Electrosynthesis of 3-chloro-1,4-disubstituted-2(1H)-quinolinones and 3,3-dichloro-4-hydroxy-1,4-disubstituted-3,4-dihydro-2(1H)-quinolinones, as well as a new convenient process to dioxindoles

Article abstract of DOI:10.1021/jo0267403

Cathodic reduction of N-(2-acyl(or aroyl)phenyl)-2,2,2,-trichloro-N-alkylacetamide at - 1.2 V (vs SCE) under aprotic conditions yields 3-chloro-1,4-disubstituted-2(1H)-quinolinones (1) as the major product. When the reaction is carried out at -0.8 V (vs S

Full text of DOI:10.1021/jo0267403

quinolinones have been prepared by using the Vilsmaier
reagent,11-13 and 3,3-dichloro-4-aryl-N-substituted-3,4-
dihydro-2(1H)-quinolone synthesis involves cyclization of
â-keto amides in H2SO4.14
Dioxindoles are recognized antihypoxic compounds but
their biological activity has been evaluated only as
racemates.15 Dioxindol derivatives are encountered in
nature and were isolated from the culture of a marine
Streptomyces species.16 Dioxindoles can be obtained by
Grignard reaction on isatines17 and by oxidation of 1,3-
disubstituted-2-indolinones.18 Enantiomerically pure di-
oxindoles can be obtained via catalytic hydrogenations
of isatine derivatives.19
Electr osyn th esis of
3-Ch lor o-1,4-d isu bstitu ted -2(1H)-
qu in olin on es a n d
3,3-Dich lor o-4-h yd r oxy-1,4-d isu bstitu ted -
3,4-d ih yd r o-2(1H)-qu in olin on es, a s Well a s a
New Con ven ien t P r ocess to Dioxin d oles†
Bele´n Batanero and Fructuoso Barba*
Department of Organic Chemistry, University of Alcala´,
28871 Alcala´ de Henares (Madrid), Spain
fructuoso.barba@uah.es
Received November 20, 2002
In the present paper an easy methodology to prepare
1-alkyl-4-alkyl(or phenyl)-3-chloro-2(1H)-quinolinones and
1-alkyl-4-alkyl(or phenyl)-3,3-dichloro-4-hydroxy-3,4-di-
hydro-2(1H)-quinolinones, as well as a simple process to
dioxindole derivatives by using N-alkyl-acetamides as
starting material, is described.
The electroactive substrates were obtained by N-
alkylations of 2-aminophenones prior to acylations with
trichloroacetic acid chloride.20 Methyl, ethyl, and isopro-
pyl iodides were used as alkylating agents.
Cyclic voltammograms (scan rate: 0.1 V/s) of N-(2-acyl-
(or aroyl)phenyl)-N-alkylacetamides exhibit two irrevers-
ible 1e- (-0.8 V) and 2e- (-0.9 V vs SCE) peaks. Cathodic
reduction of these substrates, in dry acetonitrile/LiClO4
with mercury as a cathode at a constant potential of -1.2
V vs SCE, affords 1-alkyl-3-chloro-4-methyl(or phenyl)-
1H-quinolin-2-ones (1) in good yield (70-82%). Coulom-
metry under these potential conditions confirms a 3e-
process.
Abstr a ct: Cathodic reduction of N-(2-acyl(or aroyl)phenyl)-
2,2,2,-trichloro-N-alkylacetamide at -1.2 V (vs SCE) under
aprotic conditions yields 3-chloro-1,4-disubstituted-2(1H)-
quinolinones (1) as the major product. When the reaction is
carried out at -0.8 V (vs SCE), 3,3-dichloro-4-hydroxy-1,4-
disubstituted-3,4-dihydro-2(1H)-quinolinones (2) and 1,4-
disubstituted-1,4-dihydro-quinoline-2,3-dione (3) are formed.
Ring contraction of 2 and 3 in aqueous sodium hydroxide
resulted in the formation of 3-hydroxy-1,3-dihydroindol-2-
ones (5). The most plausible reaction mechanisms are
proposed.
Cathodic reduction of R-halocarbonyl substrates has
been demonstrated to be a useful procedure to synthesize
heterocyclic compounds.1
Quinolin-2-one derivatives have been paid considerable
attention in organic chemistry due to their use as
antiinflammatories, antihypertensives, and analgesics2
or in the preparation of antipsychotic agents.3 3-Halo-
2(1H)-quinolinones have been used as cardiac stimulants4
and as herbicides.5 The 3,3-dihalo-3,4-dihydroquinolin-
2,4-diones have shown antiinflamatory activity6 and
N-substituted 3-arylquinolin-2,4-diones are natural al-
kaloid precursors;7 in addition 3-aryl-4-hydroxyquinolin-
2(1H)-ones have recently been found8 to serve as key
intermediates in the synthesis of non-peptide GnRH
receptor antagonists.
Preparative scale electrolyses at the first peak poten-
tial were performed. However, due to the vicinity of the
second peak, the charge consumption at the end of the
(10) ] De Angelis, F.; Inesi, A.; Feroci, M.; Nicoletti, R. J . Org. Chem.
1995, 60, 445.
(11) ] Chupp, J . P.; Metz, S. J . Heterocycl. Chem. 1979, 16, 65.
(12) ] Hayes, R.; Meth-Cohn, O.; Tarnowski, B. J . Chem. Res. Synop.
1980, 414.
(13) ] Andreani, A.; Bonazzi, D.; Rambaldi, M. Boll. Chim. Farm.
1976, 115, 732.
(14) ] Staskun, B. J . Org. Chem. 1980, 45, 2482. Marais, J . L. C.;
Staskun, B. J . Org. Chem. 1985, 50, 4652.
Some described synthetic procedures to produce 3-chlo-
ro-1,4-dialkyl-2(1H)-quinolones involve halocarbene in-
termediates.9,10 However, 3-halo-N-substituted-2(1H)-
(15) ] Mazhilis, L. I.; Garalene, V. N.; Stankyavichyus, A. P.;
Risyalis, S. P. Khim. Farmat. Zh. 1985, 19, 960.
(16) ] Tang, Y.-Q.; Sattler, I.; Thiericke, R.; Grabley, S.; Feng, X.-Z.
Eur. J . Org. Chem. 2001, 261-267. Balk-Bindseil, W.; Helmke, E.;
Weyland, H.; Laatsch, H. Liebigs Ann. Chem. 1995, 1291-1294.
(17) ] Ogata, M.; Matsumoto, H.; Tawara, K. Eur. J . Med. Chem.
Chim. Ther. 1981, 16, 373-379. Wierenga, W.; Griffin, J .; Warpehoski,
M. A. Tetrahedron Lett. 1983, 24, 2437-2440.
(18) ] Nishio, T. J . Chem. Soc., Perkin Trans. 1 1991, 1717-1720.
(19) ] Carpentier, J .-F.; Mortreux, A. Tetrahedron: Asymmetry 1997,
8, 1083-1099.
† Dedicated to Prof. Hans J . Scha¨fer on the occasion of his 65th
birthday.
(1) ] (a) Barba, F.; Batanero, B. J . Org. Chem. 1993, 58, 6889. (b)
Barba, F.; de la Fuente, J . L. J . Org. Chem. 1996, 61, 8662-8663. (c)
Batanero, B.; Vago, M.; Barba, F. Heterocycles 2000, 53, 1337-1342.
(d) Batanero, B.; Barba, F. Electrochem. Commun. 2001, 3, 595-598.
(2) ] Setoguchi, N.; Takano, Y. Ch. Kitami. J pn. Kokai Tokkyo
Koho: J P 01006269A2, J an 1989.
(3) ] Howard, H. R. Eur. Pat. Appl. EP 409,435 (Cl. C07D403 14).
(4) ] Roberts, D. A.; Campbell, S. F. Faming Zhuanli Shenqing
Gongkai Shuomingshu CN 85,100,796 (Cl. C07D401/04), 1986.
(5) ] Theodoridis, G. US 4,909,829 (Cl.71-92; A01N43/64), Appl. 138,-
981, 1987.
(6) ] Faber, K.; Steininger, H.; Kappe, Th. J . Heterocycl. Chem. 1985,
22, 1081.
(20) ] Cathodic reduction of N-(2-acetylphenyl)-2,2,2-trichloroaceta-
mide yields N-(2-acetylphenyl)-2,2-dichloroacetamide as the only
product. This reaction involves protonation of the electrogenerated
anion. For this reason to protect the nitrogen atom, 2-aminophenone
(10 mmol) was refluxed in toluene for 3-6 h in the presence of the
corresponding alkyl iodide (20 mmol) to get N-alkyl-2-aminophenones
in very good yield. Subsequent acylation of them (10 mmol) with
commercially available trichloroacetic acid chloride (12 mmol) added
dropwise and refluxing in toluene afforded quantitatively N-(2-acyl-
(or aroyl)phenyl)-2,2,2-trichloro-N-alkylacetamides. These electroactive
acetamides have been used after purification in silica gel chromatog-
raphy with CHCl3/EtOH(100/1) as eluent.
(7) ] J i, R. Y. Med. Chem. Res. 1995, 5, 587.
(8) ] DeVita, R. J .; Hollings, D. D.; Goulet, M. T.; Wyvratt, M. J .;
Fisher, M. H.; Lo, J .-L.; Yang, Y. T.; Cheng, K.; Smith, R. G. Bioorg.
Med. Chem. Lett. 1999, 9, 2615.
(9) ] Rees, C. W.; Smithen, C. E. J . Chem. Soc. 1984, 938.
10.1021/jo0267403 CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/29/2003
3706
J . Org. Chem. 2003, 68, 3706-3709

SCHEME 1
electrolysis was slighly higher than expected for a 1e-
process. The reaction products were isolated and identi-
fied as 1-alkyl-3,3-dichloro-4-hydroxy-4-methyl-3,4-dihy-
dro-1H-quinolin-2-one (2) (as major product) and 1-alkyl-
3-chloro-4-methyl(or phenyl)-1H-quinolin-2-one (1) and
1-alkyl-4-hydroxy-4-methyl(or phenyl)-1,4-dihydroquino-
line-2,3-dione (3) as side products.
SCHEME 2
The formation of these compounds is explained as
follows: reduction of N-alkylacetamides at -0.8 V (vs
SCE), by uptake of 1e-, affords the corresponding radical
anion, which further decomposes to chlorine radical and
the anion a (Scheme 1).
As confirmed by our previous studies,1d the unusual
fragmentation of the radical anion is supported by
formation of anion a , which is highly stabilized by the
inductive effect of chlorine atoms and the resonance effect
of the adjacent carbonyl group. Subsequent intramolecu-
lar attack of the carbanion to the acyl (or aroyl) group
gives compound 2 as the major product.
As expected, 1-alkyl-4-hydroxy-4-methyl(or phenyl)-
1,4-dihydroquinoline-2,3-dione (3) is formed, due to the
basic medium of the catholyte, during workup (see the
Experimental Section), through a substitution of chlorine
by OH.
The selective reduction of N-(2-acetyl(or benzoyl)-
phenyl)-N-alkylacetamides to 2, without further reduc-
tion of 2 to 1-alkyl-3-chloro-4-methyl(or phenyl)-1H-
quinolin-2-one (1), is difficult due to the vicinity of the
two reduction peaks.
The product 1 arises from the electrochemical reduc-
tion of 2. It was confirmed when 2, previously isolated
and purified, was electrolized at -1.2 V. In this case, the
only obtained product was 1-alkyl-3-chloro-4-methyl(or
phenyl)-1H-quinolin-2-one (1), with an experimental
charge consumption corresponding to a 2e- process.
Controlled potential (-1.2 V vs SCE) reduction of N-(2-
benzoylphenyl)-2,2,2-trichloroacetamide affords 3-chloro-
1-methyl-4-phenyl-1H-quinolin-2-one (1d ) (70%) and
1-methyl-3-phenyl-1H-quinolin-2,4-dione (4d ) (21%). The
formation of 4d is summarized in Scheme 2.
Once 2d is formed, electrochemical C-Cl cleavage
takes place immediately in a 2e- process to give the
corresponding anion, which yields 1d by subsequent
elimination of OH- whereas 4d is formed by migration
of the phenyl group to the carbene center, generated after
elimination of Cl- (Scheme 2). The participation of the
phenyl group in this migration is clear because when
other groups are employed the rearrangement is only
negligible.
On the other hand, 2 can be converted quantitatively
into 3-hydroxy-3-alkyl(or aryl)-1-methyl-2(1H)-indolinone
(5) by alkali (5% NaOH water solution) in 30 min at room
temperature in the presence of air (Scheme 3). In the last
step, the air oxidation is a facile reaction of indole-2,3-
dihydrodiols, which has already been reported.21 The
process takes place through the formation of 3, which
leads to dioxindol 5 under the same alkaline conditions.
Exp er im en ta l Section
Gen er a l Electr och em ica l P r oced u r e. The electrochemical
reductions were performed under potentiostatic conditions in a
concentric cell with two compartments separated by a porous
(D3) glass diaphragm and equipped with a magnetic stirrer. A
mercury pool (20 cm2) was used as the cathode, a platinum plate
as the anode, and a saturated calomel electrode as the reference.
(21) ] Kafka, S.; Klasek, A.; Kosmrlj, J . J . Org. Chem. 2001, 66, 6394.
J . Org. Chem, Vol. 68, No. 9, 2003 3707

3.8 (s, 3H), 7.3 (t, 1H, J ) 7.1 Hz), 7.38 (d, 1H, J ) 8.3 Hz), 7.6
(t, 1H, J ) 7.1 Hz), 7.76 (d, 1H, J ) 8.3 Hz). 13C NMR (75.4
MHz, CDCl3) δ 16.6, 31, 114.7, 120.8, 122.8, 123.1, 125.6, 130.6,
139.8, 142.7, 158.2. MS m/e (rel intensity) EI 209 (M+ + 2, 33),
207 (M+, 100), 178 (32), 164 (16), 144 (45), 128 (23), 115 (27),
102 (15), 81 (19), 69 (36), 51 (14).
SCHEME 3
3-Ch lor o-1-eth yl-4-m eth yl-1H-qu in olin -2-on e (1b): 862
mg, 78% yield. Mp 110-112 °C. IR (KBr) ν 3087, 2978, 1643,
1597, 1093, 993, 821, 748 cm-1 1H NMR (300 MHz, CDCl3) δ
.
1.34 (t, 3H, J ) 7.1 Hz), 2.6 (s, 3H), 4.37 (q, 2H, J ) 7.1 Hz),
7.25 (t, 1H, J ) 7.5 Hz), 7.37 (d, 1H, J ) 8.4 Hz), 7.55 (t, 1H, J
) 7.1 Hz), 7.72 (dd, 1H, J 1 ) 8.1 Hz, J 2 ) 1.3 Hz). 13C NMR
(75.4 MHz, CDCl3) δ 12.5, 16.4, 38.5, 114.2, 120.7, 122.3, 125.5,
126.1, 130.3, 136.7, 142.3, 157.3. MS m/e (rel intensity) EI 223
(M+ + 2, 23), 221 (M+, 69), 220 (M+ - 1, 68), 195 (34), 193 (100),
164 (23), 143 (19), 130 (38), 128 (29), 115 (19), 101 (16), 89 (8),
77 (20), 63 (13), 51 (14). Anal. Calcd for C12ClH12NO: C, 65.01;
H, 5.42; N, 6.32. Found: C, 64.77; H, 5.62; N, 6.29.
3-Ch lor o-1-isopr opyl-4-m eth yl-1H-qu in olin -2-on e (1c): 963
mg, 82% yield. Mp 64-66 °C. IR (KBr) ν 2970, 2933, 1652, 1600,
1380, 1365, 1302, 1025, 749 cm-1. 1H NMR (300 MHz, CDCl3) δ
1.34 (d, 6H, J ) 7.0 Hz), 2.62 (s, 3H), 5.42 (br s, 1H), 7.22-7.3
(t, 1H, J ) 7.6 Hz), 7.5-7.6 (m, 2H), 7.74 (d, 1H, J ) 8.3 Hz).
13C NMR (75.4 MHz, CDCl3) δ 16.7, 19.9, 48.8, 115.2, 121.5,
122.4, 125.9, 127.1, 129.9, 137.4, 142.2, 158.2. MS m/e (rel
intensity) EI 237 (M+ + 2, 8), 235 (M+, 25), 234 (M+ - 1, 13),
195 (34), 193 (100), 176 (4), 164 (15), 130 (22), 128 (15), 103 (7),
77 (8). Anal. Calcd for C13ClH14NO: C, 66.24; H, 5.94; N, 5.94.
Found: C, 65.97; H, 5.77; N, 6.11.
The solvent-supporting electrolyte system (SSE) was nominally
anhydrous acetonitrile containing 0.05 M lithium perchlorate.
Anhydrous potassium carbonate was added to the anodic
compartment for “in situ” neutralization of the generated
perchloric acid.
A solution of the electroactive N-(2-acyl(or aroyl)phenyl)-2,2,2-
trichloro-N-alkylacetamide (5.0 mmol in 30 mL of SSE) was
electrolyzed at a constant potential of -0.8 V and -1.2 V (versus
SCE). The initial current was 200 or 300 mA, respectively,
depending on the applied potential. When the current fell almost
to zero, the reduction was finished and the solvent in the
cathodic solution was removed under reduced pressure. The
residue was extracted with ether/water and the organic phase
dried over Na2SO4 and concentrated by evaporation. The result-
ing solid or oil was chromatographed on a silica gel (18 × 3 cm)
column, using toluene/MeOH (80/1) as eluent. Spectroscopical
description of all the compounds is given below.
3-Ch lor o-1-m eth yl-4-p h en yl-1H-qu in olin -2-on e (1d ): 942
mg, 70% yield. Mp 163-165 °C. IR (KBr) ν 2925, 1650, 1597,
1
1080, 754, 701 cm-1. H NMR (300 MHz, CDCl3) δ 3.85 (s, 3H),
7.1-7.2 (m, 2H), 7.27 (d, 2H, J ) 7.3 Hz), 7.38-7.42 (d, 1H, J )
7.7 Hz), 7.45-7.6 (m, 4H). 13C NMR (75.4 MHz, CDCl3) δ 31.2,
114.5, 121.2, 122.7, 128.3, 128.8, 129, 130.8, 135.4, 138.6, 147.4,
158.6. MS m/e (rel intensity) EI 271 (M+ + 2, 34), 269 (M+, 100),
243 (11), 241 (31), 234 (18), 204 (14), 190 (16), 176 (9), 165 (13),
N -(2-Ac e t y lp h e n y l)-2,2,2,-t r ic h lo r o -N -m e t h y la c e t a -
m id e: Mp 58 °C. IR (KBr) ν 3069, 2973, 1730, 1685, 1601, 1364,
1
1250, 839, 763, 661 cm-1. H NMR (300 MHz, CDCl3) δ 2.57 (s,
152 (4), 117 (6), 102 (6), 63 (5), 51 (8). Anal. Calcd for C16ClH12
-
3H), 3.68 (br s, 3H), 7.2-7.3 (m, 1H), 7.4-7.62 (m, 2H), 7.7-7.8
(m, 1H). 13C NMR (75.4 MHz, CDCl3) δ 28.4, 41.8, 92.6, 127.6,
128, 129, 132.6, 135.5, 141.7, 159.5, 198.6. MS m/e (rel intensity)
EI 293 (M+, 1), 250 (32), 215 (10), 182 (61), 176 (100), 148 (68),
134 (72), 104 (28), 91 (36), 77 (69), 51 (32).
NO: C, 71.24; H, 4.45; N, 5.19. Found: C, 71.22; H, 4.67; N,
5.04.
Electr och em ica l Red u ction a t -0.8 V (vs SCE). 3,3-
Dich lor o-4-h yd r oxy-1,4-d im eth yl-3,4-d ih yd r o-1H-qu in olin -
2-on e (2a ): 660 mg, 51% yield. Mp 158-160 °C. IR (KBr) ν 3411,
2988, 1671, 1600, 1370, 1183, 768 cm-1 1H NMR (300 MHz,
.
N-(2-Acetylph en yl)-2,2,2,-tr ich lor o-N-eth ylacetam ide: Mp
65-67 °C. IR (NaCl) ν 3071, 2979, 1736, 1683, 1596, 1250, 841,
CDCl3) δ 1.55 (br s, 3H), 2.8 (br s, 1H), 3.5 (s, 3H), 7.07 (d, 1H,
J ) 8.1 Hz), 7.22 (t, 1H, J ) 7.6 Hz), 7.39 (t, 1H, J ) 8.1 Hz),
7.7 (br s, 1H). 13C NMR (75.4 MHz, CDCl3) δ 24.3, 29.3, 31.2,
76.9, 114.8, 124.4, 128.1, 129.0, 130.0, 135.6, 161.5. MS m/e (rel
intensity) EI 261 (M+ + 2, 10), 259 (M+, 16), 218 (9), 216 (14),
182 (5), 180 (12), 149 (100), 134 (59), 117 (5), 91 (6), 77 (15), 51
(5). Anal. Calcd for C11Cl2H11NO2: C, 50.77; H, 4.23; N, 5.38.
Found: C, 51.02; H, 4.20; N, 5.23.
3,3-Dich lor o-1-et h yl-4-h yd r oxy-4-m et h yl-3,4-d ih yd r o-
1H-qu in olin -2-on e (2b): 737 mg, 54% yield. Mp 98-100 °C.
IR (KBr) ν 3436, 2981, 1682, 1604, 1385, 954, 842, 757 cm-1. 1H
NMR (300 MHz, CDCl3) δ 1.28 (t, 3H, J ) 7.2 Hz), 1.51 (br s,
3H), 3.0 (br s, 1H), 4.1 (br s, 2H), 7.1 (d, 1H, J ) 8.2 Hz), 7.2 (t,
1H, J ) 7.6 Hz), 7.36 (t, 1H, J ) 7.6 Hz), 7.67 (br s, 1H). 13C
NMR (75.4 MHz, CDCl3) δ 12.3, 24.9, 30.0, 39.6, 77.4, 115.2,
124.9, 125.2, 129.5, 132, 134.8, 161.6. MS m/e (rel intensity) EI
275 (M+ + 2, 24), 273 (M+, 36), 232 (18), 230 (19), 194 (21), 163
1
765, 669 cm-1. H NMR (300 MHz, CDCl3) δ 1.17 (br s, 3H), 2.6
(s, 3H), 4.31 (br s, 2H), 7.2-7.9 (m, 4H). 13C NMR (75.4 MHz,
CDCl3) δ 12.6, 28.6, 47.5, 92.7, 128.3, 129.2, 129.5, 130.0, 132.4,
135.7, 162.7, 200.2. MS m/e (rel intensity) EI 274 (M+ + 2 - Cl,
4), 272 (M+ - Cl, 6), 268 (3), 266 (9), 230 (4), 190 (27), 162 (100),
146 (29), 144 (66), 116 (26), 105 (9), 91 (13), 77 (20), 51 (6).
N-(2-Acet ylp h en yl)-2,2,2,-t r ich lor o-N-isop r op yla cet a -
m id e: Mp 69-71 °C. IR (KBr) ν 3071, 2977, 1735, 1689, 1596,
1247, 836, 758, 667 cm-1. 1H NMR (300 MHz, CDCl3) δ 0.91 (br
s, 3H), 1.24 (d, 3H, J ) 6.4 Hz), 2.51 (s, 3H), 5.08 (br s, 1H),
7.1-7.4 (m, 1H), 7.4-7.57 (m, 2H), 7.77 (br s, 1H). 13C NMR
(75.4 MHz, CDCl3) δ 19.1, 20.9, 28.4, 53.4, 94, 128.8, 129.5, 130.1,
131.7, 132.3, 132.9, 160, 198.2. MS m/e (rel intensity) EI 288
(M+ + 2 - Cl, 16), 286 (M+ - Cl, 25), 238 (5), 236 (5), 204 (8),
176 (48), 162 (100), 144 (71), 116 (31), 91 (21), 77 (15), 63 (7), 51
(6).
N -(2-Be n zoylp h e n yl)-2,2,2,-t r ich lor o-N -m e t h yla ce t a -
m id e: Mp 67 °C. IR (NaCl) ν 3064, 1663, 1598, 1377, 1275, 840,
(100), 148 (85), 130 (28), 105 (4), 77 (19). Anal. Calcd for C12-
Cl2H13NO2: C, 52.55; H, 4.74; N, 5.11. Found: C, 52.42; H, 4.94;
N, 4.99.
750 cm-1 1H NMR (300 MHz, CDCl3) δ 3.63 (s, 3H), 7.3-7.6
.
(m, 7H), 7.75-7.85 (m, 2H). 13C NMR (75.4 MHz, CDCl3) δ 42.6,
93.1, 128.0, 128.4, 128.6, 130.7, 130.9, 132.3, 133.6, 136.8, 137.0,
142.8, 160.1, 195.5. MS m/e (rel intensity) EI 357 (M+ + 2, 0.3),
355 (M+, 0.2), 322 (M+ + 2 - Cl, 2), 320 (M+ - Cl, 3), 284 (3),
252 (8), 250 (9), 238 (22), 210 (1), 180 (15), 152 (10), 132 (8), 105
(100), 91 (17), 77 (68), 51 (18).
3,3-Dich lor o-4-h ydr oxy-1-isopr opyl-4-m eth yl-3,4-dih ydr o-
1H-qu in olin -2-on e (2c): 832 mg, 58% yield. Mp 133-134 °C.
IR (KBr) ν 3470, 2970, 2934, 1685, 1601, 1365, 1342, 837, 758
cm-1 1H NMR (300 MHz, CDCl3) δ 1.5-1.61 (m, 9H), 2.75 (br
.
s, 1H), 4.6 (sept, 1H, J ) 6.8 Hz), 7.15 (d, 1H, J ) 8.2 Hz), 7.21
(d, 1H, J ) 7.5 Hz), 7.35 (t, 1H, J ) 8.2 Hz), 7.65 (br s, 1H). 13C
NMR (75.4 MHz, CDCl3) δ 19.0, 20.3, 24.2, 29.4, 51.7, 77.4, 116.6,
124.9, 125.9, 129.2, 132.3, 136.2, 161.3. MS m/e (rel intensity)
EI 289 (M+ + 2, 12), 287 (M+, 18), 254 (5), 252 (12), 244 (11),
210 (5), 194 (8), 177 (22), 162 (48), 135 (100), 120 (39), 102 (9),
Electr och em ical Redu ction at -1.2 V (vs SCE). 3-Ch lor o-
1,4-d im eth yl-1H-qu in olin -2-on e (1a ): 797 mg, 77% yield. Mp
180 °C [lit.9 mp 187 °C]. IR (KBr) ν 2924, 1648, 1596, 1081, 963,
814, 749 cm-1 1H NMR [10] (300 MHz, CDCl3) δ 2.65 (s, 3H),
.
3708 J . Org. Chem., Vol. 68, No. 9, 2003

83 (15), 77 (16), 51 (8). Anal. Calcd for C13Cl2H15NO2: C, 54.17;
H, 5.21; N, 4.86. Found: C, 54.07; H, 4.93; N, 5.01.
(300 MHz, CDCl3) δ 3.57 (s, 3H), 4.4 (s, 1H), 7.1-7.4 (m, 7H),
7.6 (t, 1H, J ) 7.8 Hz), 7.9 (d, 1H, J ) 7.8 Hz). 13C NMR (75.4
MHz, CDCl3) δ 30.6, 115.3, 121.3, 124.2, 125.9, 128.6, 129.2,
129.5, 136.5, 138.1, 142.6, 171.3, 192.8. MS m/e (rel intensity)
EI 267 (M+, 16), 251 (15), 250 (20), 210 (8), 162 (60), 134 (8),
105 (100), 77 (61), 63 (7), 51 (19). Anal. Calcd for C16H13NO3:
C, 71.91; H, 4.87; N, 5.24. Found: C, 72.10; H, 4.60; N, 5.42.
4-Hydr oxy-1-m eth yl-3-ph en yl-1H-qu in olin -2-on e (4d): 262
mg, 21% yield. Mp 222-224 °C [lit.22 mp 225 °C]. IR (KBr) ν
4-H yd r oxy-1,4-d im e t h yl-1,4-d ih yd r oq u in olin e -2,3-d i-
on e (3a ): 205 mg, 20% yield. Mp 147-149 °C. IR (KBr) ν 3384,
2928, 1711, 1676, 1603, 1372, 1100, 758 cm-1 1H NMR (300
.
MHz, CDCl3) δ 1.62 (s, 3H), 3.5 (s, 3H), 7.1-7.2 (m, 2H), 7.67
(td, 1H, J 1 ) 1.6 Hz, J 2 ) 7.7 Hz), 8.0 (dd, 1H, J 1 ) 1.6 Hz, J 2
) 7.7 Hz). 13C NMR (75.4 MHz, CDCl3) δ 28.5, 29.3, 30, 114.7,
123.4, 125.2, 127.9, 135.9, 142.2, 172.5, 194.6. MS m/e (rel
intensity) EI 206 (M+ + 1, 4), 205 (M+, 26), 163 (29), 162 (100),
149 (25), 134 (45), 116 (9), 106 (13), 91 (11), 77 (29), 63 (8), 51
(11). Anal. Calcd for C11H11NO3: C, 64.39; H, 5.37; N, 6.83.
Found: C, 64.25; H, 5.48; N, 6.73.
3261, 2924, 1623, 1393, 1271, 752 cm-1 1H NMR (300 MHz,
.
CDCl3) δ 3.9 (s, 3H), 7.14 (br s, 1H), 7.19 (t, 1H, J ) 7.3 Hz),
7.35-7.6 (m, 8H). 13C NMR (75.4 MHz, CDCl3) δ 31.1, 114.4,
122.3, 123.3, 123.5, 126.4, 127.5, 128.4, 128.8, 130.1, 133.1, 134.6,
140.9, 159.1. MS m/e (rel intensity) EI 251 (M+ + 1, 90), 250
(M+, 100), 235 (5), 223 (4), 179 (5), 165 (14), 152 (11), 77 (9), 63
(7).
1-Eth yl-4-h yd r oxy-4-m eth yl-1,4-d ih yd r oqu in olin e-2,3-d i-
on e (3b): 230 mg, 21% yield. Mp 142-143 °C. IR (KBr) ν 3400,
2989, 1712, 1677, 1601, 1382, 1198, 1108, 759 cm-1 1H NMR
.
(300 MHz, CDCl3) δ 1.25 (t, 3H, J ) 7.1 Hz), 1.57 (s, 3H), 3.97
(br s, 1H), 4.08 (m, 2H), 7.12-7.2 (m, 2H), 7.63 (td, 1H, J 1 ) 1.8
Hz, J 2 ) 7.9 Hz), 7.95 (dd, 1H, J 1 ) 1.6 Hz, J 2 ) 7.7 Hz). 13C
NMR (75.4 MHz, CDCl3) δ 12.5, 28.9, 38.2, 79.5, 115.2, 120.6,
123.8, 128.7, 136.5, 141.5, 172.8, 195.4. MS m/e (rel intensity)
EI 219 (M+, 26), 177 (48), 176 (100), 162 (10), 148 (68), 130 (18),
3-H yd r oxy-1,3-d im e t h yl-1,3-d ih yd r o-2H -in d ol-2-on e
(5a ): mp 139-140 °C [lit.23 mp 140-142 °C]. Spectroscopic data
(IR, NMR, and MS) are coincident with those described in the
literature.23
3-H yd r oxy-1-m et h yl-3-p h en yl-1,3-d ih yd r o-2H -in d ol-2-
on e (5d ): mp 141 °C [lit.21 mp 141-143 °C]. MS m/e (rel
intensity) EI 240 (M+ + 1, 13), 239 (M+, 72), 211 (63), 210 (100),
195 (18), 194 (69), 181 (7), 165 (13), 152 (15), 134 (24), 105 (32),
91 (15), 77 (96), 63 (16), 51 (45). Spectroscopic data (IR and NMR)
are coincident with those described in the literature.21
120 (11), 104 (7), 77 (18), 65 (6), 51 (5). Anal. Calcd for C12H13
-
NO3: C, 65.75; H, 5.94; N, 6.39. Found: C, 65.65; H, 5.97; N,
6.5.
4-Hyd r oxy-1-isop r op yl-4-m eth yl-1,4-d ih yd r oqu in olin e-
2,3-d ion e (3c): 245 mg, 21% yield; oil. IR (KBr) ν 3430, 2974,
2932, 1721, 1655, 1598, 1370, 1340, 1195, 1109, 754 cm-1 1H
.
Ack n ow led gm en t. This study was financed by the
spanish Ministry of Science and Technology (BQU2001-
1083). B. Batanero thanks to this Ministry for the
“Ramon y Cajal” financiation.
NMR (300 MHz, CDCl3) δ 1.54 (s, 3H), 1.58 (s, 6H), 3.94 (br s,
1H), 4.92 (h, 1H, J ) 6.9 Hz), 7.12-7.24 (m, 2H), 7.62 (t, 1H, J
) 7.7 Hz), 7.96 (d, 1H, J ) 7.7 Hz). 13C NMR (75.4 MHz, CDCl3)
δ 19.0, 20.3, 28.4, 43.7, 48.5, 115.7, 121.8, 123.4, 128.4, 130.5,
135.6, 172.9, 195.2. MS m/e (rel intensity) EI 234 (M+ + 1, 3),
233 (M+, 21), 191 (45), 190 (57), 149 (42), 148 (100), 130 (8), 120
(9), 104 (4), 92 (10), 77 (14), 65 (7). Anal. Calcd for C13H15NO3:
C, 66.95; H, 6.44; N, 6.01. Found: C, 67.16; H, 6.41; N, 6.14.
4-Hyd r oxy-1-m eth yl-4-p h en yl-1,4-d ih yd r oqu in olin e-2,3-
d ion e (3d ): 227 mg, 17% yield. Mp 161-162 °C. IR (KBr) ν
J O0267403
(22) ] Stadlbauer, W.; Schmut, O.; Kappe, Th. Monatsh. Chem. 1980,
111, 1005.
(23) ] Alvarez, R. G.; Hunter, I. S.; Suckling, C. J .; Thomas, M.;
Vitinius, U. Tetrahedron 2001, 57, 8581.
3423, 3071, 1708, 1667, 1602, 1361, 1098, 757 cm-1 1H NMR
.
J . Org. Chem, Vol. 68, No. 9, 2003 3709