(Bromodimethyl)sulfonium bromide catalyzed solvent-free friedlander synthesis of substituted quinolines

Article abstract of DOI:10.1002/jhet.873

A simple and efficient (bromodimethyl)sulfonium bromide catalyzed synthesis of quinolines, by condensation of α-amino carbonyl, that is, 2-aminobenzophenone and 2-aminoacetophenone with α-methylene containing carbonyl like 1,3-dicarbonyls has been develop

Full text of DOI:10.1002/jhet.873

July 2012
(Bromodimethyl)sulfonium Bromide Catalyzed Solvent-Free
Friedlander Synthesis of Substituted Quinolines
833
*
R. Venkatesham, A. Manjula, and B. Vittal Rao
Organic Chemistry Division-II, Indian Institute of Chemical Technology,
Hyderabad 500 607, India
*
E-mail: vittalrao@iict.res.in or raobommena@gmail.com
Received December 15, 2010
DOI 10.1002/jhet.873
View this article online at wileyonlinelibrary.com.
A simple and efficient (bromodimethyl)sulfonium bromide catalyzed synthesis of quinolines, by
condensation of a-amino carbonyl, that is, 2-aminobenzophenone and 2-aminoacetophenone with
a-methylene containing carbonyl like 1,3-dicarbonyls has been developed. The reaction is versatile,
solvent-free protocol for generation of structurally diverse quinolines.
J. Heterocyclic Chem., 49, 833 (2012).
INTRODUCTION
carbonyl with carbonyl compound containing a reactive
a-methylene group. Recently, heterogenous catalysis has
also been employed in Friedlander synthesis [14]. Many
of the available methods suffer from several drawbacks
like harsh reaction conditions, side reactions or multiple
products, and tedious work-up or purification techniques,
involving solvents and toxic reagents.
Qunine identified in 1820 as an active ingredient in
Cinchona bark for treatment of malaria is perhaps the
first isolated molecule from natural sources to be used
as a drug. Similarly, pamaquine [1], again an antimalarial
drug, is the first known synthetic drug ever used in
humans. Both of them possess quinoline skeleton.
Nearly all of the known antimalarial drugs belong to this
class [1,2]. Quinolines form major components of a
variety of natural products. They are also versatile
building blocks of various pharma active molecules. Of
late, a number of antituberculosis drugs have evolved
based on aryl quinolines like TMC-207 [3] (Fig. 1),
exhibiting high potency and novel mode of action, which
is in phase-II clinical trials for multidrug-resistant
tuberculosis. Quinolines have also been shown to exhibit
antiasthmatic [4], antidiabetic [5], in vitro antifungal [6],
antiviral [7], anti-inflammatory [8], and antiproliferative
activities [9]. Further more, as a consequence of their
inherent fluorescent nature, they are of great interest as
light emitting chromophores [10]. Applications of
quinolines as the ligands for transition metals in chiral
catalysis are also plentiful [11].
RESULTS AND DISCUSSION
In continuation of our ongoing projects in developing
novel solvent-free and environmentally benign synthetic
methods for pharmaceutically and agrochemically im-
portant heterocycles, we herein report (bromodimethyl)-
sulfonium bromide (BDMS) catalyzed Friedlander
synthesis of quinoline in solvent-free conditions. BDMS
has been proven to be a versatile catalyst for various
transformations, which has been frequently employed in
our laboratory [15], such as in construction of b-amino
ketones and imidazo[1,2-a] pyridines, thia-Michael
addition etc.
At the outset, the amino carbonyl, 2-amino benzophe-
none was reacted with ethylacetoacetate in the presence
of BDMS at 50ꢀC in solvent-free conditions (Scheme 1).
The product, 3-methyl-4-phenylquinoline-3-carboxylic
acid ethyl ester, was obtained by simply filtering the pre-
cipitated product from reaction mixture. Then, efforts
were focused on the optimization of catalyst concentra-
tion. The reaction does not progress in the absence of
catalyst. It was found to be sluggish as well as low yielding
with 5 mol % BDMS (Table 1). Catalyst (10 mol %) was
Owing to the wide range of applications, quinoline
synthesis has received much attention, and many classi-
cal methods for synthesis, such as Skraup, Doebner–
Vonmiller, Conrad–Limbach, Combes, Pfitzinger, and
Friedlander, are in vogue. Friedlander synthesis of
quinoline has proven to be the most versatile, straightfor-
ward, and powerful method. It is a Bronsted acid [12]
or Lewis acid [13] catalyzed condensation of a-amino
© 2012 HeteroCorporation

834
R. Venkatesham, A. Manjula, and B. Vittal Rao
Vol 49
Figure 1. Quinolines with applications in pharmaceutical and synthetic chemistry.
ideal for the quinoline synthesis. Further increase in cata-
lyst concentration does not improve reaction yield or
time. The generality of method was investigated by
employing 1,3-diketones, cyclic ketones, ketones, alde-
hydes, and so forth, and results are presented in Table 2.
In all cases, reactions are facile and pure products were
obtained without involving any additional purification.
This method is general and tolerant to substitutions on
the amino benzophenone as well as changes in the car-
bonyls (entries 1–20, Table 2). Heterocyclic aldehydes/
ketones gave lower yields, and reactions were time con-
suming. Aliphatic and aromatic aldehydes were not good
substrates and reactions did not progress. The yields were
also poor with aliphatic carbonyls. The same was the
case when carbonyls with electron donating substitutions
were employed. The reaction does not proceed with
triflouro ethylacetoacetate.
Encouraged by the results 2-amino benzophenone was
replaced by 2-amino acetophenone to effect of R1 on
the reaction protocol. Condensation of 2-amino aceto-
phenone with ethylacetoacetate and 10 mol % BDMS
was sluggish and low yielding. However, when the
catalyst concentration was enhanced to 40 mol %, the
reaction was effective yielding corresponding quinoline
in 81% in 20 min. The reaction was extendable with
2-amino benzophenone and other diketones without any
hassles (entries 19–21, Table 2).
reaction and water elimination also leads to the same
product. In this case, the aldol formation seems to be
the first step, because the reaction does not proceed at
low temperatures and stops at simple Schiff’s base
formation. Aldol condensation, being an equilibration
reaction, can be propelled only by heating. BDMS has a
role in both enolization of the carbonyl compound with
a-methylene group as well as the final Schiff’s base
formation and cyclization. The plausible mechanism is
given in Figure 2.
CONCLUSIONS
To the best of our knowledge, this is the first report
of BDMS catalyzed Friedlander synthesis of quinoline
starting from 2-amino carbonyls, that is, 2-aminobenzo-
phenone and 2-aminoacetophenone. The reaction is a
versatile, solvent-free protocol for generation of structur-
ally diverse quinolines. Several advantages offered by
this protocol include operational simplicity, inexpensive
reagents, short reaction times, and hassle-free work-up
and purification.
EXPERIMENTAL
General procedure for the preparation of substituted quino-
lines: a mixture of 2-amino aryl ketone (1 mmol), enolizable
ketone (1 mmol), and (bromodimethyl)sulfonium bromide
(BDMS) 10 mol % was stirred at 50ꢀC under solvent-free con-
dition till the completion of the reaction as indicated by TLC
(Table 2). After completion of the reaction, the reaction
mixture was triturated with 2–3 mL of ethyl acetate and
The Friedlander synthesis mechanism goes via an
imine formation and an aldol condensation, either of
which can be the first step. A rate limiting aldol
reaction, followed by elimination of water and imine
formation with further loss of water leads to quinolines.
Alternately, Schiff’s base formation followed by aldol
Table 1
Optimization of BDMS concentration for quinoline synthesis (2-amino
benzophenone and ethylacetoacetate).
Scheme 1. BDMS catalyzed synthesis of quinolines.
S. No.
BDMS
Yield (%)
Time
1
2
3
4
0
5
10
20
Traces
50
80
>24 h
2 h
50 min
50 min
80
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July 2012
(Bromodimethyl)sulfonium Bromide Catalyzed Solvent-Free Friedlander
Synthesis of Substituted Quinolines
835
Table 2
BDMS catalyzed synthesis of substituted quinolines.
Entry
1
2-Amino carbonyl
a-Methylene carbonyl
Product
Yield (isolated, %)
80
Time
50 min
2
81
84
81
80
92
85
81
72
93
45 min
35 min
55 min
55 min
30 min
50 min
50 min
75 min
20 min
3
4
5
6
7
8
9
10
11
81
20 min
(Continued)
Journal of Heterocyclic Chemistry
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R. Venkatesham, A. Manjula, and B. Vittal Rao
Vol 49
Table 2
(Continued)
EntrEyntry
12
2-Amino carbonyl
a-Methylene carbonyl
Product
Yield (isolated, %)
88
Time
10 min
13
64
12 h
14
15
80
40
50 min
12 h
16
17
32
41
10 h
10 h
18
19
20
21
60
81
62
83
12 h
20 min
5 h
20 min
22
23
No reaction
No reaction
–
–
–
–
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2012
(Bromodimethyl)sulfonium Bromide Catalyzed Solvent-Free Friedlander
Synthesis of Substituted Quinolines
837
13C NMR (75 MHz, DMSO-d6): 156.67, 154.81, 138.29,
135.08, 133.77, 132.73, 130.74, 129.55, 129.23, 129.17,
129.09, 128.77, 128.63, 127.02, 126,50, 122.44, 18.04; MS
(ESI): m/z = 296 [M+H]+; HRMS (ESI) Calculated for C22H18N
[M+H]+ 296.1433 found 296.1451; I.R. (KBr, cmÀ1) : 3458,
3049, 2833, 2511, 1626, 759, 704.
16-Phenyl-6,7,8,9,10,11,12,13,14,15-decahydro-5-azacyclodo-
deca[b]naphtha lene(C25H29N Table 1, entry 9). White solid
(M.p. 217–220ꢀC); 1H NMR (300 MHz, DMSO-d6): d 8.76
(d, 1H, J = 8.1 Hz), 8.00 (t, 1H, J = 7.9 Hz), 7.71–7.59 (m, 4H),
7.43 (d, 1H, J = 8.3 Hz), 7.32–7.27 (q, 2H), 3.49 (t, 2H, J = 7.5
Hz), 2.76 (t, 2H, J = 7.7 Hz), 2.20–2.10 (m, 2H), 1.97–1.25 (m,
14H); 13C NMR (75 MHz, DMSO-d6): 160.25, 156.62, 136.37,
134.48, 134.26, 133.38, 129.30, 128.81, 128.53, 128.29, 128.14,
126.95, 126.73, 120.00, 29.92, 28.24, 27.66, 27.49, 27.29, 26.75,
26.59, 22.20, 21.77; MS (ESI): m/z = 344 [M+H]+; HRMS (ESI)
Calculated for C22H18N [M+H]+ 344.2378 found 344.2366; I.R.
(KBr, cmÀ1): 3412, 3054, 2926, 2850, 2483, 1930.
2-Chloro-11-phenyl-6H-indeno[2,1-b]quinoline (C22H14NCl,
Table 1, entry 3). Pale yellow solid (M.p. 178–180ꢀC); 1H
NMR (300 MHz, DMSO-d6): d 8.54 (d, 1H, J = 4.1 Hz), 8.43
(d, 1H, J = 8.9 Hz), 7.70 (dd, 1H, J = 9.1 Hz), 7.66–7.59 (m,
4H), 7.56–7.46 (m, 5H), 3.94 (s, 2H); 13C NMR (75 MHz,
DMSO-d6): 183.77, 181.68, 175.19, 172.05, 169.02, 168.62,
167.80, 166.76, 166.70, 166.64, 166.58, 165.36, 163.61,
161.81, 159.81, 71.39; MS (ESI): m/z = 328 [M+H]+; HRMS
(ESI) Calculated for C22H14NCl[M+H]+ 328.0893 found
328.0887; I.R. (KBr, cmÀ1): 3448, 3056, 2902, 2454, 1339.
6-Chloro-2-methyl-4-phenyl-quinoline-3-carboxylic acid
ethylester (C19H16NO2Cl, Table 1, entry 4, ref. 13d). White
Figure 2. Plausible mechanism of BDMS catalyzed quinoline synthesis.
precipitated solid filtered. The product so obtained was pure
enough for all practical purposes. Compounds were character-
ized by spectral data given below.
Spectral data. 10-Phenyl-11H-indeno[1,2-b]quinoline (C22H15N,
1
Table 1, entry 10). Pale yellow solid (M.p. 144–148ꢀC); H NMR
(300 MHz, DMSO-d6): d 8.47 (t, 2H, J = 4.9 Hz), 8.35 (t, 1H, J =
7.8 Hz), 7.74 (d, 1H, J = 8.8 Hz), 7.63–7.48 (m, 9H), 3.96 (s, 2H);
13C NMR (75 MHz, DMSO-d6): 146.23, 145.47, 144.86, 137.69,
135.00, 133.58, 131.32, 130.18, 129.27, 128.90, 127.81, 126.65,
126.06, 125.78, 128.65, 122.35, 33.86; MS (ESI): m/z = 294
[M+H]+; HRMS (ESI) Calculated for C22H16N [M+H]+ 294.1282
found 294.1291; I.R. (KBr, cmÀ1) : 3384, 3036, 2608, 1524, 763.
4-Phenyl-2-pyridine-3-yl-quinoline (C20H14N2, Table 1, entry
1
solid (M.p. 105–107ꢀC); H NMR (300 MHz, CDCl3): d 7.99
(d, 1H, J = 9.1 Hz), 7.63 (dd, 1H, J = 9.1 Hz), 7.51–746
(m, 4H), 7.35–7.31 (m, 2H), 4.06–3.98 (q, 2H), 2.74 (s, 3H),
0.93 (t, 3H, J = 6.8 Hz); MS (ESI): m/z = 325 [M+H]+; I.R.
(KBr, cmÀ1): 3423, 2927, 1719, 1220, 1070.
1–(6-Chloro-2-methyl-4-phenyl-quinoline-3-yl)-ethanone
(C18H14NOCl, Table 1, entry 5, ref. 13d). White solid (M.p.
153–156ꢀC); 1H NMR (300 MHz, DMSO-d6): d 8.03 (d, 1H,
J = 8.9 Hz), 7.67 (d, 1H, J = 8.9 Hz), 7.56 (t, 3H, J = 3.9 Hz),
7.51 (d, 1H, J = 2.1 Hz), 3.75 (m, 2H), 2.65 (s, 3H), 1.97 (s,
3H); MS (ESI): m/z = 296 [M+H]+; I.R. (KBr, cmÀ1): 3420,
2925, 1700.
1
13). Pale brown solid (M.p. 116–118ꢀC); H NMR (300 MHz,
DMSO-d6): d 9.63 (d, 1H, J = 10.8 Hz), 9.08 (d, 1H, J = 8.1
Hz), 8.91 (d, 1H, J = 5.1 Hz), 8.20 (d, 1H, J = 8.3 Hz),
8.13–8.07 (m, 1H), 7.97–7.76 (m, 3H), 7.62–7.52 (m, 6H); 13C
NMR (75 MHz, DMSO-d6): 151.82, 149.41, 147.91, 146.25,
144.70, 139.47, 137.06, 135.61, 133.42, 132.04, 130.48,
129.74, 129.65, 128.99, 127.78, 125.67, 125.39, 119.00; MS
2-Methyl-4-phenyl-quinoline-3-carboxylic acid methyl ester
(C18H151NO2, Table 1, entry 7, 13b). White solid (M.p. 94–
95ꢀC); H NMR (300 MHz, DMSO-d6): d 8.58 (m, 1H), 8.03
(t, 1H, J = 6.8 Hz), 7.77–7.71 (m, 2H). 7.61–7.54 (m, 3H),
7.40–7.33 (m, 2H), 3.60 (s, 3H), 3.0 (s, 3H); MS (ESI): m/z =
278 [M+H]+; I.R. (KBr, cmÀ1): 3447, 2942, 2494, 1735, 1230.
1-(2-Methyl-4-phenyl-quinoline-3-yl)-ethanone (C18H15NO,
(ESI): m/z
=
283 [M+H]+; HRMS (ESI) Calculated for
C20H15N2 [M+H]+ 283.1235 found 283.1234; I.R. (KBr, cmÀ1
: 3440, 3060, 2047, 1587, 1482, 766, 699.
)
2-Chloro-10-phenyl-11H-indeno[1,2-b]quinoline (C22H14
NCl, Table 1, entry 11). Pale yellow solid (M.p. 315–318ꢀC);1H
NMR (300 MHz, DMSO-d6): d 8.88 (d, 1H, J = 8.8 Hz), 8.69
(d, 1H, J = 7.8 Hz), 7.99 (t, 1H, J = 7.8 Hz), 7.92 (s, 1H),
7.86 (t, 1H, J = 7.8 Hz), 7.74–7.62 (m, 4H), 7.58 (t, 2H, J =
7.8 Hz), 7.52 (t, 1H, J = 8.8 Hz), 4.10 (s, 2H); 13C NMR (75
MHz, DMSO-d6): 149.11, 141.28, 137.34, 135.64, 132.58,
134.30, 138.11, 131.87, 129.50, 129.24, 129.05, 128.54,
128.04, 126.33, 125.75, 124.98, 123.75, 123.45, 34.25; MS
1
Table 1, entry 2, ref. 13d). White solid (M.p. 114–116ꢀC); H
NMR (300 MHz, DMSO-d6): d 7.99 (d, 1H, J = 8.3 Hz), 7.70
(t, 1H, J = 8.1 Hz), 7.58 (d, 1H, J = 8.3 Hz), 7.55–7.50 (m,3H),
7.44 (t, 1H, J = 7.2 Hz), 7.36–7.31 (m, 2H), 2.63 (s, 3H), 1.97
(s, 3H); MS (ESI): m/z = 262 [M+H]+; I.R. (KBr, cmÀ1): 3424,
2922, 1688.
9-Phenyl-2,3-dihydro-1H-cylopenta[b]quinoline (C18H15N,
Table 1, entry 6, ref. 13a). Lite dark solid (M.p. 130–132ꢀC); 1H
NMR (300 MHz, DMSO-d6): d 8.69–8.61 (q, 1H), 7.98 (t, 1H,
J = 7.5 Hz), 7.85 (d, 1H, J = 8.5 Hz), 7.72 (t, 1H, J = 7.4 Hz),
7.62 (d, 3H, J = 6.0 Hz), 7.43 (d, 2H, J = 6.8 Hz), 3.77(q, 2H),
3.08 (t, 2H, J = 7.2 Hz), 2.45–2.35 (q, 2H); MS (ESI): m/z = 246
[M+H]+; I.R. (KBr, cmÀ1): 3432, 2906, 2465, 1590.
(ESI): m/z
=
328 [M+H]+; HRMS (ESI) Calculated for
C22H15NCl [M+H]+ 328.0893 found 328.0890; I.R. (KBr,
cmÀ1): 3421, 3051, 2897, 2462, 1635, 1597, 1341.
3-Methyl-2,4-diphenylquinoline (C22H17N, Table 1, entry
17). White solid (M.p. 188–191ꢀC); 1H NMR (300 MHz,
DMSO-d6): d 9.37 (d, 1H, J = 8.7 Hz), 7.83 (t, 3H, J = 6.2 Hz),
7.68–7.50 (m, 8H), 7.42 (d, 2H, J = 6.8 Hz), 2.29 (s, 3H);
Journal of Heterocyclic Chemistry
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R. Venkatesham, A. Manjula, and B. Vittal Rao
Vol 49
2-Methyl-4-phenyl-quinoline-3-carboxylic acid ethylester
m/z = 200 [M+H]+; I.R. (KBr, cmÀ1): 3391, 2629, 2601, 1860,
1704, 1637.
(C19H17NO2, Table 1, entry 1, ref. 13d). White solid (M.p.
98–100ꢀC); 1H NMR (300 MHz, DMSO-d6): d 8.05 (d, 1H,
J = 8.3 Hz), 7.72–7.65 (m, 1H), 7.54 (d, 1H, J = 8.3 Hz),
7.48–7.41 (m, 3H), 7.40–7.33 (m, 3H), 4.06–3.99 (q, 2H),
2.77 (s, 3H), 0.93 (t, 3H, J = 6.8 Hz); MS (ESI): m/z = 292
[M+H]+; I.R. (KBr, cmÀ1): 3399, 2977, 1719, 1235, 1068.
9-Phenyl-3,4-dihydro-2H-acridin-1-one (C19H15NO, Table 1,
entry 14, ref. 13a). White solid (M.p. 154–157ꢀC); 1H NMR
(300 MHz, DMSO-d6): d 8.40 (d, 1H, J = 8.5 Hz), 8.01 (t, 1H,
J = 8.1 Hz), 7.64 (t, 1H, J = 8.2 Hz), 7.57–7.48 (m, 4H),
7.22–7.16 (q, 2H), 2.75 (t, 2H, J = 6.4 Hz), 2.54 (s, 2H),
2.37–2.27 (q, 2H); MS (ESI): m/z = 274 [M+H]+; I.R.
(KBr, cmÀ1): 3387, 2935, 1699, 1631, 1382.
9-Methyl-2,3-dihydro-1H-cyclopenta[b]quinoline (C13H13N,
Table 1, entry 18, ref. 14). Yellow oil 1H NMR (300 MHz,
DMSO-d6): d 8.44–9.35 (m, 1H), 8.24 (d, 1H, J = 7.5 Hz), 7.95
(t, 1H, J = 7.4 Hz), 7.85–7.77 (m, 1H), 3.57 (t, 2H, J = 7.5 Hz),
3.24 (t, 2H, J = 7.2 Hz), 2.84 (s, 3H), 2.47–2.36 (m, 2H); m/z =
184 [M+H]+; I.R. (KBr, cmÀ1): 3326, 2928, 2521, 1595.
Acknowledgments. Authors thank Director, I.I.C.T and Head,
Organic Chemistry Division-II for the facilities, and R.V. thanks
University Grants Commission (UGC), New Delhi, for financial
support.
6-Chloro-2-methyl-4-phenyl-quinoline-3-carboxylic acid
methylester (C18H14NO3Cl, Table 1, entry 8, ref. 13b). White
solid (M.p. 196–198ꢀC); 1H NMR (300 MHz, DMSO-d6):
d 9.23 (d, 1H, J = 9.1 Hz), 7.99 (dd, 1H, J = 9.1 Hz), 7.70
(d, 1H, J = 1.5 Hz), 7.65–7.60 (m, 3H), 7.39–7.35 (m, 2H),
3.62 (s, 3H), 3.25 (s, 3H); MS (ESI): m/z = 312 [M+H]+; I.R.
(KBr, cmÀ1): 3432, 2955, 2374, 1727.
2-(4-Methoxy-phenyl)-4-phenyl-quinoline (C22H17NO, Table 1,
entry 16, ref. 14). Yellow solid (M.p. 74–76ꢀC); 1H NMR
(300 MHz, DMSO-d6): d 8.79 (d, 1H, J = 8.5 Hz), 8.33 (d, 2H,
J = 8.9 Hz), 8.18 (s, 1H), 8.11–8.02 (m, 2H), 7.79 (t, 1H, J =
7.4 Hz), 7.70–7.62 (m, 5H), 7.19 (d, 2H, J = 8.9 Hz), 3.96 (s,
3H); MS (ESI): m/z = 312 [M+H]+; I.R. (KBr, cmÀ1): 3408,
3052, 2844, 1629, 1595, 1244, 1186.
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4-Phenyl-2-thiophene-2-yl-quinoline (C19H13NS, Table 1,
1
entry 15, ref. 14). Pale yellow solid (M.p. 90–92ꢀC); H NMR
(300 MHz, DMSO-d6): d 8.33 (d, 1H, J = 4.5 Hz), 8.13 (d,
1H, J = 3.8 Hz), 7.92–7.79 (m, 3H), 7.68 (d, 1H, J = 5.1 Hz),
7.61–7.52 (m, 6H), 7.24 (t, 1H, J = 3.8 Hz); MS (ESI): m/z =
288 [M+H]+; I.R. (KBr, cmÀ1): 3418, 3028, 2851, 2697, 1626,
1595, 1407, 1367.
9-Phenyl-1,2,3,4-tetrahydro-acridine (C19H17N, Table 1,
1
entry 12, ref. 13d). White solid (M.p. 136–138ꢀC); H NMR
(300 MHz, DMSO-d6): d 8.55 (d, 1H, J = 9.8 Hz), 8.00 (t,1H,
J = 7.5 Hz), 7.70 (t, 1H, J = 7.7 Hz), 7.65–7.58 (m, 3H), 7.55
(d, 1H, J = 8.7 Hz), 7.29 (d, 2H, J = 6.2 Hz), 3.56 (t, 2H, J =
5.7 Hz), 2.71 (t, 2H, J = 6.2 Hz), 2.09–2.0 (q, 2H), 1.93–1.85
(q, 2H); MS (ESI): m/z = 259 [M+H]+; I.R. (KBr, cmÀ1):
3412, 3055, 2930, 2563, 1909, 761, 707.
[9] (a) Mol, W.; Matyia, M.; Filip, B.; Wietrzyk, K.; Boryczka, S.
Bioorg Med Chem 2008, 16, 8136; (b) Ferlin, M. G.; Gatto, G.;
Chiarelotto, G.; Palumbo, M. Bioorg Med Chem 2001, 9, 1843.
[10] Rotzoll, S.; Willy, B.; Schonhaber, J.; Muller, T. J. J Eur J Org
Chem 2010, 3516.
[11] (a) Deorong, D.; Cong-Gui, Z. Eur J Org Chem 2010, 3802;
(b) Zhang, H.; Liao, Y. H.; Yuan, W. C.; Zhang, X. M. Eur J Org Chem
2010, 3215; (c) Matoba, K.; Kawai, H.; Furukawa, T.; Kusuda, A.;
Tokunaga, E.; Nakamura, S.; Shiro, M.; Shibata, N. Angew Chem Int
Ed 2010, 49, 5762.
[12] (a) Margherita B., Stefano, B.; Silvano, C.; Stefano, D.
Tetrahedron Lett 2010, 51, 2342; (b) Cheng-Sheng, S.; Ze, Z.;
Shu-Jiang, T.; Guan-Wu, W. Org Biomol Chem 2006, 4, 104.
[13] (a) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K. Synlett 2004,
963. (b) Fan, J.; Wan, C.; Sun, G.; Wang, Z. J Org Chem 2008, 73, 8608.
(c) Brian, R.; Naughton, Mc.; Benjamin, L. M. Org Lett 2003, 5, 4257; (d)
Yadav, J. S.; Reddy, B. V. S.; Sreedhar, P.; Srinivasa Rao, R.; Nagaiah, K.
Synthesis 2004, 14, 2381; (e) Rei-Sheu, H.; Heuy-Min, W.; Iou-Jiun, K.;
Hau-Dung, D.; Ling-Ching, C. Heterocycles 2010, 81, 689.
[14] Das, B.; Damodar, K.; Chowdhury, N.; Aravind Kumar, R. J.
Mol Catal A: Chem 2007, 274, 148.
2,4-Dimethyl-quinoline-3-carboxylicacid methylester (C13H13
NO2, Table 1, entry 21, ref. 13b). Yellow oil 1H NMR
(300 MHz, DMSO-d6): d 5.92 (d, 1H, J = 8.3 Hz), 5.73
(d, 1H, J = 8.3 Hz), 5.62 (t, 1H, J = 6.8 Hz), 5.41 (t, 1H, J =
7.5 Hz), 1.52 (s, 3H), 0.33 (s, 6H); MS (ESI): m/z = 216
[M+H]+; I.R. (KBr, cmÀ1): 3463, 2945, 2514, 1738, 1230.
2,4-Dimethyl-quinoline-3-carboxylic acid ethylester (C14H15
NO2, Table 1, entry 19, ref. 13b). Yellow oil 1H NMR (300
MHz, DMSO-d6): d 8.45 (d, 2H, J = 8.5 Hz), 8.13 (t, 1H, J =
7.4 Hz), 7.94 (t, 1H, J = 7.7 Hz), 4.57–4.47 (m, 2H), 2.97
(s, 3H), 2.91 (s, 3H), 1.45 (t, 3H, J = 7.0 Hz); m/z = 230
[M+H]+; I.R. (KBr, cmÀ1): 3448, 2982, 2509, 1731, 1300.
1-(2,4-Dimethyl-quinolin-3-yl)-ethanone(C13H13NO, Table 1,
[15] (a) Shailaja, M.; Manjula, A.; Vittal Rao, B. Ind J Chem 2010,
49B, 482; (b) Shailaja. M.; Manjula, A.; Vittal Rao, B. J Sulfur
Chem 2007, 28, 31. (c) Venkatesham, R.; Manjula, A.; Vittal Rao, B. J
Heterocycl Chem 2011, 48, 942.
1
entry 20, ref. 13b). Yellow oil H NMR (300 MHz, DMSO-d6):
d 8.39 (t, 2H, J = 9.1 Hz), 8.06 (t, 1H, J = 7.2 Hz), 7.89
(t, 1H, J = 7.9 Hz), 2.89 (s, 3H), 2.83 (s, 3H), 2.71 (s, 3H);
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet