Synthesis of benzoquinoline derivatives from formyl naphthylamines via Friedl?nder annulation under metal-free conditions

Article abstract of DOI:10.1007/s00706-018-2268-x

Abstract: The synthesis of benzoquinolines and benzoquinolinones via Friedl?nder-type condensation of aminonaphthalene carbaldehydes with (1) primary or secondary alcohols mediated by urea/KOH or with (2) diketones or β-ketoesters is described. The behavi

Full text of DOI:10.1007/s00706-018-2268-x

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-018-2268-x(012 345678,9-(). ov Vl
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ORIGINAL PAPER
Synthesis of benzoquinoline derivatives from formyl naphthylamines
via Friedla¨nder annulation under metal-free conditions
Zbigniew Malinowski1
Emilia Fornal2 Anna Warpas2 Monika Nowak1
•
•
•
Received: 29 March 2018 / Accepted: 1 July 2018
Ó The Author(s) 2018
Abstract
The synthesis of benzoquinolines and benzoquinolinones via Friedlander-type condensation of aminonaphthalene car-
¨
baldehydes with (1) primary or secondary alcohols mediated by urea/KOH or with (2) diketones or b-ketoesters is
¨ ¨
described. The behavior of naphthalene derivatives in the Friedlander annulation, resulted in the formation of Friedlander
¨
or non-Friedlander products, is also presented.
Graphical abstract
¨
Keywords Benzoquinolines Á Benzoquinolinones Á Friedlander synthesis Á Urea Á Formamidation Á Copper(II) coupling
Introduction
and Doebner–Miller [15, 16] or Pfitzinger [17, 18]
methodology. Much attention has been devoted to devel-
oping these synthesis methods by using various carbonyl
components [19–22].
Functionalized quinolines and quinolinones have aroused
strong interest of medicinal and pharmaceutical chemistry,
on account of their diverse biological properties [1–5] such
as, e.g., anti-inflammatory [6, 7], antimicrobial [8, 9],
antioxidant [10], or antitumor [11–14] activity, which
qualify them as excellent targets in therapeutic and
medicinal research. The classical approaches for the
quinoline ring construction involve inter alia Skraup [15]
The aim of the present work is an application of formyl
naphthylamines in the construction of alkyl substituted
benzo[h]- or benzo[f]quinolines B and quinoline-2(1H)-
¨
ones C via Friedlander condensation (Scheme 1). In this
work, we want to shed some light on the mediated by urea/
¨
KOH synthesis of quinolines (Friedlander product) and on
the specific formation of quinoline-2(1H)-ones (non-
¨
Friedlander product) from N-Boc 2-naphthylamine
& Zbigniew Malinowski
zbigniew.malinowski@chemia.uni.lodz.pl
derivatives under basic conditions.
& Monika Nowak
monika.nowak@uni.lodz.pl
Results and discussion
1
Department of Organic Chemistry, Faculty of Chemistry,
University of Lodz, Tamka 12 Str., 91-403 Lodz, Poland
We began our studies from the synthesis of carbamates 2, 7
(Scheme 2) being key compounds in the construction of
the benzoquinoline skeleton. Their synthesis involved the
2
Department of Pathophysiology, Medical University of
Lublin, Jaczewskiego 8b Str., 20-090 Lublin, Poland
123

Z. Malinowski et al.
On the other hand, attempts to obtain bromocarbamate
8, bromoamine 10, or amine 9 ended in failure (Scheme 2).
In all cases, difficult to analyze mixtures were obtained,
which did not contain target products 8 or 9 (1H NMR).
Scheme 1
¨
In the recent years, the indirect variant of Friedlander
reaction has become a very popular wherein both elec-
trophilic and/or nucleophilic components are generated
in situ from appropriate primary and/or secondary alcohols
[26–28]. However, the available in the literature examples
often include the use of frequently expensive catalysts, e.g.,
RuCl2-(DMSO)4 [29–31], RhCl(PPh3)3 [32], and IrCl(-
cod)2 [33]. The alternative approach, described in last
years, can be the aerial oxidation of alcohols to appropriate
carbonyl compounds carried out with air access and with-
out the use of catalyst [34–39].
With the formyl amines 4 and 5 in hand, we focused on
the using of primary and secondary alcohols as a source of
active carbonyl compounds, able to cyclize with 4 or 5 in
the presence of urea and form benzo[h]quinolines 11 via
¨
Friedlander annulations [40–43]. During our earlier studies
on the construction of benzo[h]quinazolin-2(1H)-ones from
1-naphthylamine derivatives with the use of urea as a
condensing agent, we have observed that heating of the
2-formyl-1-naphthylamine with urea/KOH in alcohol
solution can led to the formation of benzo[h]quinoline
skeleton. We began our experiments by investigating the
reaction of 5 with ethanol, in the presence of 1 equiv. KOH
(Table 1, entry 1). Surprisingly, the cyclization process to
11e using these conditions did not take place. With the
increase of amount of KOH to 7 equiv., the yield of ben-
zoquinoline 11e was improved but an influence was not
reactions of the aryllithium species, generated from 2, 7
and t-BuLi or BuLi [23–25], with DMF and provided to
corresponding formyl derivatives 2 and 7 with 60 and 50%
yields, respectively. Next, derivative 2 subjected to
bromination reaction with NBS in acetonitrile used as a
solvent led to bromocarbamate 3 (75%). The subsequent
cleavage of the Boc protecting group of 3 by treatment with
HClaq afforded desired bromoamine 5 in 92% yield. In
turn, the deprotection of N-Boc amine 2, under the same
reaction conditions as above, gave aminoaldehyde 4 in
good, albeit a bit lower 75% yield (Scheme 2).
Scheme 2
123

Synthesis of benzoquinoline derivatives from formyl naphthylamines via Friedländer…
Table 1 Optimization of reaction conditions
Entry
KOH/equiv.
Urea/equiv.
Solv. (5 cm3)
Temp./°C
Time/h
Yield/%a
11
12b
Product 11e, R1 = H
d
d
1b
2b
3b
4b
5b
6b
1
3
7
7
7
7
–
–
–
1
2
3
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
75
75
75
75
75
75
20
20
20
20
20
20
–
–
Tracec
–
6
–
10
–
38
Tracec
45
10
Method A
7
0.20
3
EtOH
75
20
–
–
Product 11g, R1 = Me
8b
9b
10b
7
7
1
3
1
1
i-PrOH
i-PrOH
i-PrOH
75
75
75
20
20
20
60
30
68
25
–
–
Method B
11b
12e
13f
14b,g
15b,g
1
1
1
1
1
–
1
1
1
3
i-PrOH
1,4-Dioxane
DCM
75
80
40
75
75
20
20
20
15
15
6
–
d
d
–
–
d
d
–
–
i-PrOH
i-PrOH
62
60
6
33
aIsolated yield
b5 cm3 EtOH or i-PrOH
1
cYield from H NMR
dNo reaction
e10 equiv. i-PrOH
f3 equiv. i-PrOH
gInert atmosphere (Ar)
spectacular (6%, Table 1, entries 1–3). These results are in
partial contrast with those presented in the literature [34].
It turned out that the addition of urea had a significant
impact on the acceleration as well as the yield of the
condensation process (Table 1, entries 4–6). The use of
urea and base in the molar ratio 3:7 gave 11e in a satis-
factory 45% yield. In this case, a small amount of amino-
benzoquinazoline 12b (10% yield) was also isolated from
post-reaction mixture. The formation of 12b can be an
effect of the competing reaction of 5 with urea under basic
conditions (similarly to the first stage of the Biginelli
reaction) [44–47]. It is notable that the yield of compound
12b was, to some extent, dependent on an amount of urea
(Table 1, entries 4–6). On the other hand, the use of too
little amount of KOH (20 mol%, Table 1, entry 7) did not
give any reaction product. We found that the reaction
worked well not only with EtOH but also with secondary
alcohols (i-PrOH). The condensation of 5 with i-PrOH,
using urea and KOH in the molar ratio 3:7, led to benzo-
quinoline 11g with a good yield (60%, Table 1, entry 8).
Similarly, as in earlier reactions (Table 1, entries 5, 6), the
formation of byproduct 12b (25%) was also observed. The
quantity reduction of amount of urea gave better results.
The compound 11g was produced in 68% yield as the sole
123

Z. Malinowski et al.
reaction product (Table 1, entries 9, 10). Similarly, as in
the case of using ethanol (Table 1, entry 3), the conden-
sation of 5 with i-PrOH performed in the absence of urea
was ineffective (Table 1, entry 11), and resulted in
obtaining 11g in only 6% yield. Also, the application of
other solvents, such as 1,4-dioxane or DCM, was ineffi-
cient (Table 1, entries 12, 13). Finally, we conducted the
reaction between 5 and i-PrOH under an argon atmosphere
(Table 1, entry 14). To our surprise, the cyclization ran
with a similar rate and yield like under air conditions (11g,
62% yield, Table 1, entry 14). Increase in the amount of
urea led to a little decrease in yield of 11g (60%), but
substantial increase in the formation of 12b (33%)
(Table 1, entry 15).
that urea anion can play dual role acting as additional base
and nucleophile [50]. Its nucleophilic activity is strongly
visible especially during the reaction of amino ketone 5
with alcohols (urea and KOH excess), where amino ben-
zoquinazoline 12b is produced as side product (Table 1,
entries 6, 8, 14, 15).
The probable mechanism for the construction of ben-
zoquinazolines using formylamines and alcohols in the
presence of urea was presented below (Scheme 3). We
think that the proposed mechanism is not the only one
possible for these transformations, and it can operate par-
allel with, e.g., the classical pathway presented in the lit-
¨
erature for Friedlander reaction under basic conditions
[51–54].
The mechanism of the formation of benzoquinolines 11
in the reaction between 5 and primary/secondary alcohols,
in the presence of urea/KOH, is not clear, yet. However,
based on the literature reports [48, 49] and results men-
tioned above (Table 1), we suppose that the first step
includes the conversion of alcohols into corresponding
carbonyl compounds. To obtain the additional information
that may help to understand this type of conversion, some
variants of reaction based on the condensation of 5 with
acetone were checked (Table 2, entries 1–5).
Despite the fact that our initial experiments performed
under air atmosphere were not efficient (Table 1, entries
1–3), it cannot entirely omit the path involved aerial oxi-
dation of I (Scheme 3, air [O] path) via the formation of
appropriate hydroperoxides, and next elimination of H2O2,
as it was suggested in the literature [34]. Furthermore, also
an alternative oxidation pathways of I to II by, e.g., H2O2
[34, 55–57] or the Oppenauer oxidation of I [58–60] [rel-
evant notably under anaerobic conditions (argon)], can
have an importance. The observed increase in the reaction
yields upon the addition of urea, suggest that, it facilitates
the formation of quinolines. Our observations suggest that
urea or its anion can participate in the oxidation of I to II
acting as a hydride acceptor and also has an influence on
the reaction between formylamine III and carbonyl com-
ponent II through, e.g., the hydrogen bonds formation
(between urea anion and oxygen atom) activating carbonyl
group to nucleophilic attack (Scheme 3, IV, V) [61]. On
the other hand, nitrogen atoms of urea anion can also act on
the a hydrogens of V or VII through the electronegative
As can be seen from Table 2, the condensation process
of 5 with acetone did not take place only in the presence of
urea (Table 2, entries 1, 2). The use of 1 equiv. of urea and
25%mol of KOH (Table 2, entry 4) in comparison to
reaction without the use of urea (40%, Table 2, entry 3)
gave better result in yield of 11g (60%). These observations
can confirm that urea anion generated by the action of
KOH in polar solvents (alcohols) is an active intermediate
can mediate the cyclization process (Table 2, entry 4).
Information included in Tables 1 and 2 allow to conclude
Table 2 Confirmation of reaction conditions
Entry
KOH/equiv.
Urea/equiv.
Solv. (8 cm3)
Temp./°C
Time/h
Yield/%a
11g
1
2
3
4
5
–
1
3
–
1
–
Acetone
Acetone
Acetone
Acetone
Acetone
75
75
75
75
75
20
20
20
20
0.5
–
–
–
0.25
0.25
7
40
60
80
aIsolated yield
123

Synthesis of benzoquinoline derivatives from formyl naphthylamines via Friedländer…
Scheme 3
pull and the electron density increase at the carbon atom,
making easier nucleophilic attack on the carbonyl carbon
atom [62].
proceeded with the formation of mixtures of 2-substituted
and 2,3-disubstituted benzoquinolines 11c, 11d and 11i,
11j, however, with a low regioselectivity. (The molar ratios
of 11c/11d and 11i/11j were 0.6:1.)
With the best conditions in hand (Table 1, entry 6,
method A, for primary alcohols; entry 10, method B, for
secondary alcohols), next we synthesized series of benzo-
quinoline derivatives 11 (Scheme 4). The cyclization of
non-brominated derivative 4 with EtOH or i-PrOH led to
the formation of corresponding benzoquinolines 11a and
11b in moderate yields, 40 and 33%, respectively (method
A). Beyond these target compounds, just like it was
described for the reaction of 5 with ethanol, some amounts
of amino derivative 12a (3–8%) and also substrate 4
(10–30%) were achieved. In turn, the reaction of n-propyl
alcohol (method A) with 5 gave 3-methylbenzoquinoline
(11f) in much better 65% yield. In this case a small
quantity of aminobenzoquinazoline 12b (about 4%) was
also isolated. Good results were achieved for the reaction
between 5 and cyclopentanol (method B), and in effect, the
tetracyclic derivative 11h was formed in 64% yield. On the
other hand, when unsymmetrical alcohol (sec-butanol) was
employed to the condensation with 4 or 5, the reaction
Unexpectedly, condensation reactions of 4 or 5 per-
formed in ethanol, propan-1-ol, or butan-2-ol, provided
except 11, also 2-methylbenzoquinoline or 6-bromo-2-
methylbenzoquinoline
in
1–7%
yields.
Both
2-methylquinolines were identified by NMR, HRMS
spectroscopy, and by comparison of their NMR spectra
with the data recorded for products 11b, 11g and also
reported in the literature [63, 64]. The formation of unusual
¨
products is sometimes observed in Friedlander reaction
[65, 66].
In the next step, bromobenzoquinolines 11e, 11f, 11h
were subjected to copper(II)-mediated N-formamidation
reaction [67]. The couplings of 11e, 11f, 11h with for-
mamide were carried out without the use of ligand, in the
presence of CuSO4Á5H2O/K2CO3. (Benzo[h]quinolin-6-
yl)formamides 13a–13c were obtained in 62–85% yields
(Scheme 5). The spectroscopic analysis of coupling
123

Z. Malinowski et al.
Scheme 4
Scheme 5
acetoacetate, acetylacetone, and ethyl benzoylacetate
(Scheme 6). Because of using ethanol as a solvent and the
possibility of the course of the competitive condensation
process, KOH was replaced with weaker base K2CO3.
When amino aldehyde 5 was treated with 1 equiv. of ethyl
acetoacetate and 1 equiv. of base in ethanol as a solvent,
the desired product 14a was received in moderate 25%
yield (Scheme 6). In turn, when the amount of ethyl ace-
toacetate was increased up to 10 equiv. target benzo-
quinoline 14a was effectively produced and finally
obtained in an excellent 85% yield. Under similar reaction
conditions, aminoaldehyde 5 condensed with acetylacetone
gave acetylquinoline 14b in 68% yield. The structures of
newly synthesized quinolines 14a, 14b were confirmed by
NMR spectroscopy analyses. In the 13C NMR spectra of
14a and 14b characteristic signals corresponding to carbon
atoms of C=O group of COOMe and Ac substituent were
observed at 166.5 and 199.9 ppm, respectively and signals
of methyl carbon atoms at 2 position were detected at
26.0 ppm. The obtained NMR chemical shift data are in
accordance with the literature ones published for 2,3-di-
products 13 indicated the occurrence the mixture of rota-
mers in the ratio 2.2:1 (1H NMR).
substituted
quinolines
[68–70]
containing
ester
Obtained values of proton coupling constant of the
NHCHO moiety (e.g., for 13c: * 10.2 Hz for trans,
* 1.2 Hz for cis) led to the conclusion that formamide
benzoquinolines general exist in the mixture of two rota-
mers favoring the Z form (Scheme 5).
(166–170 ppm) or acetyl (199–207 ppm) moiety placed at
3 position and methyl group at 2 position (23–26 ppm).
Previously, we have noticed that N-Boc-2-naphthyl-
amine derivatives contrary to N-Boc-1-naphthylamine are
ready for cleavage of the Boc protecting group under basic
conditions [23–25]. This fact has prompted us to extend the
presented methodology and use the carbamate 7 in the
The second part of our work was dedicated to the syn-
¨
thesis of alkyl benzoquinolines via standard Friedlander
reaction conditions using dicarbonyl compounds, e.g., ethyl
cyclization reaction, without
a
prior deprotection
123

Synthesis of benzoquinoline derivatives from formyl naphthylamines via Friedländer…
Scheme 6
(Scheme 6). As we observed, when compound 7 was
treated with ethyl acetoacetate (10 equiv.) in the presence
of K2CO3 (1 equiv.; Scheme 6, 15 h, 70 °C), similarly as
in the case of 5, the target product was not formed. Fur-
thermore, the formation of amine 9 was also not observed.
In 1H NMR spectra of post-reaction mixtures indicated
only signals belonging to unreacted carbamate 7. The
increase in an amount of K2CO3 from 1 to 5 equiv. led,
after 40 h to the mixture of 9 and 7 in the molar ratio 0.84:1
(1H NMR). With evidence to support our ideas in hand, we
used 5 equiv. of K2CO3 suspended in ethanol to the con-
densation of 7 with ethyl acetoacetate.
group and labile hydrogen atom (–OH or –NH). One may
wonder about the possibility of the formation of acid 16a
via hydrolysis of ester 15a [68]. The formation
¨
2-methylquinoline-3-carboxylic acids under Friedlander
reaction conditions is described in literature [71, 72] and
their examples were presented in Table 3 (compounds 19
[73], 20 [74]). It is an important to say here, that in each
case, it was taken for granted that the formation of com-
pounds 19a, 19b, and 20 is a consequence of the hydrolysis
¨
of corresponding ethyl esters produced under Friedlander
annulations [71–74].
In the 13C NMR spectrum of the reaction product of 7
and ethyl acetoacetate (Scheme 6), our attention was drawn
to two carbon atom signals at 197.1 and 160.4 ppm. Very
similar 13C NMR peaks were described for compounds 19a
and 19b (19a: 197.3 and 160.4 ppm; 19b: 203.5 and
159.5 ppm) [73]. In turn, in the 13C NMR spectrum of acid
20 the most downfield carbon signal was situated at
169.0 ppm and was assigned to carbon atom of –COOH
group [74], which seems more likely. It is known, that
typical range of chemical shifts for carbon of –COOH
Similarly as for 5 and in accordance with generally
¨
accepted course of the Friedlander reaction and commonly
available literature reports, from the reaction of 7 with
ethyl acetoacetate (Scheme 6), we expected to receive ester
1
15a. The analysis of H and 13C NMR spectra unexpect-
edly showed no signals which could be assigned to the
1
ester group. Instead, the H NMR spectrum has shown the
presence of two characteristic signals at 2.68 ppm and
12.52 ppm, which could indicate the occurrence of methyl
123

Z. Malinowski et al.
Table 3 13C NMR data
This work
14a (85%)
14b (68%)
17a (85%)
17b (65%)
Literature [73, 74, 79-81]
21a R1 = H, 21b R1 = Me
19a R1 = H, 19b R1 = Me
20
22a R1 = H, 22b R1 = Me
group in aromatic acids is between 159–170 ppm, while for
carbons of –CHO or –COR groups they are usually
observed above 190 ppm [75–78]. The comparison of 13C
NMR spectroscopic data of the obtained product with
compounds 14, 19, and 20 and also with signals from
spectra of quinolinones 21 [79, 80] and 22 [79–81]
(Table 3), led to the conclusion that the reaction of 7 with
ethyl acetoacetate (10 equiv.) in the presence of base (5
equiv.) gives benzoquinolinone 17a (30%). To our delight,
increase an amount of base up to 10 equiv. allowed to
achieve 17a in 85% yield. By contrast, the reaction of 7
with ethyl benzoylacetate led to formation of 17b in 65%
yield under the same reaction conditions. In this case,
similarly to 17a, the 13C NMR spectrum showed specific
peaks located at 194.9 ppm (keton) and 160.8 ppm (lac-
tam) (Table 3). On the other hand when N-Boc derivative 3
(Scheme 2) was treated with ethyl acetoacetate (10 equiv.)
in the presence of 10 equiv. K2CO3 in ethanol, desired
product was not obtained. After reaction unchanged sub-
strates were only isolated, which prove that 3 under these
conditions did not undergo cleavage of protecting group
and consequently amine 5, necessary to completion of the
reaction is not formed. Besides, the reaction of
aminoaldehyde 5 with ethyl acetoacetate (10 equiv.) and
K2CO3 (10 equiv.) in ethanol leads to ester 14a as the only
product (72%, Scheme 6).
In our opinion, the possible mechanism of the formation
of compounds 17 includes 1) in the first step, in situ for-
mation of amine 9 in the presence of base and next 2) the
reaction of 9 with ketoester leading to the intermediate 18
[82], which under basic conditions undergoes intramolec-
ular cyclization yielding quinolinones 17 (Scheme 6)
[74, 79–81, 83]. This transformation to some extent
resembles the Niementowski-type cyclization reaction,
described in literature [84].
Conclusion
In summary, we presented the method for the synthesis of
alkyl benzoquinolines via KOH/urea-mediated indirect
¨
Friedlander reaction of amino naphthalene aldehydes with
aliphatic alcohols. We have found that under aerial as well
as inert atmosphere the method involving the use of urea
may be employed and lead to desired benzoquinolines with
good yields. In addition, we have briefly discussed the
different behavior of 1- and 2-naphthylamine derivatives
during the condensation with dicarbonyl compounds con-
taining active methylene moiety. In result either
123

Synthesis of benzoquinoline derivatives from formyl naphthylamines via Friedländer…
benzo[h]quinoline or benzo[f]quinolinone derivatives were
obtained in also good yields as the major products. In
copper(II) catalyzed N-aryl formamidation reaction, sev-
eral formamide benzoquinolines have been also synthe-
sized. There is no doubt that new formamide
benzoquinolines may constitute excellent starting material
to further modifications.
solution in pentane or BuLi solution in hexanes (2.2 equiv.)
was added dropwise. The reaction mixture was stirred at
this temperature for 2 h. Next, a solution of DMF (1 equiv.)
at - 20 °C was added dropwise and whole was further
stirred for 2 h (- 20 °C). After this time to the reaction
mixture 20 cm3 saturated solution of NH4Cl was added.
The water layer was separated and extracted subsequently
with Et2O (3 9 20 cm3). The organic phase was dried over
MgSO4 and concentrated to dryness. The crude material
was separated by flash chromatography.
Experimental
tert-Butyl (2-formylnaphthalen-1-yl)carbamate (2, C16H18-
NO3) Beige solid (342 mg, 60% yield); Rf = 0.16 (hex/
Melting points were determined on a Boetius hot stage
apparatus. 1H, 13C NMR spectra were recorded on a Bruker
Avance III spectrometer at 600 MHz and 150 MHz. The
residual CDCl3 or DMSO-d6 signal was used for reference
(CDCl3 at 7.26 ppm or DMSO-d6 at 2.54 ppm for 1H NMR
and CDCl3 at 77.0 ppm or DMSO-d6 at 39.0 ppm for 13C
NMR). IR spectra were recorded on a Nicolet Nexus FT-IR
spectrometer. LC/HRMS analyses were performed using
an Agilent Technologies HPLC 1290 coupled to an Agilent
Technologies 6550 Accurate Mass Q-TOF LC–MS mass
spectrometer equipped with a JetStream Technology ion
source housed in the Department of Pathophysiology,
Medical University of Lublin, Poland. Internal mass cali-
bration was enabled; reference ions of m/z = 121.0509 and
922.0098 were used. The analytical thin layer chromatog-
raphy tests (TLC) were carried out on Sigma-Aldrich
(Supelco) silica gel plates (Kiselgel 60 F254, layer thickness
0.2 mm) and the spots were visualized using UV lamp. The
flash column chromatography purifications were performed
on Fluka silica gel (Silica gel 60, 0.040–0.063 mm). t-
Butyllithium or butyllithium solutions (Aldrich) were each
time titrated before use [85]. All reactions with organo-
lithium compounds were performed under an argon atmo-
sphere using standard Schlenk technique. Diethyl ether was
distilled from sodium benzophenone ketyl prior to use.
Commercially available solvents and reagents: N,N-
dimethylformamide (DMF), N-bromosuccinimide (NBS),
EtOH, PrOH, i-PrOH, butan-2-ol, cyclopentanol, urea,
acetylacetone, ethyl acetoacetate, ethyl benzoylacetate,
CuSO4Á5H2O, and formamide were purchased from Sigma-
Aldrich and were used without further purification. N-Boc-
2-naphthylamine (1) and tert-butyl (1-bromonaphthalen-2-
yl)carbamate (6) were prepared by a procedure similar to
that in the literature [23–25].
ꢀ
AcOEt, 10:1); m.p.: 123–125 °C; IR (KBr): m = 3275,
2999, 2983, 2968, 2870, 1720, 1690 cm-1 1H NMR
;
(CDCl3): d = 10.27 (s, 1H, CHO), 8.22–8.05 (m, 2H, NH,
Ar–H), 7.87 (d, J = 7.8 Hz, 1H, Ar–H), 7.84–7.78 (m, 2H,
Ar–H), 7.66–7.56 (m, 2H, Ar–H), 1.53 (s, 9H, Boc–Me)
ppm; 13C NMR (CDCl3): d = 192.4, 154.5, 138.0, 137.0,
129.3, 128.9, 128.4, 126.9, 126.6, 126.0, 125.7, 125.2,
81.7, 28.4 ppm.
tert-Butyl (1-formylnaphthalen-2-yl)carbamate (7, C16H18-
NO3) Lemon solid (210 mg, 50% yield); Rf = 0.44 (PE/
ꢀ
AcOEt, 10:1); m.p.: 107–109 °C; IR (KBr): m = 3433,
2983, 2935, 1723, 1650 cm-1 1H NMR (CDCl3):
;
d = 11.54 (br s, 1H, NH), 11.01 (br s, 1H, CHO), 8.73 (d,
J = 9.3 Hz, 1H, Ar–H), 8.43 (d, J = 8.6 Hz, 1H, Ar–H),
8.02 (d, J = 9.3 Hz, 1H, Ar–H), 7.83 (d, J = 8.0 Hz, 1H,
Ar–H), 7.64–7.58 (m, 1H, Ar–H), 7.48–7.42 (m, 1H, Ar–
H), 1.57 (s, 9H, Boc–Me) ppm; 13C NMR (CDCl3):
d = 192.2, 153.2, 143.8, 137.5, 134.0, 129.5, 129.0 (2C),
124.9, 119.7, 118.2, 112.0, 81.4, 28.4 ppm.
tert-Butyl (4-bromo-2-formylnaphthalen-1-yl)carbamate (3,
C16H17BrNO3) To a solution of the appropriate carbamate
2 (2.5 mmol) in 15 cm3 acetonitrile at 0 °C, a solution of
NBS (3.0 mmol) in 10 cm3 acetonitrile was added drop-
wise. Next, the resulting mixture was allowed to warm to
ambient temperature. The reaction was continued under
these conditions until TLC analysis of the reaction mixture
indicated the absence of starting material 2 (4–6 h). After
the reaction acetonitrile was removed under reduced pres-
sure and the bromo derivative 3 was separated by flash
chromatography. Yellow solid (657 mg, 75% yield);
Rf = 0.32 (hex/AcOEt, 5:1); m.p.: 165–168 °C; IR (KBr):
1
m = 3354, 2969, 2935, 2852, 1701, 1684 cm-1; H NMR
ꢀ
(CDCl3): d = 10.19 (s, 1H, CHO), 8.30–8.26 (m, 1H, Ar–
H), 8.16–8.10 (m, 2H, Ar–H), 7.87 (s, 1H, NH), 7.75 (ddd,
J = 8.3, 6.9, 1.2 Hz, 1H, Ar–H), 7.66 (ddd, J = 8.2, 6.9,
1.2 Hz, 1H, Ar–H), 1.52 (s, 9H, Boc–Me) ppm; 13C NMR
(CDCl3): d = 190.6, 154.3, 137.5, 135.2, 130.7, 130.3,
129.0, 128.0, 127.7, 126.8, 125.4, 121.1, 82.1, 28.3 ppm.
General procedure for the preparation of 1-
formylnaphthalene and 2-formylnaphthalene
carbamates 2 and 7
Under argon, to a solution of N-Boc 1-naphthylamine (1,
2.1 mmol) or tert-butyl (1-bromonaphthalen-2-yl)carba-
mate (6, 1.55 mmol) in 20 cm3 dry Et2O at -20 °C, t-BuLi
123

Z. Malinowski et al.
2-Methylbenzo[h]quinoline (11b) [89, 90] Light orange
solid (11 mg, 33% yield); Rf = 0.68 (hex/AcOEt, 5:1);
m.p.: 38–39 °C (lit. [90], 47–48 °C).
Procedure for the preparation of amino
aldehydes 4, 5
To a mixture of HClaq (0.5 M) and 1,4-dioxane in the ratio
2:3 (v/v) at room temperature, aldehyde (2 or 3, 1.6 mmol)
was added. The resulting mixture was then heated at 60 °C
(oil bath) for about 3–4 h, until TLC analysis indicated the
completion of the reaction. Then all the volatile materials
were removed under reduced pressure and 15 cm3 water
was added to residue. The mixture was adjusted to pH 7–8
with saturated NaHCO3 and extracted with chloroform
(3 9 20 cm3). The combined extracts were dried over
MgSO4 and then concentrated. A crude residue was sub-
jected to column chromatography to give amines 4 and 5.
Mixture of 2-ethylbenzo[h]quinoline (11c) [91] and 2,3-
dimethylbenzo[h]quinoline (11d) [92, 93] Light yellow
solid (36 mg, 38% yield (11c) and 60% yield (11d); Rf
= 0.6 (for both compounds; hex/AcOEt, 5:1).
6-Bromobenzo[h]quinoline (11e) [94, 95] Beige solid
(23 mg, 45% yield); Rf = 0.84 (hex/AcOEt, 1:1); m.p.:
105–107 °C (lit. [95], 109–111.5 °C).
6-Bromo-3-methylbenzo[h]quinoline
(11f,
C14H11-
BrN) Yellow solid (35 mg, 65% yield); Rf = 0.64 (hex/
ꢀ
AcOEt, 5:1); m.p.: 114–115 °C; IR (KBr): m = 2924, 2852,
1595 cm-1; 1H NMR (CDCl3): d = 9.31–9.27 (m, 1H, Ar–
H), 8.84 (d, J = 2.0 Hz, 1H, Ar–H), 8.34–8.29 (m, 1H, Ar–
H), 7.99 (s, 1H, Ar–H), 7.86–7.84 (m, 1H, Ar–H),
7.79–7.75 (m, 2H, Ar–H), 2.56 (s, 3H, Me) ppm; 13C NMR
(CDCl3): d = 150.9, 144.1, 134.3, 132.7, 132.2, 131.7,
128.8, 128.7, 128.0, 127.6, 126.6, 124.6, 122.7, 18.8 ppm.
1-Aminonaphthalene-2-carbaldehyde (4) [86] Yellow
solid (205 mg, 75% yield); Rf = 0.3 (hex/AcOEt, 5:1);
m.p.: 99–101 °C (lit. [86], 97–100 °C).
1-Amino-4-bromonaphthalene-2-carbaldehyde (5, C11H9-
BrNO) Yellow solid (368 mg, 92% yield); Rf = 0.32 (hex/
ꢀ
AcOEt, 5:1); m.p.: 165–168 °C; IR (KBr): m = 3306, 2751,
1
1637 cm-1; H NMR (CDCl3): d = 9.89 (s, 1H, CHO),
6-Bromo-2-methylbenzo[h]quinoline (11g) [96] Light
yellow solid (35 mg, 68% yield); Rf = 0.62 (hex/AcOEt,
5:1); m.p.: 92–94 °C (lit. [96], 101–103 °C).
8.22–8.19 (m, 1H, Ar–H), 7.93 (d, J = 8.4 Hz, 1H, Ar–H),
7.76 (s, 1H, Ar–H), 7.75–7.71 (m, 1H, Ar–H), 7.60–7.55
(m, 1H, Ar–H), 7.36 (s, 2H, NH2) ppm; 13C NMR (CDCl3):
d = 192.5, 148.7, 134.9, 132.9, 130.9, 128.3, 126.5, 124.1,
122.3, 113.3, 108.4 ppm.
5-Bromo-9,10-dihydro-8H-benzo[h]cyclopenta[b]quinoline
(11h, C16H13BrN) Yellow solid (38 mg, 64% yield); Rf
= 0.45 (hex/AcOEt, 5:1); m.p.: 105–107 °C; IR (KBr):
-1
;
1H NMR
ꢀ
m = 3030, 2959, 2920, 2855, 1596 cm
General procedure for the preparation
of benzoquinolines 11
(CDCl3): d = 9.37–9.31 (m, 1H, Ar–H), 8.32–8.26 (m, 1H,
Ar–H), 7.98 (s, 1H, Ar–H), 7.83–7.81 (m, 1H, Ar–H),
7.76–7.72 (m, 2H, Ar–H), 3.26–3.21 (m, 2H, CH2),
The reaction was carried out in the open air conditions
(vessels with air supply). To a mixture of amino aldehyde
(4 or 5, 0.2 mmol) and KOH (7 equiv. in case of the
reaction with primary alcohols or 1 equiv. with secondary
alcohols) in 10 cm3 of appropriate alcohol, urea was added
(3 equiv. for reaction with primary alcohols or 1 equiv.
with secondary alcohols). The whole mixture was stirred
and heated at 75 °C (oil bath) until TLC analysis indicated
the absence of substrate 4 or 5. After the reaction was
completed, alcohol was removed under reduced pressure
and 15 cm3 water was added to residue. The mixture was
adjusted to pH 7–8 with 0.5 M HCl and then extracted with
DCM (3 3 20 cm3). The combined extracts were dried
over MgSO4 and concentrated, and a crude mixture was
purified by flash chromatography to give desired benzo-
quinoline 11.
3.15–3.11 (m, 2H, CH2), 2.30–2.21 (m, 2H, CH2) ppm; 13
C
NMR (CDCl3): d = 167.0, 145.0, 136.9, 132.7, 131.7,
129.9, 129.2, 128.6, 127.6, 127.4, 125.6, 124.7, 121.2,
35.0, 30.8, 23.8 ppm.
Mixture of 6-bromo-2-ethylbenzo[h]quinoline (11i, C15H13-
BrN) and 6-bromo-2,3-dimethylbenzo[h]quinoline (11j,
C15H13BrN) Yellow solid (43 mg, 30% yield (11i) and
54% yield (11j)); Rf = 0.78 (for both compounds; hex/
1
AcOEt, 1:1); H NMR (CDCl3): d = 9.44–9.40 (m, 1H,
Ar–H), 9.36–9.32 (m, 1H, Ar–H), 8.34-8.27 (m, 2H, Ar–H,
Ar–H), 8.01 (s, 1H, Ar–H), 7.98-7.96 (m, 1H, Ar–H), 7.96
(s, 1H, Ar–H), 7.80–7.72 (m, 5H, 3Ar–H, 2Ar–H), 7.40 (d,
J = 8.5 Hz, 1H, Ar–H), 3.09 (q, J = 7.6 Hz, 2H, CH2),
2.76 (s, 3H, Me), 2.48 (s, 3H, Me), 1.49 (t, J = 7.6 Hz, 3H,
CH2Me) ppm; 13C NMR (CDCl3): d = 163.2, 158.0, 145.4,
143.6, 135.2, 134.7, 132.7, 132.5, 132.1, 131.7, 131.3,
128.9, 128.8, 128.5, 128.5, 127.7, 127.6, 127.4, 125.6,
125.0, 124.9, 124.6, 124.6, 121.9, 121.4, 121.3, 32.3, 23.9,
19.6, 13.7 ppm.
Benzo[h]quinoline (11a) [87] Light orange solid (14 mg,
40% yield); Rf = 0.54 (hex/AcOEt, 5:1); m.p.: 46–47 °C
(lit. [88], 49–51 °C).
123

Synthesis of benzoquinoline derivatives from formyl naphthylamines via Friedländer…
Benzo[h]quinazolin-2-amine (12a, C12H10N3) White solid
(1.2–3 mg, 3–8% yield); Rf = 0.07 (hex/AcOEt, 5:1); m.p.:
127.2, 125.8, 124.3, 124.1, 122.9, 122.6, 121.9, 116.8,
115.8 ppm.
ꢀ
194–196 °C; IR (KBr): m = 3336, 3184, 2926, 2854,
N-(3-Methylbenzo[h]quinolin-6-yl)formamide (13b, C15H13-
N2O) White solid (35 mg, 85% yield); Rf = 0.24 (hex/
1
1651 cm-1; H NMR (CDCl3): d = 9.06 (d, J = 8.0 Hz,
1H, Ar–H), 8.97 (s, 1H, Ar–H), 7.86–7.82 (m, 1H, Ar–H),
ꢀ
AcOEt, 1:1); m.p.: 221–223 °C; IR (KBr): m = 3435, 3193,
7.73–7.69 (m, 1H, Ar–H), 7.68–7.63 (m, 1H, Ar–H), 7.55
1
(s, 2H, Ar–H), 5.28 (s, 2H, NH2) ppm; H NMR (DMSO-
3101, 2948, 2919, 2876, 1701 cm-1; 1H NMR (DMSO-d6;
mixture of rotamers in the ratio 2.2:1*): d = 10.58 (d,
J = 10.1 Hz, 1H, NH*), 10.40 (br. s, 1H, NH), 9.27–9.19
(m, 2H, Ar–H, Ar–H*), 8.83–8.77 (m, 2H, Ar–H, Ar–H*),
8.70 (d, J = 10.1 Hz, 1H, CHO*), 8.57 (br. s, 1H, CHO),
8.33 (br. s, 1H, Ar–H), 8.29–8.24 (m, 1H, Ar–H),
8.24–8.19 (m, 1H, Ar–H*), 8.16–8.10 (m, 2H, Ar–H, Ar–
H*), 7.83–7.76 (m, 4H, 2Ar–H, 2Ar–H*), 7.70 (br. s,
1H, Ar–H*), 2.51 (s, 6H, Me, Me*) ppm; 13C NMR
(DMSO-d6): d = 163.9, 160.6, 149.8, 149.7, 142.0, 141.4,
134.7, 134.6, 132.6, 132.0, 131.5, 131.4, 131.3, 128.1,
128.0, 127.9, 127.5, 127.2, 125.7, 125.5, 124.1, 123.9,
122.8, 121.9, 116.7, 115.7, 18.0 ppm.
d6): d = 9.05 (s, 1H), 8.91 (d, J = 8.2 Hz, 1H), 7.93 (d,
J = 7.9 Hz, 1H), 7.77–7.71 (m, 1H), 7.69–7.63 (m, 2H),
7.58–7.54 (m, 1H), 6.93 (s, 2H, NH2) ppm; 13C NMR
(CDCl3): d = 161.1, 160.7, 152.6, 136.1, 130.0, 129.4,
128.0, 126.8, 124.8, 124.2, 123.6, 117.5 ppm.
6-Bromobenzo[h]quinazolin-2-amine (12b, C12H9BrN3)
Light orange solid (2.2–14 mg, 4–25% yield); Rf = 0.5
ꢀ
(hex/AcOEt, 1:1); m.p.: 223–225 °C; IR (KBr): m = 3479,
3285, 3166, 2925, 2853, 1623, 1606 cm-1 1H NMR
;
(DMSO-d6): d = 9.06 (s, 1H, Ar–H), 9.00 (d, J = 8.0 Hz,
1H, Ar–H), 8.16 (d, J = 8.2 Hz, 1H, Ar–H), 8.13 (s, 1H,
Ar–H), 7.92–7.88 (m, 1H, Ar–H), 7.80–7.75 (m, 1H, Ar–
H), 7.13 (s, 2H, NH2) ppm; 13C NMR (DMSO-d6):
d = 161.8, 160.4, 151.1, 133.3, 130.9, 129.9, 127.7, 127.3,
126.8, 124.4, 116.5, 114.6 ppm.
N-(9,10-Dihydro-8H-benzo[h]cyclopenta[b]quinolin-5-yl)form-
amide (13c, C17H15N2O) Light yellow solid (28 mg, 62%
yield); Rf = 0.32 (hex/AcOEt, 1:1); m.p.: 247–249 °C; IR
1
(KBr): m = 3433, 3232, 2959, 1687, 1663 cm-1; H NMR
ꢀ
(DMSO-d6; mixture of rotamers in the ratio 2.2:1*):
d = 10.52 (d, J = 10.2 Hz, 1H, NH*), 10.35 (br s,
1H, NH), 9.26–9.20 (m, 2H, Ar–H, Ar–H*), 8.66 (d,
J = 10.2 Hz, 1H, CHO*), 8.55 (d, J = 1.2 Hz, 1H, CHO),
8.30 (br. s, 1H, Ar–H), 8.24–8.20 (m, 1H, Ar–H),
8.20–8.16 (m, 1H, Ar–H*), 8.11 (br. s, 2H, Ar–H*, Ar–H),
7.79–7.74 (m, 4H, 2Ar–H, 2Ar–H*), 7.72 (br. s, 1H, Ar–
H*), 3.18–3.13 (m, 4H, 2Ar–H, 2Ar–H*), 3.13–3.07 (m,
4H, 2Ar–H, 2Ar–H*), 2.23–2.14 (m, 4H, 2Ar–H, 2Ar–H*)
ppm; 13C NMR (DMSO-d6): d = 165.5, 165.4, 163.8,
160.5, 141.0, 142.8, 142.3, 136.5, 131.5, 131.4, 131.3,
130.2, 128.1, 127.7, 127.6, 127.2, 127.1, 126.8, 124.4,
124.3, 124.1, 124.0, 122.7, 121.8, 117.7, 116.7, 34.0, 30.0,
23.1 ppm.
General procedure for the preparation
of formamide derivatives of benzoquinoline 13
via copper-mediated N-formamidation
Benzoquinoline 11e or 11f or 11h (0.18 mmol), CuSO4Á-
5H2O (2.5 equiv.) and K2CO3 (5 equiv.) suspended in
15 cm3 formamide was heated with magnetic stirring at
140 °C (oil bath) for about 25 h until TLC analysis indi-
cated the absence of starting benzoquinoline. After cooling
to the reaction mixture, 20–30 cm3 water with ice was
added and allowed to stand for 30 min. After this time
mixture was extracted with DCM. The combined extracts
were dried over MgSO4 and concentrated to give crude
product 13 which was next subjected to flash
chromatography.
General procedure for the preparation
N-(Benzo[h]quinolin-6-yl)formamide
(13a,
C14H11N2-
of bromobenzoquinolines 14
O) White solid (27 mg, 70% yield); Rf = 0.42 (hex/
ꢀ
AcOEt, 1:2); m.p.: 214–216 °C; IR (KBr): m = 3434, 3228,
To a mixture of the amino aldehyde 5 (0.2 mmol) and
K2CO3 (1 equiv.) in 20 cm3 ethanol ethyl acetoacetate or
acetylacetone (10 equiv.) was added. The whole being then
heated at 70 °C (oil bath) until TLC analysis of the reaction
mixture indicated the absence of starting material 5
(* 25 h). The precipitated crude product 14a or 14b was
filtered from the solution, washed with 10 cm3 water, air-
dried, and next purified by flash chromatography or
crystallization.
3044, 2928, 2890, 1683, 1658 cm-1; 1H NMR (DMSO-d6;
mixture of rotamers in the ratio 2.2:1*): d = 10.61 (d,
J = 10.0 Hz, NH*), 10.44 (br s, 1H, NH), 9.33–9.23 (m,
2H, Ar–H, Ar–H*), 8.99–8.90 (m, 2H, Ar–H, Ar–H*),
8.73 (d, J = 10.0 Hz, 1H, CHO*), 8.59 (s, 1H, CHO), 8.42
(s, 1H, Ar–H), 8.40–8.34 (m, 2H, Ar–H, Ar–H*),
8.31–8.23 (m, 2H, Ar–H, Ar–H*), 7.87–7.78 (m, 5H, 2Ar–
H, 3Ar–H*), 7.70–7.63 (m, 2H, Ar–H, Ar–H*) ppm; 13C
NMR (DMSO-d6): d = 163.8, 160.6, 148.5, 148.4, 143.4,
135.6, 135.5, 131.5, 131.4, 131.3, 128.4, 128.4, 127.6,
Ethyl
6-bromo-2-methylbenzo[h]quinoline-3-carboxylate
(14a, C17H15BrNO2) White solid (58 mg, 85% yield);
123

Z. Malinowski et al.
Rf = 0.75 (DCM/PE, 10:1); m.p.: 145–147 °C; IR (KBr):
m = 3004, 2981, 2927, 1726, 1608 cm
129.8, 129.3, 128.8, 128.5, 128.0, 125.0, 121.7, 117.5,
112.1 ppm.
-1
;
1H NMR
ꢀ
(CDCl3): d = 9.44–9.40 (m, 1H, Ar–H), 8.65 (s, 1H, Ar–
H), 8.36–8.31 (m, 1H, Ar–H), 8.08 (s, 1H, Ar–H),
7.85–7.78 (m, 2H, Ar–H), 4.47 (q, J = 7.1 Hz, 2H, CH2),
3.09 (s, 3H, Me), 1.47 (t, J = 7.1 Hz, 3H, Me) ppm; 13C
NMR (CDCl3): d = 166.5, 158.5, 146.7, 138.3, 133.1,
131.8, 130.1, 128.6, 128.2, 127.7, 125.6, 124.8, 124.3,
122.5, 61.6, 25.9, 14.5 ppm.
Acknowledgements This work was partially supported by the
University of Lodz.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://creative
commons.org/licenses/by/4.0/), which permits unrestricted use, dis-
tribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
made.
1-(6-Bromo-2-methylbenzo[h]quinolin-3-yl)ethanone (14b,
C16H13BrNO) White solid (43 mg, 68% yield); crystal-
lization (PE/DCM, 4:1); m.p.: 188–189 °C; IR (KBr):
-1
;
1H NMR
ꢀ
m = 2995, 2972, 2927, 1682, 1592 cm
References
(CDCl3): d = 9.40–9.37 (m, 1H, Ar–H), 8.38 (s, 1H, Ar–
H), 8.35–8.32 (m, 1H, Ar–H), 8.07 (s, 1H, Ar–H),
7.85–7.78 (m, 2H, Ar–H), 3.00 (s, 3H, Me), 2.73 (s, 3H,
Me) ppm; 13C NMR (CDCl3): d = 199.9, 157.4, 146.4,
136.5, 133.0, 131.9, 131.8, 130.1, 128.5, 128.2, 127.7,
125.6, 124.1, 122.6, 29.5, 26.0 ppm.
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General procedure for the preparation
of benzo[f]quinolin-3(4H)-ones 17
To a mixture of the carbamate 7 (0.4 mmol) and K2CO3
(10 equiv.) in 10 cm3 ethanol ethyl acetoacetate or ethyl
benzoylacetate (10 equiv.) was added. The resulting mix-
ture was then heated at 70 °C (oil bath), until TLC analysis
indicated the completion of the condensation process
(* 15 h). The precipitated solid was filtered from the
solution, washed with 10 cm3 water, air-dried, and next
purified by flash chromatography to give product 17.
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15. Yamashikin SA, Oreshkina EA (2006) Chem Heterocycl Compd
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2-Acetylbenzo[f]quinolin-3(4H)-one
Light yellow solid (81 mg, 85% yield); Rf = 0.26 (hex/
(17a,
C15H12NO2)
AcOEt, 1:2); decomposition above 300 °C; IR (KBr):
1
m = 3003, 2928, 2797, 1682, 1628, 1561 cm-1; H NMR
ꢀ
(DMSO-d6): d = 12.52 (s, 1H, NH), 9.17 (s, 1H, Ar–H),
8.54 (d, J = 8.4 Hz, 1H, Ar–H), 8.15 (d, J = 9.0 Hz, 1H,
Ar–H), 7.98 (d, J = 7.8 Hz, 1H, Ar–H), 7.75–7.68 (m, 1H,
Ar–H), 7.59–7.55 (m, 1H, Ar–H), 7.52 (d, J = 9.0 Hz, 1H,
Ar–H), 2.68 (s, 3H, Me) ppm; 13C NMR (DMSO-d6):
d = 197.1, 160.4, 140.9, 137.9, 134.6, 129.7, 129.0, 128.8,
128.6, 127.8, 125.5, 121.6, 115.8, 111.7, 30.6 ppm.
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19. Prajapati SM, Patel KD, Vekariya RH, Panchal SN, Patel HD
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2-Benzoylbenzo[f]quinolin-3(4H)-one (17b, C20H14NO2)
Yellow solid (78 mg, 65% yield); Rf = 0.46 (AcOEt);
ꢀ
decomposition above 300 °C; IR (KBr): m = 3010, 2928,
2866, 2797, 1662, 1629 cm-1 1H NMR (DMSO-d6):
;
20. Ranu BC, Hajra A, Dey SS, Jana U (2003) Tetrahedron 59:813
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