; Williams, D. A. J. Tetrahedron 2000, 56,
7217.
Compound (4f). Yield 90%, Viscous liquid, IR (Neat) tmax
:
;
2917 (Aromatic CH stretching), 1674 (CO d lactum) cmꢁ1
UV (EtOH) kmax (log e): 214 (4.32), 254 (4.11), 311 (3.40)
1
nm; H NMR (500 MHz, CDCl3): dH 1.15 (t, J ¼ 7.5 Hz, 3H,
ArCH2CH3), 2.52 (q, J ¼ 7.5 Hz, 2H, ArCH2CH3), 2.71 (s,
3H, CH2NCH3), 2.85 (d, J ¼ 16 Hz, 1H, COCH), 2.90 (d, J ¼
16 Hz, 1H, COCH), 3.18 (d, J ¼ 8.8 Hz, 1H, NCH), 3.35 (d, J
¼ 8.8 Hz, 1H, NCH), 3.42 (s, 3H, CONCH3), 6.53–7.30 (m,
7H, ArH); 13C NMR (125 MHz, CDCl3): dC 15.41
(ArCH2CH3), 27.75 (ArCH2CH3), 28.92 (CH2NCH3), 35.49
(CONCH3), 41.54 (COCH2), 46.00 (CH2C), 67.44 (CH2NCH3),
107.41 (ArCH), 114.46 (ArCH), 122.47 (ArCH), 122.67
(ArCH), 126.24 (ArCH), 127.42 (ArCH), 127.51 (ArCH),
131.04 (ArC), 132.14 (ArC), 134.13 (ArC), 139.27 (ArC),
150.72 (ArC), 168.21 (CO); MS (m/z): 329 (Mþ þ 23, 18%),
307 (Mþ þ 1, 100%), 303 (50%), 265 (50%). Anal. Calcd for
C20H22N2O: C, 78.39; H, 7.23; N, 9.14%. Found: C, 78.21; H,
7.45; N, 8.96%.
[26] Ishibashi, H.; Ohata, K.; Niihara, M.; Sato, T.; Ikeda, M.
J Chem Soc Perkin Trans 1 2000, 547.
[27] Ryu, I.; Ogura, S.; Minakata, S.; Komatsu, M. Tetrahehron
Lett 1999, 40, 1515.
[28] Harrowven, D. C.; Sutton, B. J.; Coulton, S. Tetrahedron
2002, 58, 3387.
[29] Todd, M. H.; Ndubaku, C.; Bartlett, P. A. J Org Chem
2002, 67, 3985.
[30] Majumdar, K. C.; Mukhopadhyay, P. P. Synthesis 2003,
920.
[31] Majumdar, K. C.; Sarkar, S. Synth Commun 2004, 34,
2873.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

496
K. C. Majumdar and N. Kundu
Vol 46
[32] Escolanco, C.; Jones, K. Tetrahedron Lett 2000, 41, 8951.
[39] Laborde, E.; Kiely, J. S.; Culbertson, T. P.; Lesheski, L. E.
J Med Chem 1993, 36, 1964.
´
[40] Gozalbes, R.; Brun-pascaud, M.; Garcıa-Domenech, R.;
[33] Escolanco, C.; Jones, K. Tetrahedron 2002, 58, 1453.
[34] Flanagan, S. R.; Harrowven, D. C.; Bradley, M. Tetraheh-
ron Lett 2003, 44, 1795.
´
Galvez, J.; Girard, P.; Doucet, J.; Derouin, F. Antimicrob Agents Che-
mother 2000, 44, 2764.
[35] Zhang, W.; Pugh, G. Tetrahedron Lett 2001, 42, 5617.
[36] Beckwith, A. L. J.; Ingold, K. U. Rearrangement in Ground
and Excited States; de Mayo, P., Ed.; Academic Press: New York,
1980; Vol. 1, p 161.
[41] Lawrence, L. E.; Wu, P.; Fan, L.; Gouveia, K. E.; Card, A.;
Casperson, M.; Denbleyker, K.; Barrett, J. F. J Antimicrob Chemother
2001, 48, 195.
[37] Beckwith, A. L. J. Tetrahedron 1981, 37, 3073.
[38] Hagen, S. E.; Domagala, J. M.; Heifetz, C. L.; Sanchez, J.
P.; Solomon, M. J Med Chem 1990, 33, 849.
[42] Neville, C. F.; Grundon, M. F.; Ramchandran, V. N.;
Reisch, G.; Reisch, J. J Chem Soc Perkin Trans 1 1991, 2261.
[43] Jurd, L.; Benson, M. J Chem Soc Chem Commun 1983, 92.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet