Convenient route to 2 H -pyrrolo[3,4- b ]quinolin-9(4 H)-one skeleton via tosmic reaction

Article abstract of DOI:10.1080/00397911.2011.622062

A practical and versatile method for the synthesis of 2H-pyrrolo[3,4-b] quinolin-9(4H)-one skeleton via tosylmethyl isocyanide (TosMIC) reaction has been developed. Many attempts have been made to reverse the null reactivity of 4-hydroxyquinoline and its N-alkyl derivatives toward TosMIC reactant. For this reason various molecular modifications have been improved for the purpose of obtaining a reactive substrate. tert-Butyl-4-oxoquinoline-1(4H)-carboxylate resulted in the best substrate to provide the desired tricyclic system via facile TosMIC reaction.

Full text of DOI:10.1080/00397911.2011.622062

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Convenient Route to 2H-Pyrrolo[3,4-
b]quinolin-9(4H)-one Skeleton via TosMIC
Reaction
Federica Rosi a , Giuliana Cuzzucoli Crucitti a , Alberto Iacovo a
,
Gaetano Miele a , Luca Pescatori a , Roberto Di Santo a & Roberta
Costi a
a Istituto Pasteur Fondazione-Cenci Bolognetti, Dipartimento di
Chimica e Tecnologie del Farmaco, Sapienza Università di Roma,
Rome, Italy
Accepted author version posted online: 27 Feb 2012.Version of
record first published: 07 Jan 2013.
To cite this article: Federica Rosi , Giuliana Cuzzucoli Crucitti , Alberto Iacovo , Gaetano Miele ,
Luca Pescatori , Roberto Di Santo & Roberta Costi (2013): Convenient Route to 2H-Pyrrolo[3,4-
b]quinolin-9(4H)-one Skeleton via TosMIC Reaction, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 43:7, 1063-1072
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Synthetic Communications1, 43: 1063–1072, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.622062
CONVENIENT ROUTE TO 2H-PYRROLO
[3,4-b]QUINOLIN-9(4H)-ONE SKELETON
VIA TOSMIC REACTION
Federica Rosi, Giuliana Cuzzucoli Crucitti,
Alberto Iacovo, Gaetano Miele, Luca Pescatori,
Roberto Di Santo, and Roberta Costi
Istituto Pasteur Fondazione-Cenci Bolognetti, Dipartimento di Chimica e
`
Tecnologie del Farmaco, Sapienza Universita di Roma, Rome, Italy
GRAPHICAL ABSTRACT
Abstract
A practical and versatile method for the synthesis of 2H-pyrrolo
[3,4-b]quinolin-9(4H)-one skeleton via tosylmethyl isocyanide (TosMIC) reaction
has been developed. Many attempts have been made to reverse the null reactivity of
4-hydroxyquinoline and its N-alkyl derivatives toward TosMIC reactant. For this reason
various molecular modifications have been improved for the purpose of obtaining a reactive
substrate. tert-Butyl-4-oxoquinoline-1(4H)-carboxylate resulted in the best substrate to
provide the desired tricyclic system via facile TosMIC reaction.
Keywords Heteroaromatic; microwave; quinoline; TosMIC
INTRODUCTION
Our interest in the chemistry of heteroaromatic systems[1a–c] endowed with
biological activities[2a,b] led us to investigate the possibility of obtaining novel poly-
cyclic systems as interesting building blocks. In particular, we decided to focus our
attention on the synthesis of pyrroloquinoline systems[3a,b] because of the wide
involvement in antineoplastic research of tricyclic systems containing one or more
heteroatoms.[4a–d]
Recently, we showed an efficient route to obtain 2H-pyrrolo[3,4-c]quinoline,[3a]
and our interest on this ring system led us to investigate the possibility of obtaining
the 2H-pyrrolo[3,4-b]quinoline isomer. A number of synthetic pathways to obtain
this derivative have been reported.[5a–c] However, these syntheses are difficult to
Received June 24, 2011.
Address correspondence to Luca Pescatori or Roberta Costi, Istituto Pasteur Fondazione-Cenci
`
Bolognetti, Dipartimento di Chimica e Tecnologie de Farmaco, Sapienza Universita di Roma, P. le
Aldo Moro 5, I-00185, Rome, Italy. E-mail: lucapescatori82@gmail.com; roberta.costi@uniromal.it
1063

1064
F. ROSI ET AL.
Figure 1. Synthetic approach to obtain 2H-pyrrolo[3,4-b]quinolin-9(4H)-one derivatives.
carry out and the products obtained from these synthetic pathways take on their
structures a substituent on the pyrrole nitrogen, which in a such a case is not ready
for further chemical reactions.
With the aim to overcome this limit, we designed a synthetic pathway based on
the tosylmethyl isocyanide (TosMIC) reaction carried on quinoline-4(1H)-one (Fig. 1).
RESULTS AND DISCUSSION
Because basic conditions to generate nucleophile were needed, the
quinoline-4(1H)-one must be protected on a nitrogen atom before reaction with
TosMIC. Thus, following Ho and Jones,[6] who conducted the TosMIC reaction
on N-methyl-quinolin-2(1H)-one to obtain the 2H-pyrrolo[3,4-c]quinoline isomer,
we tried a similar approach on the N-ethyl-quinolin-4(1H)-one to obtain 2
(Scheme 1). Despite our expectations, the reaction between 1a and TosMIC reagent
in standard conditions did not occur. In fact, derivative 2 was not isolated from
reaction and starting material 1a was totally recovered after workup.
Our first hypothesis about this inertia was related to the different relative
positions of the nitrogen atom, double carbon–carbon bond, and carbonylic group
of N-alkyl-quinolin-4(lH)-one if compared to N-alkyl-quinolin-2(lH)-one.
Thus we decided to use a few protecting groups on the nitrogen atom, different
from ethyl moiety (Fig. 2). N-Acetyl and N-mesyl quinolinone (1b and 1c, respectively)
were demonstrated to be not stable during the TosMIC reaction. In fact, after the
appropriate reaction time, only 4-hydroxyquinoline (1) was isolated. These results
were probably due to the strong basic conditions produced by the presence of sodium
hydride, needed to perform the TosMIC deprotonation. Conversely, N-Boc
quinolinone (1d) was stable in the presence of sodium hydride and able to react with
TosMIC reagent, giving 2a.
Compound
R group
Yield (%)
1b
1c
1d
CH3CO
CH3SO2
(CH3)3COC
5
12
94
=
O
Taking into account these results, we hypothesized that the nucleophilic
attachment by the deprotonated TosMIC on C2 of the quinolinone was facilitated
by the presence of an electron-withdrawing group bonded to the nitrogen atom of
quinolinone, which improved the electrophilicity of the C2 of the quinolinone
derivative 1d. Thus, the substitution of the ethyl group with the electron-withdrawing

PYRROLOQUINOLINONE DERIVATIVES
1065
Scheme 1. Incompatibility of TosMIC reaction with N-ethyl-quinolin-4(1H)-one (1a).
Figure 2. Protecting group for quinolone nitrogen atom tested for activation toward TosMIC reaction.
Boc functionality has reversed the substrate reactivity by reducing the electronic
density on the nitrogen atom.
Once we identified the Boc as an efficient activating group, we tried to optimize
reaction conditions and final yield, so 1d was submitted to the TosMIC reaction in
different conditions (Table 1).
However, every attempt to directly obtain tert-butyl 9-oxo-2H-pyrrolo
[3,4-b]quinoline-4(9H)-carboxylate (2a) in good yield was unsuccessful. In fact, in
all described conditions, after TosMIC reaction the conversion of reagent to give
products was very poor and the starting material 1d was recovered in high amounts.
The results outlined in Table 1 are influenced by the fact that TosMIC itself is not
fully stable in the presence of certain bases like NaH,[7a] so to improve the yield of
reaction it is not possible to increase reaction time and=or temperature. In every
attempt, the bifunctionalized compound 2b was always obtained in poor yield as
1
the main converted product (Scheme 2). The infrared (IR), H NMR spectra, and
electrospray ionization–mass spectographic (ESI-MS) analyses of derivative 2b
demonstrated the presence of Boc groups linked to the nitrogen atoms of both
quinoline and pyrrole rings.
Therefore, we decided to optimize the yield in compound 2b and to remove
the Boc protection in a second step. At first, 1 eq of quinoline 1d was reacted with
Figure 3. Degradation product.

1066
F. ROSI ET AL.
Table 1. Reaction condition for TosMIC annulation
Ratioa
No. TosMIC Base
Yield (%)
Base type
Solvent
T (ꢀC)
1
2a 2b 2c
1
2
3
4
5
1.1
1.1
1.1
1.1
1.1
1.1 NaH
2.2 NaH
Et2O=DMSO
Et2O=DMSO
Et2O=DMSO
DME
0
0
3
4
0.3
0.7 11
30
0.3 0.8
7
0
0
2.2 NaH
2.2 NaH
2.2 n-buthyl lithium
rt
1.5
2
2
0
rt
0
55
THF
ꢁ50
0
2
3
aRatios are referred to 1 eq of quinolinone 1d.
1.1 eq of TosMIC and 2.2 eq of NaH, at 0 ꢀC using Et2O=dimethylsulfoxide
(DMSO). These conditions gave us 2b in 7% yield (Table 1, entry 1). This yield
was increased using 2.2 eq of NaH (11% yield, Table 1, entry 2) and rose again
using 2.2 eq of NaH and performing the reaction at room temperature. In this
case, 2b was obtained with the best yield (30%, Table 1, entry 3). One more
attempt was conducted to increase this value, following the procedure described
by van Leusen[7a,b] that involves the use of dimethoxyethane (DME) as solvent,
Scheme 2. TosMIC reaction conducted on N-Boc quinoline 1d with variable conditions.

PYRROLOQUINOLINONE DERIVATIVES
1067
Scheme 3. Microwave-assisted Boc removal from derivative 2b.
but the yields of 2b were less than in other cases (0.8%, Table 1, entry 4). Further
attempts to increase the yields of TosMIC reaction were performed by changing
the solvent and the base. Thus, n-buthyllithium as a base (2.2 eq) and tetrahydro-
furan (THF) as the reaction solvent have been used at ꢁ50 ꢀC (Table 1, entry 5). In
this case, behind 2a (2%) and 2b (3%), also the tosyl derivative 2c was obtained as
the major product (55%, Table 1, entry 5).
Once the tricyclic system was obtained through the synthesis of 2b, our studies
were focused on the removal of the Boc protecting groups. Many experimental
conditions were used for both Boc removal: classic acidic conditions and microwave-
assisted method. Using trifluoroacetic acid, p-toluenesulfonic acid, or ZnCl2, the
main recovered product was the degradation product that was hypothesized to be
1
3 based on H NMR and MS spectra (see Fig. 3).
Thus, we tried a more selective approach to remove only one Boc protecting
group. Many efficient methods to cleave the Boc group on solid support have been
described.[8a–c] In our laboratories, an efficient microwave-assisted method that led
to derivative 2a starting from derivative 2b was developed (Scheme 3). In particular,
SiO2 or clay K-10 were used as compounds having both functions as solid matrixes
and acidic catalysts.
Using clay K-10, the yield of reaction was of 14% (Table 2, entry 1), whereas
using SiO2 the yield was increased up to 36% (Table 2, entry 2). This value was
further enhanced by treating 2b with SiO2 in milder conditions (60 W, 60 ꢀC). These
conditions were applied for 5 ꢂ 3 min=cycle, obtaining 2a with a final yield of 55%
(Table 2, entry 3). Once we obtained 2a, we try to convert it to the desired product
2H-pyrrolo[3,4-c]quinolin-9(4H)-one using the same microwave-assisted method
developed by us (Table 2, entry c), but unfortunately also in this case the main
recovered product was the degradation product 3.
We concluded that 2H-pyrrolo[3,4-c]quinolin-9(4H)-one could be instable and
the loss of both Boc functionalities causes the breaking of the pyrrole ring.
Table 2. Reaction condition for microwave-assisted Boc removal
Entry
Solid matrix
Conditions
Yield
1
2
3
Clay K-10
SiO2
SiO2
100 W=100 ꢀC 1 cycle of 1 min
100 W=120 ꢀC 1 cycle of 1 min
60 W=60 ꢀC 3 cycles of 5 min
14
36
55

1068
F. ROSI ET AL.
CONCLUSIONS
The pyrroloquinolinone derivative 2a was obtained with few synthetic steps by
the using of TosMIC reagent on quinolinone ring. The TosMIC reaction was
accomplished on a substrate that presents acetyl, mesyl, or Boc as protecting groups
the on nitrogen atom of the quinolinone ring. The Boc moiety resulted in the most
stable protecting group to perform this reaction in the presence of sodium hydride.
Furthermore, the presence of an electron-withdrawing group. like Boc functionality,
activates the substrate 1d toward TosMIC reagent.
The implementation of microwave reaction for the Boc removal enhanced the
yield of 2a considering the short reaction time needed. Moreover, in this case the use
of SiO2 as solid matrix coupled with a multicycle microwave reaction was more
efficient than the use of clay K-10.
These experimental conditions allow us to remove specifically the Boc
functionality present on the pyrrole system with a yield up to 55%.
EXPERIMENTAL
Melting points were determined on a Bibby Stuart Scientific SMP1 melting-point
apparatus and are uncorrected. Infrared (IR) spectra (Nujol mulls) were recorded on a
1
Perkin-Elmer Spectrum One spectrophotometer. H NMR spectra were recorded at
400 MHz on a Bruker AC 400 Ultrashield 10 spectrophotometer (400 MHz). Mass
spectra were obtained with a Hewlet-Packard 5989B mass spectrometer equipped with
an analytical (Bradford, CT) electrospray ion source and ion guide. LC=MS=MS1
spectra were obtained using
a Micromass (Manchester, UK) Quattro II
triple-quadrupole mass spectrometer equipped with an electrospray ionization detec-
tor and a Hewlett-Packard 1050 HPLC system. Dimethylsulfoxide-d6 99.9% (code
44,139-2) and deuterochloroform 98.8% (code 41,675-4) of isotopic purity (Aldrich)
were used. The solvent column chromatographies were performed on silica gel (Merck;
70–230 mesh) column or alluminium oxide (Sigma-Aldrich; 150 mesh) column. All
compounds were routinely checked by thin-layer chromatography (TLC) by using
aluminium-backed silica-gel plates (Fluka DC-Alufolien Kieselgel 60 F254) or
aluminium oxide (Fluka DC-Alufolien Aluminium oxide). Developed plates were
visualized by ultraviolet (UV) light. Solvents were reagent grade and, when necessary,
were purified and dried by standard methods. Concentration of solutions after reac-
tions and extractions involved the use of rotary evaporator (Buchi) operating at a
¨
reduced pressure (ca. 20 Torr). Organic solutions were dried over anhydrous sodium
sulfate (Merck). All reactions were carried out under nitrogen; all solvents were freshly
distilled under nitrogen and stored over molecular sieves for at least 3 h prior to use.
Synthesis of 1-Ethylquinolin-4(1H)-one (1a)
Potassium carbonate (1.90 g, 13.78 mmol, 2 eq) and iodoethane (2.23 mL,
27.56 mmol, 4 eq) were added to a stirred solution of 1 (1.03 g, 6.89 mmol) in
dimethylformamide (DMF) (30 mL). The reaction was stirred at 90 ꢀC overnight.
The mixture was treated with water and extracted with chloroform. The organic
layer was washed with brine and dried over anhydrous sodium sulfate. The solvent

PYRROLOQUINOLINONE DERIVATIVES
1069
was evaporated to give 900 mg of oil, which was purified by chromatography on
aluminium oxide (ethyl acetate=ethanol 10:1 as eluent) to give 730 mg of 1a as white
solid (61% yield).[9]
Synthesis of 1-Acetylquinolin-4(1H)-one (1b)
A solution of acetyl chloride in dichloromethane (5.75 mL, 33% v=v) was
added dropwise to a cooled (5 ꢀC) and stirred suspension of 1 (2 g, 13.78 mmol) in
dichloromethane (7.2 mL). The reaction was stirred at room temperature for
20 min. The solvent was evaporated, and the residue was dissolved in ethyl acetate,
washed with water and brine, and dried over anhydrous sodium sulfate. The organic
layer was concentrated and purified by chromatography on silica gel (ethyl acetate as
1
eluent) to give 120 mg of 1b as colorless oil (5% yield). H NMR (CDCl3) d 8.36 (d,
J ¼ 8.5 Hz, 1H), 7.86 (d, J ¼ 7.1 Hz, 1H), 7.68 (d, J ¼ 8.5 Hz, 1H), 7.61 (t, J ¼ 7.1 Hz,
1H), 7.37 (t, J ¼ 7.5 Hz, 1H), 6.41 (d, J ¼ 7.2 Hz, 1H), 2.15 (s, 3H); IR n 1771 (CO),
1623 (CO). Elemental analysis for C11H9NO2, calc. C, 70.58; H, 4.85; N, 7.48; O,
17.09; found C, 70.39; H, 4.91; N, 7.57; O, 17.15.
Synthesise 1c and 1d
Triethylamine (1.45 mL, 10.34 mmol, 1.5 eq), the opportune alkylating agent
(10.34 mmol, 1.5 eq), and dimethylaminopyridine (DMAP) (catalytic amount) were
added to a cooled and stirred suspension of 1 (1 g, 6.89 mmol) in anhydrous
tetrahydrofuran (250 mL). The reaction was stirred at room temperature for 2 h.
The mixture was concentrated, and the residue was solubilized with ethyl acetate.
The organic layer was washed with water and dried over anhydrous sodium sulfate.
The solvent was evaporated, and the crude product was purified by chromatography
on aluminium oxide (chloroform as eluent).
1-Mesyl-quinoline 4(1H)-one (1c). As alkylating agent, mesyl chloride (1.2 g,
1
10.34 mmol, 1.5 eq) afforded 0.18 g of 1c as a colorless oil (12% yield). H NMR
(CDCl3) d 8.45 (d, J ¼ 8.0 Hz, 1H), 8.30 (d, J ¼ 8.5 Hz, 1H), 8.27 (d, J ¼ 8.5 Hz,
1H), 7.78 (t, J ¼ 8.0 Hz, 1H), 7.53 (t, J ¼ 8.0 Hz, 1H), 6.36 (d, J ¼ 8.5 Hz, 1H), 3.41
(s, 3H); IR n 1619 (CO). Elemental analysis for C10H9NO3S, calc. C, 53.80; H,
4.06; N, 6.27; O, 21.50; S, 14.36; found C, 53.72; H, 4.17; N, 6.15; O, 21.48; S, 14.33.
tert-Butyl 4-oxoquinoline-1(4H)-carboxylate (1d). As alkylating agent, di-
tert-buthyl-dicarbonate (2.2 g, 10.34 mmol, 1.5 eq) afforded 1.59 g of 1d as a colourless
oil (94% yield). 1H NMR (CDCl3) d 8.59 (d, J¼ 8.5 Hz, 1H), 8.38 (d, J ¼ 7.5 Hz, 1H),
8.31 (d, J ¼ 8.5 Hz, 1H), 7.66(t, J ¼ 8 Hz, 1H), 7.43 (t, J¼ 7.5 Hz, 1H), 6.26(d, J ¼ 8.5 Hz,
Hz, 1H), 1.69 (s, 9H); IR n 1737 (CO), 1649 (CO). Elemental analysis for C14H15NO3,
calc. C, 68.56; H, 6.16; N, 5.71; O, 19.57; found C, 68.67; H, 6.10; N, 5.62; O, 19.70.
Synthesis of tert-Butyl 9-oxo-2H-Pyrrolo[3,4-b]quinoline-4(9H)-
carboxylate (2a)
The SiO2 solid support (1 g, 10:1 w=w) was added to a solution of Boc
derivative 2b (0.1 g, 0.2 mmol) in chloroform (10 mL). The solvent was evaporated,

1070
F. ROSI ET AL.
and residue was moved into a vial for microwave reactor. The reaction was conduc-
ꢀ
ted at 60 C with a power of 60 W. These conditions were applied for 5 ꢂ 3 min=
cycle. After the reaction time the solid was washed with tetrahydrofuran to give a
crude product, which was purified by chromatography on aluminium oxide (10:1
ethyl acetate–ethanol as eluent). After chromatography, 2a was obtained as colorless
oil with an yield of 55%. 1H NMR (CDCl3) d 10.40 (bs, 1H), 8.44 (d, J ¼ 8.0 Hz, 1H),
8.22 (d, J ¼ 8.5 Hz, 1H), 7.61 (t, 2H), 7.33 (t, J ¼ 7.5 Hz, 2H), 1.69 (s, 9H); IR n 1725
(CO), 1626 (CO); HR-ESIMS (m=z): (M þ H)þ 285. Elemental analysis for
C16H16N2O3, calc. C, 67.59; H, 5.67; N, 9.85; O, 16.88; found C, 67.67; H, 5.59;
N, 9.88; O, 16.95.
Synthesis of Di-tert-butyl-9-oxo-2H-pyrrolo[3,4-b]quinoline-2,4-(9H)-
dicarboxylate (2b)
A solution of 1d (1.33 g, 5.42 mmol) and toluene-4-sulfonylmethylisocyanide
(1.16 g, 5,96 mmol, 1.1 eq) in a mixture of anhydrous dimethyl sulfoxide=ethyl ether
(14:30 mL) was added dropwise into a well-stirred suspension of sodium hydride
(60% in paraffine oil; 0.48 g, 11.93 mmol, 2.2 eq) in dry ethyl ether (30 mL) under
an argon atmosphere. After the addition, the mixture was stirred at room tempera-
ture for 1 hour. The reaction was treated with water and extracted with ethyl ether.
The organic layer was washed with brine, dried over anhydrous sodium sulfate, and
concentrated to give 1.12 g of dark oil, which was purified by chromatography on
aluminium oxide (chloroform=petroleum ether 2:1 as eluent) to afford 150 mg of
1
2b as yellowish oil (30% yield). H NMR (CDCl3) d 8.36 (d, J ¼ 8.0 Hz, 1H), 8.18
(d, J ¼ 8.5 Hz, 1H), 8.02 (d, J ¼ 2.5 Hz, 1H pyrrole), 7.69 (d, J ¼ 2.5 Hz, 1H pyrrole),
7.61 (t, J ¼ 8.5 Hz, 1H), 7.32 (t, J ¼ 7.5 Hz, 1H), 1.72 (s, 9H), 1.68 (s, 9H); IR n 1748
(CO), 1726 (CO); HR-ESIMS (m=z): (M þ H)þ 385; (M-C4H9)þ 329; (M-C8H18)þ
273; (M-C9H18O2)þ 229; (M-C10H18O4)þ 185; IR n 1748 (CO), 1726 (CO), 1649
(CO). Elemental analysis for C21H24N2O5, calc. C, 65.61; H, 6.29; N, 7.29; O,
20.81; found C, 65.72; H, 6.21; N, 7.35; O, 20.84.
Synthesis of tert-Butyl-9-oxo-1-tosyl-9,9a-dihydro-1H-pyrrolo[3,4-b]
quinoline-4(2H)-carboxylate (2c)
A solution of toluene-4-sulfonylbenzylisocyanide (1.48 g, 7.58 mmol, 1.1 eq) in
anhydrous tetrahydrofuran (15.8 mL) was added dropwise under an argon atmos-
phere to a cooled (ꢁ60 ꢀC) and well-stirred suspension of n-buthyllithium (2.5 M
in n-hexane; 6.1 mL, 15.16 mmol, 2.2 eq) in the same solvent (32 mL). Successively
1d (1.69 g, 6.89 mmol) was dissolved in anhydrous tetrꢀahydrofuran (160 mL) and
then added dropwise. The reaction was stirred at ꢁ50 C for 30 min under argon
flow. The solvent was evaporated under reduced pressure, and the residue was
treated with water and extracted with ethyl acetate. The organic layer was washed
with brine and dried on anhydrous sodium sulfate to give 2.5 g of crude product,
which was directly purified by column chromatography on Al2O3 using ethyl acetate
as eluent. The obtained products were analysed by ESI-MS, IR, and NMR
1
spectroscopy. H NMR (CDCl3) d 10.40 (bs, 1H), 7.89 (d, J ¼ 12.8 Hz, 1H), 7.53
(d, J ¼ 8 Hz, 2H), 7.41 (d, J ¼ 7.5 Hz, 1H), 7.22 (t, J ¼ 7.5 Hz, 1H), 6.92 (d,

PYRROLOQUINOLINONE DERIVATIVES
1071
J ¼ 8.0 Hz, 2H), 6.85 (t, J ¼ 7.5 Hz, 1H), 5.56 (d, J ¼ 12.8 Hz, 1H), 2.15 (s, 3H), 1.38
(s, 9H); IR n 1740 (CO), 1635 (CO); HR-ESIMS (m=z): (MþHþ)þ 439. Elemental
analysis for C23H22N2O5S, calc. C, 63.00; H, 5.06; N, 6.39; O, 18.24; S, 7.31; found
C, 63.07; H, 5.11; N, 6.33; O, 18.30; S, 7.25.
Synthesis of 2-(Aminomethyl)quinoline-3,4-dione (3)
The SiO2 solid support (1.5 g, 10:1 w=w). was added to a solution of Boc
derivative 2a (0.1 g, 0.3 mmol) in chloroform (10 mL). The solvent was evaporated,
and residue was moved into a vial for microwave reactor. The reaction was
conducted at 60 ꢀC with a power of 60 W. These conditions were applied for
5 ꢂ 3 min=cycle. After the reaction time, the solid was washed with tetrahydrofuran
to give a crude product, which was purified by chromatography on aluminium oxide
(ethyl acetate as eluent). After chromatography, 3 was obtained as colorless oil with
1
yield of 53%. H NMR (DMSO-d6) d 8.99 (s, 1H), 8.18 (d, J ¼ 8.0 Hz, 1H), 7.78 (d,
J ¼ 8.5 Hz, 1H), 7.62 (t, J ¼ 7.5 Hz, 1H), 7.31 (t, J ¼ 7.0 Hz, 1H), 4.21 (s, 2H), 1.79 (s,
1H); IR n 1627 (CO), 1663 (CO); HR-ESIMS (m=z): (M þ H)þ 189; (M-C3H3N2O)þ
105. Elemental analysis for C10H8N2O2, calc. C, 63.82; H, 4.28; N, 14.89; O, 17.00;
found C, 63.89; H, 4.21; N, 14.96; O, 16.94.
ACKNOWLEDGMENT
The authors thanks Italian MIUR for financial support under PRIN 2008
(2008CE75SA).
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1. (a) Di Santo, R.; Costi, R.; Massa, S.; Artico, M. Synthesis of
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1
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