Reduction of 3-aminoquinoline-2,4(1H,3H)-diones and deamination of the reaction products

Article abstract of DOI:10.1002/hlca.201300319

3-Aminoquinoline-2,4-diones were stereoselectively reduced with NaBH ₄ to give cis-3-amino-3,4-dihydro-4-hydroxyquinolin-2(1H)-ones. Using triphosgene (=bis(trichloromethyl) carbonate), these compounds were converted to 3,3a-dihydrooxazolo[4,5-

Full text of DOI:10.1002/hlca.201300319

Helvetica Chimica Acta – Vol. 97 (2014)
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Reduction of 3-Aminoquinoline-2,4(1H,3H)-diones and Deamination of the
Reaction Products
by Antonꢀn Kla´sek*a), Antonꢀn Lycˇkab)c), Michal Rouchala), Ondrˇej Rudolfa), and Alesˇ Ru˚zicˇkad)
ˇ
a) Department of Chemistry, Faculty of Technology, Tomas Bata University, CZ-762 72 Zlꢀn
(e-mail: klasek@ft.utb.cz)
b) Research Institute for Organic Syntheses (VUOS), Rybitvꢀ 296, CZ-53354 Pardubice
c
´
´
´
´
) University of Hradec Kralove, Faculty of Science, CZ-500 03 Hradec Kralove 3
d) Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of
Pardubice, CZ-53210 Pardubice
3-Aminoquinoline-2,4-diones were stereoselectively reduced with NaBH4 to give cis-3-amino-3,4-
dihydro-4-hydroxyquinolin-2(1H)-ones. Using triphosgene (¼ bis(trichloromethyl) carbonate), these
compounds were converted to 3,3a-dihydrooxazolo[4,5-c]quinoline-2,4(5H,9bH)-diones. The deamina-
tion of the reduction products using HNO2 afforded mixtures of several compounds, from which 3-alkyl/
aryl-2,3-dihydro-1H-indol-2-ones and their 3-hydroxy and 3-nitro derivatives were isolated as the
products of the molecular rearrangement.
Introduction. – Recently, we reported that the reduction of 3-hydroxyquinoline-
2,4-diones 1 with NaBH4 proceeds in a highly stereoselective manner to give cis-diols 2.
These compounds undergo rearrangement through the action of H2SO4 via an
intermediate carbocation A to 4-alkyl/aryl-3-hydroxy-1H-quinolin-2-ones 3. Starting
with the 3-benzyl derivatives of 1, 4-unsubstituted 3-hydroxy-1H-quinolin-2-ones 4 can
be obtained (Scheme 1) [1].
Scheme 1
The ease and high stereoselectivity of the reduction of diones 1 to diols 2, and their
facile pinacol-pinacoline-type rearrangement to compounds 3 or 4, which pertains to
the synthesis of biologically active viridicatin alkaloids [2 – 6] (if R2 ¼ aryl), prompted
us to study the analogous reactions of 3-aminoquinoline-2,4(1H,3H)-diones 5 (cf.
Scheme 2). We found that the reduction of 5 with NaBH4 also proceeds with high
stereoselectivity and in high yields, but the subsequent deamination of 6 with HNO2 is a
complex reaction leading to a mixture of several products.
ꢁ 2014 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Results and Discussion. – For our experiments, we selected NaBH4 as the reduction
agent. The starting 3-aminoquinoline-2,4(1H,3H)-diones 5a – 5i were prepared by the
reaction of the corresponding 3-chloroquinoline-2,4(1H,3H)-diones with NH3 gener-
ated in situ according to a well-tested protocol [7]. In addition to the seven known
compounds 5, two novel amines 5f and 5i were prepared. Notably, the yields of these
amines with a Bn group at C(3) were much lower than those of the amines with a Ph or
Bu group at C(3) [7], and a considerable quantity of 3-hydroxy derivatives 1 was
simultaneously obtained from this reaction.
Although many 3-aminoquinoline-2,4(1H,3H)-diones 5 are known, their reduction
to the corresponding amino alcohols 6 (cf. Scheme 2) had not been described in the
literature until recently. According to the literature, 25 reductions of a-amino ketones
bearing a NH2 group at a tertiary C-atom to the corresponding 2-amino alcohols were
accomplished using different reagents; however, primarily the reactions with NaBH4
[8 – 13] were successful. To determine the influence of the R2 substituent on the
transformation of diones 5, we selected compounds with the Ph, Bu, and Bn groups in
this position. The H, Me, and Ph groups were selected as the R1 substituents.
Scheme 2
The results of the reduction of compounds 5 with NaBH4 are compiled in Table 1.
All of the reductions exhibited only one spot in TLC in several solvent systems. In the
NMR spectra of the reaction products, only one set of signals was observed, indicating
that the reaction proceeded with high stereoselectivity to give only one of the two

Helvetica Chimica Acta – Vol. 97 (2014)
Table 1. Reduction of Compounds 5a – 5i.
597
Entry
Starting compound
R1
R2
Product (yield [%])a)
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
5e
5f
5g
5h
5i
H
H
H
Me
Me
Me
Ph
Ph
Ph
Bu
Ph
Bn
Bu
Ph
Bn
Bu
Ph
Bn
6a (75)
6b (80)
6c (75)
6d (73)
6e (90)
6f (75)
6g (69)
6h (78)
6i (80)
a) The yields of pure recrystallized compounds.
possible diastereoisomers. This situation was completely analogous to that reported in
our previous publication [1] for the derivatives with OH instead of NH2 at C(3)
(compare Schemes 1 and 2). The NOESY spectra of compounds 6 were recorded to
determine the mutual orientation of the substituents at C(3) and C(4). The results
strongly supported the through-space proximity of the H-atom at C(4) with the H-
atoms of the R2 substituent, evidenced by the appropriate cross-peaks in the NOESY
spectra. However, additional cross-peaks were also observed, because compounds 6 are
not completely rigid, and the dynamic behavior of the substituents at C(3) and C(4)
(rotamers) give rise to additional cross-peaks. The reactions of compounds 6 with
triphosgene (¼ bis(trichloromethyl) carbonate) afford compounds 7, confirming the
cis-configuration of the NH2 and OH groups in 6.
Compounds 6 were analyzed by two MS methods with differing ionization
techniques, electron impact (EI) and electrospray ionization (ESI). In the first-order
EI-mass spectra of compounds 6a, 6d, and 6g (R2 ¼ Bu), and 6b, 6e, and 6h (R2 ¼ Ph),
the peak of the molecular radical cation, Mþ., was unambiguously detected. On the
other hand, in the EI-mass spectra of compounds with a Bn group at C(3), i.e., 6c, 6f,
and 6i, the peak of the molecular ion, Mþ., was not observed, and the most abundant
peak was at the m/z corresponding to the [M ꢀ Bn]þ. fragment. The ESI-MS
experiments of compounds 6 were performed in the positive-ion mode. In the first-
order mass spectra, one dominant signal at m/z corresponding to the [M þ H]þ ion was
observed for all of the examined compounds. In most of the cases, this signal was
accompanied by that for the Naþ adduct [M þ Na]þ and signals approximately twice as
high for [2M þ H]þ and/or [2M þ Na]þ. Moreover, in the first-order mass spectra of
compounds 6a, 6d, and 6g (R2 ¼ Bu), and 6b, 6e, and 6h (R2 ¼ Ph), additional signals
were detected. Using tandem mass spectrometry (under collision-induced dissociation
conditions) of the [M þ H]þ ion, these signals were attributed to the singly charged
fragments of the precursor ion originating from consecutive neutral losses of NH3
([M þ H ꢀ NH3]þ) and CO ([M þ H ꢀ NH3 ꢀ CO]þ). While the latter product ion
peak was observed in the ESI-mass spectra of compounds bearing both Bu and Ph
substituents at C(3), the [M þ H ꢀ NH3]þ ion peak was detected only in the spectra of
compounds 6b, 6e and 6h (R2 ¼ Ph). These signals were completely absent in the first-
order mass spectra of compounds with a Bn group at C(3) (6c, 6f and 6i).

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When a substituted a-amino alcohol is treated with HNO2, its deamination is
accompanied by rearrangement to form a ketone or an aldehyde; in some cases, the
glycol corresponding to the amino alcohol is produced in varying yields [14]. The
deamination of a-amino alcohols bearing a primary NH2 group at the secondary C-
atom to provide an intermediate carbocation is called the ꢃsemipinacolinicꢄ deami-
nation [15]. The deamination of these types of a-amino alcohols with HNO2 was
studied in detail from 1923 to 1960, and this topic has been well-reviewed [16].
However, we were not able to find any analogous reaction involving the deamination of
a compound with a OH group at the secondary C-atom and an NH2 group at the tertiary
C-atom. In this sense, the rearrangement of compounds 6 is exceptional.
In contrast to diols 2, for which two different carbocations can form in the reaction
with H2SO4 [1], the deamination of amino alcohols 6 with HNO2 can result in only one
carbocation B (Scheme 2). This carbocation can react with a nucleophile (possibly
H2O, or AcOꢀ or NOꢀ2 ions) to generate the corresponding 3,4-dihydro-4-hydroxy-
quinolin-2(1H)-ones substituted with OH, AcO, or NO2 group at C(3). A further
possibility is its deprotonation to yield 4-hydroxy-1H-quinolin-2-ones 8. The molecular
rearrangement of B can proceed through the migration of the aryl group in B (C(4a)) to
C(3) to form aldehyde C. However, preliminary analyses of the products of the
molecular rearrangement of 6 indicated that none of the molecules contain an
aldehyde function.
Unfortunately, the deamination of compounds 6 yielded complex mixtures of
several compounds according to TLC, and their separation was very difficult. This
result is the main reason for the relatively low yields of isolated compounds (Table 2).
The main reaction products were identified as 3-alkyl/aryl-2,3-dihydro-1H-indol-2-ones
9, indicating that decarbonylation of the primarily formed intermediate C occured
during the rearrangement. All of the isolated compounds 9 are known, but some of
them have been insufficiently described. Therefore, we determined their spectroscopic
characteristics (Exper. Part). In only one case, 6h, the rearranged product 9h was not
isolated.
In addition to compounds 9 and starting compounds 6, 4-hydroxy-1H-quinolin-2-
ones 8 were obtained (Table 2). In Scheme 2, it is shown that the reaction pathway also
proceeds through deprotonation of intermediate B. Compounds 8 do not form when
the substituent R2 in 6 is a Ph group. Through deamination of these compounds (i.e., 6b,
6e, and 6h), additional compounds were isolated (Table 2). According to elemental
analysis, compounds containing an ONO or NO2 group are present. Differentiation
between these two possibilities was accomplished by studying the chemical shifts of
C(3) in their 13C-NMR spectra. In the literature, the signal of an sp3-C-atom bearing
both a C¼O and a ONO group appears in the region of 82 – 84 ppm [17]. In analogous
compounds, bearing a NO2 group instead of a ONO group, the chemical shift of the
sp3-C-atom is detected in the region of 92 – 96 ppm [18][19]. The compounds that we
isolated exhibit signals in the region from 94.4 – 94.9 ppm, which is consistent with
structure 10. Only two compounds of this type are known in the literature [20]. These
compounds were prepared by oxidation of the corresponding 3-alkylindoles with
thallium(III) trinitrate, but their NMR spectra were not reported. Structure 10 was
finally confirmed through X-ray diffraction analysis of compound 10h; the ORTEP
view of this compound shows a NO2 group at C(3) (Fig.). Compound 10h crystallizes as

Helvetica Chimica Acta – Vol. 97 (2014)
Table 2. Rearrangement of Compounds 6
599
Entry Starting
compound
R1
R2
Methoda) Products (yield [%])b)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
6a
H
H
H
Bu
Ph
Bn
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
8a (11)c), 9a (24)
8a (13)c), 9a (23)
6b
6c
6d
6e
6f
6g
6h
6i
9b (3), 10b (31), 13b (4)
6b (21)d), 9b (9), 10b (7), 11b (8)
8c (11)c), 9c (28)
8c (15)c), 9c (35)
Me Bu
Me Ph
Me Bn
6d (10)d), 9d (51)
6d (13)d), 9d (42)
2e (1)c), 9e (5), 10e (28), 13e (2)
2e (2)c), 9e (11), 10e (12), 13e (2)
8f (4)c), 9f (40)
6f (7)d), 8f (7)c), 9f (28)
6g (28)d), 9g (46)
Ph
Ph
Ph
Bu
Ph
Bn
2g (3)c), 6g (27)d), 9g (39)
10h (4), 11h (13), 12h (3), 13h (6)
2h (3)c), 6h (5)d), 10h (16), 11h (9), 12h (8), 13h (3)
6i (21)d), 8i (16)c), 9i (23)
6i (13)d) 8i (9)c), 9i (26)
a) Method A: NaNO2 in AcOH, urea was added at the end of the reaction; Method B: as Method A, but
without urea addition. b) The yields of pure recrystallized or distilled compounds. c) Identical in all
respects to the authentic sample. d) Recovered starting material.
¯
a racemic mixture in the triclinic space group P1 with two molecules within the unit cell.
From the selected bond distances and angles, the typical features of the aromatic
C(3)ꢀC(4) bond, as well those showing the peptidic character of NꢀC(¼O) moiety and
NO2 group were deduced. Unfortunately, the only slightly similar but comparable
molecules are two 7-nitro-6-oxo-3,4,6,7,8,9-hexahydroimidazo[4,5-f]indolizin-8a-car-
boxylates [21], in which the same arrangement of the NO2 group at the aliphatic
stereogenic center of a five-membered ring is present.
In the first-order positive-ion-mode ESI-MS spectra of compounds 10, the most
abundant peak was attributed to the [M þ H ꢀ NO2]þ. ion originating from in-source
fragmentation of the [M þ H]þ ion, of which the peak was not observed in the mass
spectra. On the other hand, other even-electron ions such as [M þ Na]þ and [M þ K]þ
were formed under ESI conditions. Additionally, the last two ions undergo in-source
fragmentation to give the [M þ Na ꢀ NO2]þ. and [M þ K ꢀ NO2]þ. ions.
Further isolated compounds, indicating the presence of a OH group in their IR
spectra, were identified as 11, mainly from the chemical shifts of C(3) at 77.2 and
77.4 ppm. In the ESI-mass spectra of compounds 11, five significant signals were
observed. The base peak, which we assigned to the [M þ H ꢀ H2O]þ ion, was
accompanied by those of the [M þ Na]þ and [M þ K]þ ions. Moreover, peaks of two
types of singly charged dimeric [2M þ Na]þ and doubly charged trimeric [3M þ Ca]2þ
ions were also detected.
These results indicate that the primary products of the rearrangement of compound
6 are most likely compounds 9, which result from decarbonylation of intermediate C

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Helvetica Chimica Acta – Vol. 97 (2014)
Figure. The molecular structure of compound 10h, ORTEP view (50% probability level). Selected
interatomic distances [ꢅ] and angles [8]: O1ꢀC1, 1.2063(16); C1ꢀC2, 1.5588(18); C2ꢀC3, 1.5047(16);
C3ꢀC4, 1.3935(17); N1ꢀC4, 1.4162(16); N1ꢀC1, 1.3697(17); N2ꢀC2, 1.5510(16); N2ꢀO2, 1.2220(15);
N2ꢀO3, 1.2112(15); O1ꢀC1ꢀN1, 127.06(12); C1ꢀN1ꢀC4, 110.89(11); O2ꢀN2ꢀO3, 124.66(12).
(Scheme 2). Independent of the method, compounds 10 are formed from nitration of 9
with HNO3, which is the product of the decomposition of HNO2 with H2O [22][23].
However, these compounds originate only from 9b, 9e, and 9h, which have a Ph group
at C(3), which facilitates the replacement of an H-atom with the NO2 group.
Compounds 11 are hydrolytic products of 10. Nucleophilic replacement of the aliphatic
tertiary NO2 group in a-position to the C¼O group with a OH moiety proceeds easily
not only under alkaline conditions [24], but also by heating in AcOH [25][26].
However, we cannot exclude that at least a portion of 11 is formed by direct oxidation
of 9.
Interestingly, compounds 12h and 13h were also obtained in low yields from the
rearrangement of 6h. The occurrence of compound 12h evidences that nitration of the
aromatic nucleus can proceed under the given reaction conditions not only at C(3), but
also at C(6). In the literature, only one compound of this type, namely 1,3-dimethyl-3-
[b-(dimethylamino)ethyl]-6-nitroindolinone, has been described as the product from
nitration of the corresponding indolinone [27].

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601
Dimeric compounds 13b, 13e, and 13h resulted from dehydrogenation of the
corresponding compounds 9. The spontaneous dimerization of crude 3-substituted 2,3-
dihydro-1H-indol-2-ones to produce a 3,3’-leucoisoindigo such as 13 has been described
[17]. Several compounds 13, including 13b and 13e, were prepared, in addition to
dioxindoles 11, by oxidation of the corresponding oxindoles 9 with O2 in the presence of
CoII Schiffꢄs base complexes [28]. A dimer similar to 13 was also prepared by the
reaction of 3-[(ethoxycarbonyl)methyl]indolin-2-one enolate with CI4 and was used as
a starting material for the synthesis of the alkaloid (ꢁ)-folicanthine [29]. Both the 1H-
and 13C-NMR spectra of dimeric compounds 13b, 13e, and 13h were very complex.
They consisted of very broad signals that became narrower when the spectra were
recorded at 360 K, and the original shape was observed again after cooling to 300 K.
Hindered rotation due to the presence of bulky substituents is most likely responsible
for this behavior.
Two methods were applied for the deamination of compounds 6 (Table 2). These
methods differ only in that the addition of urea, which was used in Method A (NaNO2
in AcOH) to quench the excess HNO2, was omitted in Method B. However, as shown in
Table 2, there are no substantial differences between the methods in most cases. Our
presumption about the potential reduction of 10 with urea proved to be groundless.
To establish the origin of compounds 10 and 11, we performed additional
experiments. Compound 9h, which we prepared as described in [30], was reacted
with HNO2 under the conditions of Method C (procedure as in Method A, but the
charge of NaNO2 was doubled, and the reaction time was prolonged). After separation
of the crude reaction product by column chromatography (CC; SiO2), the starting
compound 9h and three additional compounds, identified as 10h, 12h, and 13h, were
obtained. This result confirmed our assumption that compounds 10 result from 9 via
nitration with HNO3 produced from HNO2 decomposition. Interesting results were
obtained when the reaction of 9h was performed in the presence of HNO3 (Method D,
procedure as in Method A, but concentrated HNO3 was added instead of H2O, and the
reaction time was prolonged). Starting compound 9h was not isolated, and, in addition
to compound 11h, which was the main reaction product, compound 10h and a
considerable quantity of 6-NO2 derivative 12h were obtained. The formation of
compounds 11 from 10 was established by hydrolyzing 10h with aqueous AcOH in the
presence of urea. In addition to 11h, a small quantity of 9h was obtained, evidencing
that the reduction of 10h with urea also occurs, but only to a small extent at an elevated
temperature.
Conclusions. – The described diastereoselective reduction of 3-aminoquinoline-
2,4(1H,3H)-diones 5 represents an straightforward access to the previously unknown
cis-amino alcohols 6. The molecular rearrangement during their deamination with
HNO2 offered an alternative pathway to not only 3-alkyl/aryl-2,3-dihydro-1H-indol-2-
ones 9, but also 3-OH and 3-NO2 derivatives 11 and 10, respectively. Because many
biologically active compounds and natural products possess a 3-hydroxy-oxindole
framework with a tetrasubstituted stereogenic center C(3) [31][32], 3-NO2 derivatives
10 are interesting structures for further study. In addition, compounds 10 are potential
precursors for the synthesis of their 3-NH2 analogs.

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Helvetica Chimica Acta – Vol. 97 (2014)
A. K. and O. R. thank TBU in Zlꢀn for financial support (internal grants Nos. IGA/FT/2012/015 and
IGA/FT/2013/003, funded from the resources of specific university research). The authors are grateful to
ˇ
´
Mrs. H. Gerzova (Faculty of Technology, Tomas Bata University in Zlꢀn) for technical help.
Experimental Part
1. General. TLC: Alugramꢀ -SIL-G/UV254 foils (Macherey-Nagel); elution with benzene/AcOEt 4 :1,
CHCl3/EtOH 9 :1 and/or 19 :1, and CHCl3/AcOEt 7:3. Column chromatography (CC): silica gel (SiO2;
Merck, grade 60, 70 – 230 mesh); elution with CHCl3, then CHCl3/EtOH 99 :1 ! 8 :2 or benzene, and
then benzene/AcOEt 99 :1 ! 8 :2. M.p.: Kofler block or Gallencamp apparatus. IR Spectra: Smart
OMNI-Transmission Nicolet iS10 spectrophotometer; KBr; in cmꢀ1. NMR Spectra: Bruker Avance
spectrometer operating at 500.13 (1H), 125.76 (13C), and 50.68 MHz (15N), and Bruker Avance II 400
spectrometer operating at 400.13 (1H), 100.56 (13C), and 40.55 MHz (15N); in (D6)DMSO; d in ppm rel.
to TMS as an internal standard or to MeNO2 as an external standard in a co-axial capillary; J in Hz;
manufacturerꢄs software for all 2D experiments (gradient-selected gs-COSY, gs-NOESY, gs-HMQC, and
gs-HMBC). EI-MS (pos.): Shimadzu QP-2010 instrument within m/z 50 – 600 using direct inlet probe
(DI); analysis of samples in CH2Cl2 (30 mg/ml), 10 ml of the soln. evaporated in DI cuvette at 508; ion-
source temp., 2008; the energy of electrons, 70 eV; only signals exceeding rel. abundance of 5% are listed.
ESI-MS (pos.): amaZon X ion-trap mass spectrometer (Bruker Daltonics, DE-Bremen) equipped with
an ESI source; individual samples infused into the ion source as MeOH/H2O 1:1 (v/v) solns. via a syringe
pump at a constant flow rate of 4 ml/min; other instrumental conditions: m/z range 50 – 1500, electrospray
voltage, ꢀ 4.2 kV; drying gas temp., 2208; drying gas flow, 6.0 dm3/min, nebulizer pressure, 55.16 kPa,
cap. exit, 140 V; N2 used as nebulizing as well as drying gas. Elemental analysis (C, H, N): Flash EA 1112
elemental analyzer (Thermo Fisher Scientific).
Crystallography. Single crystals of 10h were prepared by liquid diffusion method [33] with AcOEt/
hexane as solvent/precipitant pair. The X-ray data were obtained at 150 K using Oxford Cryostream low-
temperature device on a Nonius KappaCCD diffractometer with MoKa radiation (l ¼ 0.71073 ꢅ), a
graphite monochromator, and the f and c scan mode. Data reductions were performed with DENZO-
SMN [34]. The absorption was corrected by integration methods [35]. Structures were solved by direct
methods (SIR92) [36] and refined by full matrix least-square based on F2 (SHELXL97) [37]. The H-
atoms were mostly localized on a difference Fourier map; however, to ensure uniformity of treatment of
crystal, all H-atoms were recalculated into idealized positions (riding model) and assigned temp. factors
Hiso(H) ¼ 1.2 Ueq(pivot atom) with CꢀH ¼ 0.93 ꢅ for H-atoms in aromatic rings. Rint ¼ S j F2o ꢀ Fo2;mean j /
SF2o, GOF ¼ [S(w(F2o ꢀ F2c )2)/(Ndiffrs ꢀ Nparams)]1/2 for all data, R(F) ¼ S jj Fo jꢀj Fc jj /S j Fo j for observed
data, wR(F2) ¼ [S(w(Fo2 ꢀ Fc2 )2)/(Sw(Fo2 )2)]1/2 for all data. All X-ray diffraction experiments, refinement,
and analysis of the obtained XRD data were carried out by A. R.
Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre,
No. CCDC-944756 for 10h. Copies of this information may be obtained free of charge from The Director,
CCDC, 12 Union Road, Cambridge CB21EY, UK (fax: þ 44-1223-336033; e-mail: deposit@ccdc.cam.
ac.uk or www: http://www.ccdc.cam.ac.uk).
2. General Procedure for the Preparation of 3-Aminoquinoline-2,4(1H,3H)-diones 5f and 5i.
Compounds were prepared by modifying the procedure described in [7]. The soln. of appropriate 3-
chloroquinoline-2,4(1H,3H)-dione (40 mmol) in DMF (120 ml) was added during 15 min to the stirred
and cooled (08) suspension of NH4Cl (4.27 g, 80 mmol) and K2CO3 (22.11 g, 160 mmol) in DMF (100 ml).
The mixture was stirred for 48 h and then poured onto crushed ice (800 ml). In the case of 5f, an oily
product was obtained, which was extracted with CHCl3 (3 ꢂ 30 ml), and the dried extract was separated
by CC (SiO2) to give 5f. In the case of 5i, the deposited precipitate was filtered with suction and
suspended in HCl (10%, 160 ml). After 2 h intensive stirring, the soluble portion was extracted with
benzene (3 ꢂ 15 ml), alkalized with aq. NH3, and the precipitate of 5i was filtered with suction and
crystallized from benzene. The insoluble portion was filtered off, collected with the evaporation residue
of benzene extract, and crystallized from AcOEt to give compound 5i.

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2.1. 3-Amino-3-benzyl-1-methylquinoline-2,4(1H,3H)-dione (5f). Prepared from 3-benzyl-3-chloro-
1-methylquinoline-2,4(1H,3H)-dione besides 2.36 g (21%) of 3-benzyl-3-hydroxy-1-methylquinoline-
2,4(1H,3H)-dione (1f). Yield: 3.584 g (32%). White solid. M.p. 101 – 1048 (benzene/hexane). IR: 3392,
3319, 3059, 3025, 2917, 1697, 1654, 1601, 1546, 1473, 1373, 1298, 1242, 1109, 1016, 943, 899, 852, 771, 735,
698, 663, 624, 582, 513. 1H- and 13C-NMR: see Table 3. EI-MS: 281 (8), 280 (43, Mþ), 190 (11), 189 (90),
162 (13), 161 (92), 133 (5), 118 (18), 116 (10), 106 (12), 105(5), 104 (10), 91 (11), 90 (7), 79 (6), 78 (9),
77 (23), 65 (20), 63 (6), 51 (10). ESI-MS (pos.): 561.2 (23, [2M þ H]þ), 303.2 (4, [M þ Na]þ ), 281.2 (100,
[M þ H]þ), 264.2 (4, [M þ H ꢀ NH3]þ). Anal. calc. for C17H16N2O2 (280.32): C 72.84, H 5.75, N 9.99;
found: C 72.86, H 5.75, N 9.63.
2.2. 3-Amino-3-benzyl-1-phenylquinoline-2,4(1H,3H)-dione (5i). Prepared from 3-benzyl-3-chloro-
1-phenylquinoline-2,4(1H,3H)-dione besides 4.94 g (36%) of 3-benzyl-3-hydroxy-1-phenylquinoline-
2,4(1H,3H)-dione (1i). Yield: 4.241 g (31%). White solid. M.p. 174 – 1788 (benzene). IR: 3394, 3321,
3062, 3027, 2925, 1708, 1673, 1598, 1494, 1463, 1344, 1300, 1288, 1245, 1209, 1136, 1105, 1072, 980, 933, 831,
798, 758, 712, 702, 667, 646, 592, 521, 501. 1H- and 13C-NMR: see Table 3. EI-MS: 343 (11), 342 (45, Mþ),
252 (16), 251 (94), 224 (17), 223 (100), 196 (18), 195 (13), 167 (24), 166 (8), 143 (9), 139 (6), 92 (9), 91
(56), 77 (24), 65 (7), 51 (13). ESI-MS (pos.): 685.2 (25, [2M þ H]þ), 343.2 (100, [M þ H]þ). Anal. calc.
for C22H18N2O2 (342.39) : C 77.17, H 5.30, N 8.18; found: C 77.06, H 5.31, N 7.96.
Table 3. 1H- and 13C-NMR Data ((D6)DMSO) of Compounds 5 and 7 (d in ppm)
Position
5f
5i
7e
7h
d(H)
d(C)
d(H)
d(C)
d(H)
d(C)
d(H)
d(C)
2
3
–
–
–
2.25
–
–
7.83
–
7.25
7.71
7.28
–
171.9
69.7
–
–
–
–
2.24
–
–
7.90
–
7.22
7.51
6.31
–
176.1
69.9
–
–
9.26
–
–
–
–
–
–
7.17
7.15
7.30
–
7.41
–
158.5
–
66.0
–
167.2
–
–
137.6
116.2
123.6
128.4
–
121.5
124.5
7.82
–
9.34
–
–
–
–
–
–
6.23
7.14
7.09
–
7.52
–
158.3
–
66.3
–
167.1
–
–
137.7
117.4
123.9
128.2
–
121.9
124.5
78.2
3a
3-NH2
4
4a
5
5a
6
7
8
8a
9
9a
9b
–
–
194.8
120.3
127.0
–
123.0
136.2
115.6
142.6
–
194.8
120.1
127.1
–
123.2
135.7
116.5
143.6
–
–
–
–
–
–
–
–
–
–
–
6.01
6.39
Substituent at N(1)
1
2,6
3.38
29.7
–
–
137.7
129.3
129.1
130.1
130.4
129.0
3.40
–
29.9
–
–
7.34
–
–
–
–
7.38
7.31
7.82
7.28
7.57
129.0
3,5
–
–
–
–
–
–
7.63
7.55
130.1
128.9
4
Substituent at C(3)
1
2
3,7
4,6
5
2.98
–
6.95
7.18
7.18
40.3
134.1
130.0
127.7
126.9
3.17
–
7.10
7.24
7.24
48.6
134.2
130.3
127.8
127.0
–
135.5
126.7
128.8
128.8
–
–
135.4
126.8
128.8
128.9
–
7.18
7.24
7.24
–
7.40
7.34
7.34
–

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Helvetica Chimica Acta – Vol. 97 (2014)
3. General Procedure for the Reduction of Compounds 5. NaBH4 (85 mg, 2.5 mmol) was added in
four portions during 5 min to the stirred soln. of compound 5 (2 mmol) in MeOH (10 ml). After 20 min,
crushed ice (up to 20 g), conc. HCl (0.25 ml), and H2O (4 ml) were added in successive steps under
cooling with crushed ice. The soln. was filtered, and the filtrate was alkalized with 6% NaHCO3.
Precipitated product was filtered off, washed with H2O, and recrystallized from an appropriate solvent.
The filtrate was extracted with CHCl3 (3 ꢂ 20 ml). The dried extract was evaporated to dryness, and the
residue was recrystallized from appropriate solvent. The yields are compiled in Table 1.
3.1. cis-3-Amino-3-butyl-3,4-dihydro-4-hydroxyquinolin-2(1H)-one (6a). Prepared from 5a. Yield:
351 mg (75%). White solid. M.p. 175 – 1778 (AcOEt). IR: 3365, 3073, 2958, 1681, 1596, 1565, 1486, 1390,
1307, 1251, 1201, 1072, 1033, 1004, 941, 840, 752, 698, 669, 520. 1H- and 13C-NMR: see Table 4. EI-MS: 234
(24, Mþ), 160 (5), 132 (15), 122 (28), 121 (6), 113 (58), 105 (9), 104 (8), 94 (12), 93 (13), 85 (27), 77 (18),
71 (10), 57 (21), 56 (100), 55 (9), 43 (44). ESI-MS (pos.): 491.3 (5, [2M þ Na]þ), 462.2 (4, [2M þ H]þ),
257.2 (4, [M þ Na]þ), 235.2 (100, [M þ H]þ ), 190.2 (15, [M þ H ꢀ NH3 ꢀ CO]þ). Anal. calc. for
C13H18N2O2 (234.29): C 66.64, H 7.74, N 11.96; found: C 66.42, H 7.72, N 11.86.
3.2. cis-3-Amino-3,4-dihydro-4-hydroxy-3-phenylquinolin-2(1H)-one (6b). Prepared from 5b. Yield:
406 mg (80%). White solid. M.p. 248 – 2548 (EtOH). IR: 3361, 3197, 3079, 2908, 1673, 1596, 1550, 1483,
1382, 1184, 1130, 1079, 1018, 975, 939, 817, 752, 694, 663, 568, 538. 1H- and 13C-NMR: see Table 4. EI-MS:
254 (24, Mþ), 133 (31), 122 (15), 106 (13), 105 (100), 104 (48), 94 (8), 93 (8), 77 (28), 51 (8). ESI-MS
(pos.): 277.2 (5, [M þ Na]þ), 255.2 (100, [M þ H]þ ), 238.2 (29, [M þ H ꢀ NH3]þ), 210.2 (9, [M þ H ꢀ
NH3 ꢀ CO]þ). Anal. calc. for C15H14N2O2 (254.28): C 70.85, H 5.55, N 11.02; found: C 70.70, H 5.47, N
10.79.
3.3. cis-3-Amino-3-benzyl-3,4-dihydro-4-hydroxyquinolin-2(1H)-one (6c). Prepared from 5c. Yield:
402 mg (75%). White solid. M.p. 184 – 1948 and then 234 – 2358 (AcOEt). IR: 3347, 3207, 3153, 3095,
2958, 2896, 2726, 1689, 1614, 1596, 1556, 1494, 1479, 1454, 1392, 1357, 1324, 1272, 1243, 1203, 1128, 1072,
1
1004, 935, 908, 755, 721, 700, 659, 592, 491. H- and 13C-NMR: see Table 4. EI-MS: 178 (11), 177 (100,
[M ꢀ Bn]þ), 176 (43), 175 (6), 160 (40), 159 (13), 149 (10), 147 (13), 132 (75), 131 (14), 122 (13), 120
(15), 119 (42), 118 (11), 117 (9), 105 (9), 104 (36), 94 (8), 93 (16), 92 (17), 91 (58), 77 (33), 65 (23), 51
(11). ESI-MS (pos.): 307.2 (4, [M þ K]þ), 291.2 (10, [M þ Na]þ), 269.2 (100, [M þ H]þ ). Anal. calc. for
C16H16N2O2 (268.31): C 71.62, H 6.01, N 10.44; found: C 71.73, H 6.04, N 10.39.
3.4. cis-3-Amino-3-butyl-3,4-dihydro-4-hydroxy-1-methylquinolin-2(1H)-one (6d). Prepared from
5d. Yield: 362 mg (73%). White solid. M.p. 117 – 1208 (benzene/hexane). IR: 3357, 3297, 2954, 2869, 1672,
1604, 1575, 1457, 1363, 1309, 1232, 1122, 1081, 1006, 950, 759, 673, 607. 1H- and 13C-NMR: see Table 4. EI-
MS: 248 (10, Mþ), 220 (11), 191 (12), 189 (9), 174 (14), 163 (9), 160 (7), 147 (7), 146 (31), 137 (11), 136
(100), 135 (19), 119 (8), 118 (51), 117 (8), 113 (69), 106 (20), 93 (8), 91 (22), 86 (13), 85 (20), 78 (7), 77
(20), 57 (11), 56 (88), 43 (34). ESI-MS (pos.): 491.3 (4, [2M þ Na]þ), 271.3 (4, [M þ Na]þ ), 249.3 (100,
[M þ H]þ ), 204.3 (11, [M þ H ꢀ NH3 ꢀ CO]þ). Anal. calc. for C14H20N2O2 (248.32): C 67.71, H 8.12, N
11.28; found: C 67.94, H 8.14, N 11.31.
3.5. cis-3-Amino-3,4-dihydro-4-hydroxy-1-methyl-3-phenylquinolin-2(1H)-one (6e). Prepared from
5e. Yield: 482 mg (90%). White solid. M.p. 199 – 2038 (benzene). IR: 3353, 3288, 3066, 2881, 2817, 1668,
1604, 1548, 1473, 1365, 1259, 1201, 1124, 1076, 1039, 987, 848, 757, 703, 684, 615, 568, 545. 1H- and
13C-NMR: see Table 4. EI-MS: 268 (30, Mþ), 136 (37), 135 (10), 134 (6), 133 (31), 118 (28), 106 (29), 105
(100), 104 (44), 91 (12), 77 (30), 51 (9). ESI-MS (pos.): 291.2 (5, [M þ Na]þ ), 269.3 (100, [M þ H]þ ),
252.2 (20, [M þ H ꢀ NH3]þ), 224.3 (8, [M þ H ꢀ NH3 ꢀ CO]þ). Anal. calc. for C16H16N2O2 (268.31): C
71.62, H 6.01, N 10.44; found: C 71.78, H 6.11, N 10.45.
3.6. cis-3-Amino-3-benzyl-3,4-dihydro-4-hydroxy-1-methylquinolin-2(1H)-one (6f). Prepared from
5f. Yield: 423 mg (75%). White solid. M.p. 137 – 1408 (AcOEt). IR: 3350, 3281, 3059, 3028, 2884, 2816,
2718, 1665, 1604, 1591, 1495, 1472, 1415, 1371, 1207, 1117, 1071, 1048, 971, 871, 761, 730, 701, 643, 587, 508.
1H- and 13C-NMR: see Table 4. EI-MS: 192 (12), 191 (100, [M ꢀ Bn]þ), 190 (33), 174 (70), 173 (9), 147
(15), 146 (83), 145 (13), 136 (13), 119 (24), 118 (36), 117 (14), 106 (15), 104 (23), 92 (11), 91 (72), 77
(25), 65 (22), 51 (10). ESI-MS (pos.): 321.2 (4, [M þ K]þ ), 305.2 (5, [M þ Na]þ ), 283.3 (100, [M þ H]þ ).
Anal. calc. for C17H18N2O2 (282.34): C 72.32, H 6.43, N 9.92; found: C 72.26, H 6.42, N 9.78.
3.7. cis-3-Amino-3-butyl-3,4-dihydro-4-hydroxy-1-phenylquinolin-2(1H)-one (6g). Prepared from 5g.
Yield: 428 mg (69%). White solid. M.p. 192 – 1958 (AcOEt). IR: 3376, 3342, 3288, 2954, 2929, 2859, 1674,

Helvetica Chimica Acta – Vol. 97 (2014)
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Helvetica Chimica Acta – Vol. 97 (2014)
1604, 1591, 1575, 1492, 1456, 1377, 1346, 1257, 1199, 1170, 1155, 1070, 1012, 989, 837, 756, 700, 646, 532, 501.
1H- and 13C-NMR: see Table 4. EI-MS: 310 (21, Mþ), 236 (6), 235 (7), 223 (6), 208 (12), 198 (21), 197
(64), 196 (21), 181 (14), 180 (61), 169 (7), 168 (31), 167 (17), 152 (6), 150 (7), 149 (69), 113 (54), 105
(10), 104 (11), 97 (14), 93 (15), 86 (33), 85 (27), 84 (9), 83 (14), 81 (9), 77 (25), 71 (20), 70 (12), 69 (24),
67 (12), 65 (13), 57 (54), 56 (100), 55 (31), 51 (12), 43 (65), 42 (25), 41 (52). ESI-MS (pos.): 621.3 (5,
[2M þ H]þ), 311.3 (100, [M þ H]þ ), 266.3 (7, [M þ H ꢀ NH3 ꢀ CO]þ). Anal. calc. for C19H22N2O2
(310.39): C 73.52, H 7.14, N 9.03; found: C 73.54, H 7.11, N 8.80.
3.8. cis-3-Amino-3,4-dihydro-1,3-diphenyl-4-hydroxyquinolin-2(1H)-one (6h). Prepared from 5h.
Yield: 515 mg (78%). White solid. M.p. 197 – 1998 (AcOEt). IR: 3357, 3303, 3224, 3058, 1685, 1589, 1493,
1459, 1446, 1349, 1297, 1261, 1197, 1122, 1072, 1035, 947, 893, 852, 762, 721, 698, 679, 650, 555, 509. 1H- and
13C-NMR: see Table 4. EI-MS: 331 (5), 330 (20, Mþ), 198 (13), 197 (53), 196 (18), 181 (9), 180 (41), 169
(6), 168 (28), 167 (12), 133 (26), 106 (32), 105 (100), 104 (51), 93 (8), 77 (32), 65 (6), 57 (6), 51 (13).
ESI-MS (pos.): 683.3 (7, [2M þ Na]þ), 661.2 (10, [2M þ H]þ), 369.2 (5, [M þ K]þ), 353.2 (10, [M þ Na]þ),
331.2 (100, [M þ H]þ ), 314.2 (31, [M þ H ꢀ NH3]þ), 286.2 (24, [M þ H ꢀ NH3 ꢀ CO]þ). Anal. calc. for
C21H18N2O2 (330.38): C 76.34, H 5.49, N 8.48; found: C 76.44, H 5.52, N 8.51.
3.9. cis-3-Amino-3-benzyl-3,4-dihydro-4-hydroxy-1-phenylquinolin-2(1H)-one (6i). Prepared from
5i. Yield: 550 mg (80%). White solid. M.p. 200 – 2018 (AcOEt). IR: 3355, 3278, 3060, 2917, 2724, 1676,
1585, 1489, 1454, 1358, 1346, 1292, 1255, 1201, 1128, 1072, 975, 955, 877, 856, 759, 729, 698, 640, 598, 503.
1H- and 13C-NMR: see Table 4. EI-MS: 254 (17), 253 (100, [M ꢀ Bn]þ), 252 (24), 236 (45), 235 (16), 208
(42), 197 (13), 196 (9), 180 (43), 168 (19), 167 (14), 120 (9), 119 (28), 118 (9), 104 (22), 92 (11), 91 (41),
77 (27), 65 (18), 51 (13). ESI-MS (pos.): 689.3 (11, [2M þ H]þ), 345.3 (100, [M þ H]þ). Anal. calc. for
C22H20N2O2 (344.41): C 76.72, H 5.85, N 8.13; found: C 76.83, H 5.90, N 8.13.
4. Reaction of Compounds 6 with Triphosgene. Triphosgene (¼ bis(trichloromethyl) carbonate;
43 mg, 0.145 mmol) was added in several portions during 1 h to the well-stirred soln. of 6 (0.4 mmol),
Et3N (0.121 ml, 0.87 mmol), and 4-(dimethylamino)pyridine (DMAP; 20 mg, 0.18 mmol) in benzene
(10 ml). The soln. was stirred at r.t. for 1 h, and the reaction was monitored by TLC. The suspension was
filtered, and the filtrate was evaporated to dryness. H2O (15 ml) was added to the residue, and the
suspension was extracted with benzene (3 ꢂ 20 ml). Collected extracts were dried, evaporated, and the
residue was crystallized from appropriate solvent or subjected to CC (SiO2).
4.1. 3,3a,5,9b-Tetrahydro-5-methyl-3a-phenyl[1,3]oxazolo[4,5-c]quinoline-2,4-dione (7e). Prepared
from 6e. Yield: 82 mg (70%). White solid. M.p. 267 – 2738 (EtOH). IR: 3232, 3123, 2971, 1754, 1690,
1614, 1584, 1492, 1465, 1448, 1395, 1346, 1304, 1265, 1209, 1191, 1160, 1131, 1092, 1021, 976, 949, 939, 896,
768, 722, 700, 679, 639, 581, 548. 1H- and 13C-NMR: see Table 3. EI-MS: 295 (19), 294 (100, Mþ), 266 (18),
250 (13), 221 (15), 207 (12), 206 (11), 205 (7), 194 (16), 165 (11), 163 (18), 152 (10), 147 (21), 146 (13),
135 (61), 134 (58), 118 (64), 117 (16), 107 (33), 106 (89), 105 (36), 104 (82), 103 (34), 91 (30), 90 (13), 89
(22), 78 (21), 77 (96), 76 (18), 65 (14), 63 (17), 51 (43). ESI-MS (pos.): 333.2 (27, [M þ K]þ), 317.2 (84,
[M þ Na]þ), 295.3 (51, [M þ H]þ), 251.3 (100, [M þ H ꢀ CO2]þ). Anal. calc. for C17H14N2O3 (294.30): C
69.38, H 4.79, N 9.52; found: C 69.43, H 4.91, N 9.37.
4.2. 3,3a,5,9b-Tetrahydro-3a,5-diphenyl[1,3]oxazolo[4,5-c]quinoline-2,4-dione (7h). Prepared from
6h. Yield: 92 mg (65%). White solid. M.p. 260 – 2708 (EtOH). IR: 3292, 3062, 2972, 1778, 1702, 1612,
1
1492, 1459, 1324, 1257, 1200, 1132, 1095, 1025, 948, 935, 896, 765, 752, 723, 696, 638, 596, 582. H- and
13C-NMR: see Table 3. EI-MS: 357 (22), 356 (89, Mþ), 328 (23), 285 (9), 284 (36), 283 (28), 256 (18), 208
(7), 207 (21), 205 (7), 197 (29), 196 (44), 181 (17), 180 (100), 179 (10), 168 (36), 152 (15), 127 (14), 104
(34), 103 (21), 89 (14), 77 (72), 63 (10), 51 (39). ESI-MS (pos.): 735.2 (5, [2M þ Na]þ), 395.2 (7, [M þ
K]þ), 379.3 (28, [M þ Na]þ), 357.3 (31, [M þ H]þ), 313.3 (100, [M þ H ꢀ CO2]þ). Anal. calc. for
C22H16N2O3 (356.37): C 74.15, H 4.53, N 7.86; found: C 74.22, H 4.75, N 7.76.
5. Rearrangement of Compounds 6. Method A. Under intensive stirring, compound 6 (0.75 mmol)
was dissolved in AcOH (4.5 ml). After cooling to 08, H2O (0.45 ml) and then solid NaNO2 (103 mg,
1.5 mmol) were added during 5 min, and stirring was continued for 2 h at r.t. Solid urea (45 mg,
0.75 mmol) was added to quench redundant HNO2, and after 15 min the mixture was blended with
crushed ice (15 g). The deposited precipitate was filtered with suction and washed with H2O (10 ml). The
filtrate was extracted with CHCl3 (3 ꢂ 20 ml). The extract was dried and evaporated in vacuo to dryness.
Both portions were collected and subjected to CC (SiO2). In the cases when the crude product was pasty,

Helvetica Chimica Acta – Vol. 97 (2014)
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the reaction mixture was extracted with CHCl3 (3 ꢂ 20 ml), the collected extracts were evaporated to
dryness and purified by CC (SiO2). Method B: The reaction was carried out in the same way as
Method A, merely the addition of urea was omitted. The yields are collected in Table 2.
5.1. 3-Butyl-1,3-dihydro-2H-indol-2-one (9a). Prepared from 6a. Yields: 34 (24%, Method A) and
33 mg (23%; Method B). White solid. M.p. 62 – 648 ([38]: 62 – 638 (hexane)). IR: 2956, 2931, 2867, 1705,
1618, 1469, 1411, 1376, 1340, 1317, 1228, 1172, 1153, 1101, 1020, 1002, 941, 929, 868, 831, 795, 748, 727, 704,
667, 580, 557, 492. 1H- and 13C-NMR: see Table 5. EI-MS: 189 (21, Mþ) , 146 (49), 133 (100), 132 (29), 128
(7), 119 (7), 118 (8), 117 (10), 105 (7), 104 (19), 91 (6), 90 (5), 78 (7), 77 (21), 51 (9). ESI-MS (pos.):
401.2 (8, [2M þ Na]þ), 379.3 (23, [2M þ H]þ), 228.1 (5, [M þ K]þ), 212.2 (19, [M þ Na]þ), 190.2 (100,
[M þ H]þ). Anal. calc. for C12H15NO (189.25): C 76.16, H 7.99, N 7.40; found: C 76.22, H 8.05, N 7.49.
5.2. 1,3-Dihydro-3-phenyl-2H-indol-2-one (9b). Prepared from 6b. Yields: 5 (3%; Method A) and
14 mg (9%; Method B). White solid. M.p. 190 – 1958 ([39]: 190 – 1928 (benzene/hexane)). IR: 3185, 3085,
3031, 1704, 1616, 1469, 1322, 1224, 1182, 1097, 1074, 1035, 939, 871, 836, 752, 709, 684, 663, 593. 1H- and
13C-NMR: see Table 5. EI-MS: 210 (14), 209 (87, Mþ), 181 (15), 180 (100), 179 (6), 165 (8), 152 (15), 96
(16), 90 (15), 89 (6), 77 (14), 76 (12), 63 (6), 51 (9). ESI-MS (pos.): 441.2 (14, [2M þ Na]þ), 438.2 (5,
[4M þ Ca]2þ), 419.2 (25, [2M þ H]þ), 333.7 (13, [3M þ Ca]2þ), 232.2 (17, [M þ Na]þ), 229.2 (8, [2M þ
Ca]2þ), 210.2 (100, [M þ H]þ), 132.2 (38, [M þ H ꢀ C6H6]þ). Anal. calc. for C14H11NO (209.24): C
80.36, H 5.30, N 6.69; found C 80.20, H 5.12, N 6.45.
5.3. 3-Benzyl-1,3-dihydro-2H-indol-2-one (9c). Prepared from 6c. Yields: 47 (28%; Method A) and
58 mg (35%; Method B). White solid. M.p. 129 – 1318 ([40]: 129 – 1308 (AcOEt/hexane)). IR: 3033, 2920,
2895, 2850, 1708, 1622, 1496, 1471, 1340, 1311, 1236, 1151, 1078, 1016, 962, 937, 854, 808, 748, 694, 665, 613,
588, 550. 1H- and 13C-NMR: see Table 5. EI-MS: 223 (19, Mþ), 132 (17), 104 (6), 92 (8), 91 (100), 77 (10),
65 (10), 51 (6). ESI-MS (pos.): 485.2 (6, [2M þ K]þ), 469.2 (12, [2M þ Na]þ), 466.2 (6, [4M þ Ca]2þ),
447.2 (5, [2M þ H]þ ), 354.7 (9, [3M þ Ca]2þ), 262.1 (6, [M þ K]þ), 246.2 (32, [M þ Na]þ), 243.2 (17,
[2M þ Ca]þ), 224.2 (100, [M þ H]þ), 196.2 (19, [M þ H ꢀ CO]þ). Anal. calc. for C15H13NO (223.27): C
80.69, H 5.87, N 6.27; found: C 80.25, H 5.95, N 6.52.
5.4. 3-Butyl-1,3-dihydro-1-methyl-2H-indol-2-one (9d). Prepared from 6d. Yields: 78 (51%;
Method A) and 64 mg (42%; Method B). Yellowish oil, b.p. 110 – 1208/0.5 Torr ([41]: 120 – 1228/
0.6 Torr). IR: 3055, 2956, 2931, 1712, 1614, 1494, 1469, 1376, 1346, 1259, 1130, 1085, 1020, 925, 750,
1
701, 611, 541. H- and 13C-NMR: see Table 5. EI-MS: 203 (58, Mþ), 202 (54), 174 (11), 161 (16), 160
(100), 148 (10), 147 (50), 132 (15), 131 (11), 130 19), 104 (8). ESI-MS (pos.): 429.3 (19, [2M þ Na]þ),
426.3 (7, [4M þ Ca]2þ), 407.3 (5, [2M þ H]þ), 242.2 (13, [M þ K]þ), 226.2 (44, [M þ Na]þ), 204.2 (100,
[M þ H]þ ). Anal. calc. for C13H17NO (203.28): C 76.81, H 8.43, N 6.89; found: C 76.65, H 8.41, N 6.79.
5.5. 1,3-Dihydro-1-methyl-3-phenyl-2H-indol-2-one (9e). Prepared from 6e. Yields: 8 (5%; Meth-
od A) and 18 mg (11%; Method B). White solid. M.p. 117 – 1208 ([42]: 117 – 1198 (cyclohexane)). IR:
3052, 3023, 2933, 2908, 1693, 1610, 1496, 1465, 1374, 1346, 1263, 1170, 1124, 1085, 1020, 931, 877, 752, 730,
703, 642, 543. 1H- and 13C-NMR: see Table 5. EI-MS: 224 (18), 223 (100, Mþ), 195 (13), 194 (73), 180 (6),
179 (10), 167 (11), 165 (15), 153 (7), 152 (12), 150 (7), 149 (52), 139 (8), 127 (11), 125 (11), 118 (13), 113
(14), 111 (19), 109 (9), 99 (13), 97 (26), 95 (13), 85 (31), 84 (10), 83 (32), 82 (13), 81 (16), 77 (11), 76
(11), 71 (53), 70 (20), 69 (32), 57 (69), 56 (14), 55 (33), 43 (51). ESI-MS (pos.): 469.2 (36, [2M þ Na]þ),
447.2 (5, [2M þ H]þ), 354.7 (9, [3M þ Ca]2þ), 262.1 (36, [M þ K]þ), 246.2 (100, [M þ Na]þ), 243.2 (30,
[2M þ Ca]þ), 224.2 (78, [M þ H]þ). Anal. calc. for C15H13NO (223.27): C 80.69, H 5.87, N 6.27; found: C
80.27, H 5.82, N 6.14.
5.6. 3-Benzyl-1,3-dihydro-1-methyl-2H-indol-2-one (9f). Prepared from 6f. Yields: 71 (40%;
Method A) and 50 mg (28%; Method B). White solid. M.p. 65 – 688 ([43]: 67 – 688 (hexane)). IR: 3055,
3027, 2917, 1700, 1610, 1492, 1469, 1454, 1371, 1355, 1338, 1265, 1232, 1157, 1120, 1087, 991, 894, 850, 792,
755, 750, 725, 703, 622, 584, 539. 1H- and 13C-NMR: see Table 5. EI-MS: 238 (7), 237 (39, Mþ), 160 (8),
147 (8), 146 (75), 118 (8), 117 (7), 92 (8), 91 (100), 77 (5), 65 (13). ESI-MS (pos.): 497.2 (26, [2M þ
Na]þ), 494.3 (9, [4M þ Ca]2þ), 375.8 (18, [3M þ Ca]2þ), 276.2 (13, [M þ K]þ), 260.2 (82, [M þ Na]þ),
257.2 (35, [2M þ Ca]þ), 238.3 (100, [M þ H]þ), 210.3 (5, [M þ H ꢀ CO]þ). Anal. calc. for C16H15NO
(237.30): C 80.98, H 6.37, N 5.90; found: C 80.68, H 6.34, N 5.84.
5.7. 3-Butyl-1,3-dihydro-1-phenyl-2H-indol-2-one (9g). Prepared from 6g. Yields: 91 (46%; Meth-
od A) and 78 mg (39%; Method B). Yellowish oil. B.p. 165 – 1858/0.5 Torr ([30]: 170 – 1908/0.5 Torr). IR:

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2956, 2929, 2857, 1720, 1612, 1502, 1481, 1463, 1373, 1326, 1220, 1170, 1101, 1025, 752, 700, 644, 626, 590,
566. 1H- and 13C-NMR: see Table 5. EI-MS: 266 (9), 265 (44, Mþ), 223 (12), 222 (67, 210 (16), 209 (100),
196 (14), 181 (8), 180 (47), 167 (12), 152 (12), 115 8), 91 (14), 77 (28), 51 (19). ESI-MS (pos.): 553.3 (6,
[2M þ Na]þ), 531.2 (6, [2M þ H]þ), 304.2 (7, [M þ K]þ), 288.3 (19, [M þ Na]þ), 266.3 (100, [M þ H]þ).
Anal. calc. for C18H19NO (265.35): C 81.47, H 7.22, N 5.28; found: C 81.21, H 7.13, N 5.13.
5.8. 1,3-Dihydro-1,3-diphenyl-2H-indol-2-one (9h). Prepared according to [30]. White solid. M.p.
110 – 1128 ([30]: 111 – 1138 (hexane)). IR: 3068, 3028, 2998, 1713, 1610, 1594, 1501, 1467, 1454, 1366, 1325,
1298, 1251, 1215, 1178, 1168, 1099, 1074, 1026, 980, 883, 868, 795, 756, 739, 697, 659, 638, 619, 601, 505. 1H-
and 13C-NMR: see Table 5. EI-MS: 286 (13), 285 (59, Mþ), 257 (21), 256 (100), 254 (16), 180 (13), 152
(8), 128 (7), 127 (13), 77 (10), 51 (8). ESI-MS (pos.): 593.2 (14, [2M þ Na]þ), 571.2 (4, [2M þ H]þ), 324.2
(20, [M þ K]þ), 308.2 (58, [M þ Na]þ), 286.2 (100, [M þ H]þ). Anal. calc. for C20H15NO (285.34): C
84.19, H 5.30, N 4.91; found: C 84.29, H 5.30, N 4.76.
5.9. 3-Benzyl-1,3-dihydro-1-phenyl-2H-indol-2-one (9i). Prepared from 6i. Yields: 52 (23%;
Method A) and 58 mg (26%; Method B). White solid. M.p. 90 – 948 ([30]: 90 – 948 (i-PrOH)). IR:
3060, 3035, 2917, 2865, 1722, 1608, 1592, 1496, 1479, 1463, 1452, 1371, 1327, 1275, 1225, 1171, 1101, 1078,
1024, 914, 845, 752, 733, 700, 645, 633, 594, 561. 1H- and 13C-NMR: see Table 5. EI-MS: 300 (13), 299 (54,
Mþ), 222 (10), 209 (13), 208 (81), 181 (7), 180 (49), 179 (12), 178 (8), 152 (19), 92 (8), 91 (100), 77 (22),
65 (13), 51 (19). ESI-MS (pos.): 621.2 (11, [2M þ Na]þ), 599.2 (7, [2M þ H]þ), 338.2 (10, [M þ K]þ),
322.2 (24, [M þ Na]þ), 300.2 (100, [M þ H]þ). Anal. calc. for C21H17NO (299.37): C 84.25, H 5.72, N 4.68;
found: C 84.02, H 5.71, N 4.50.
5.10. 1,3-Dihydro-3-nitro-3-phenyl-2H-indol-2-one (10b). Prepared from 6b. Yields: 59 (31%;
Method A) and 13 mg (7%; Method B). Yellowish solid. M.p 140 – 1428 (benzene/hexane). IR: 3208,
3178, 3108, 1727, 1617, 1552, 1471, 1448, 1411, 1340, 1328, 1295, 1218, 1101, 1083, 1002, 948, 821, 748, 698,
674, 644, 620, 611, 485. 1H- and 13C-NMR: see Table 6. EI-MS: 210 (14), 209 (93), 208 (32), 181 (17), 180
(100), 179 (11), 178 (6), 152 (17), 90 (17), 89 (7), 77 (12), 76 (12), 63 (5), 51 (6). ESI-MS (pos.): 531.1 (5,
[2M þ Na]þ), 293.1 (20, [M þ K]þ), 277.2 (16, [M þ Na]þ), 247.1 (17, [M þ K ꢀ NO2]þ), 231.2 (24, [M þ
Na ꢀ NO2]þ), 208.2 (100, [M þ H ꢀ NO2]þ), 180.2 (8, [M þ H ꢀ NO2 ꢀ CO]þ). Anal calc. for C14H10N2O3
(254.24): C 66.14, H 3.96, N 11.02; found: C 66.08, H 3.80, N 10.93.
5.11. 3,4-Dihydro-1-methyl-3-nitro-3-phenylquinolin-2(1H)-one (10e). Prepared from 6e. Yields: 56
(28%; Method A) and 24 mg (12%; Method B). Yellow solid, m.p. 123 – 1288 (cyclohexane). IR: 3060,
2975, 2937, 1727, 1610, 1558, 1492, 1469, 1336, 1245, 1128, 1089, 952, 806, 752, 738, 696, 684, 538. 1H- and
13C-NMR: see Table 6. EI-MS: 224 (15), 223 (100), 222 (68), 208 (8), 207 (14), 195 (11), 194 (69), 193
(11), 179 (10), 178 (6), 166 (7), 165 (26), 153 (6), 152 (17), 151 (8), 118 (12), 116 (7), 89 (8), 76 (7). ESI-
MS (pos.): 559.2 (5, [2M þ Na]þ), 307.1 (45, [M þ K]þ), 291.2 (62, [M þ Na]þ), 261.1 (37, [M þ K ꢀ
NO2]þ), 245.2 (98, [M þ Na ꢀ NO2]þ), 222.2 (100, [M þ H ꢀ NO2]þ), 194.2 (4, [M þ H ꢀ NO2 ꢀ
CO]þ). Anal. calc. for C15H12N2O3 (268.27): C 67.16, H 4.51, N 10.44; found: C 66.99, H 4.47, N 10.45.
5.12. 1,3-Dihydro-3-nitro-1,3-diphenyl-2H-indol-2-one (10h). Prepared from 6b. Yields: 10 (4%;
Method A) and 40 mg (16%; Method B). Yellowish solid, M.p. 133 – 1388 (benzene/hexane). IR: 3066,
3043, 2924, 1739, 1610, 1594, 1556, 1498, 1465, 1446, 1371, 1340, 1324, 1309, 1213, 1180, 1099, 1076, 1025,
962, 948, 835, 808, 757, 732, 694, 651, 622, 588. 1H- and 13C-NMR: see Table 6. EI-MS: 286 (11), 285 (50),
284 (8), 257 (21), 256 (100), 254 (20), 180 (16), 179 (6), 178 (6), 152 (11), 151 (6), 128 (8), 127 (15), 51
(9), 44 (7). ESI-MS (pos.): 683.1 (3, [2M þ Na]þ), 369.1 (16, [M þ K]þ), 353.2 (24, [M þ Na]þ), 323.2
(30, [M þ K ꢀ NO2]þ), 307.2 (66, [M þ Na ꢀ NO2]þ), 285.2 (100, [M þ H ꢀ NO2]þ). Anal. calc. for
C20H14N2O3 (330.34): C 72.72, H 4.27, N 8.48; found: C 72.29, H 4.26, N 8.26.
¯
Crystallographic Data for 10h. C20H14N2O3, Mr 330.33, triclinic, P1, a ¼ 8.7901(5), b ¼ 9.5950(4), c ¼
9.9790(3) ꢅ, a ¼ 91.935(4), b ¼ 101.309(6), g ¼ 106.188(5)8, Z ¼ 2, V¼ 789.07(7) ꢅ3, Dc ¼ 1.390 g cmꢀ3
,
m ¼ 0.095 mmꢀ1, Tmin/Tmax ¼ 0.973/0.982; ꢀ 11 ꢃ h ꢃ 11, ꢀ 12 ꢃ k ꢃ 12, ꢀ 12 ꢃ l ꢃ 12; 14684 reflections
measured (qmax ¼ 27.58), 14644 independent (Rint ¼ 0.0229), 3073 with I > 2s(I), 226 parameters, S ¼
1.077, R1 (obs. data) ¼ 0.0388, wR2 (all data) ¼ 0.0971; max., min. residual electron density ¼ 0.303, ꢀ
0.227 eꢅꢀ3
.
5.13. 1,3-Dihydro-3-hydroxy-3-phenyl-2H-indol-2-one (11b). Prepared from 6b. Yield: 14 mg (8%,
Method B). White solid. M.p. 211 – 2168 ([44]: 211 – 2148 (benzene)). IR: 3415, 3214, 3072, 1708, 1617,
1
1469, 1340, 1303, 1184, 1120, 1066, 939, 900, 781, 755, 738, 690, 665, 609, 497. H- and 13C-NMR: see

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Table 6. 1H-, 13C-, and 15N-NMR Data ((D6)DMSO) of Rearrangement Products of 6: Compounds 10,
11, and 12 (d in ppm)
Position 10b
d(H)
10e
10h
11b
11h
12h
d(C)
d(H) d(C) d(H) d(C) d(H) d(C) d(H) d(C) d(H) d(C)
1
2
3
–
–
–
–
246.0a)
168.8
94.9
–
–
–
–
–
167.4
94.4
–
–
–
–
–
–
–
166.9
94.6
–
–
–
–
6.67
–
–
–
–
–
6.99
–
–
176.4
77.2
–
133.1
125.1 7.57
123.5 8.06
–
–
–
7.33
–
–
178.6
77.4
–
176.0
76.8
–
133.5
126.0
119.2
148.4
103.9
144.3
3-OH
3a
4
5
6
–
–
124.9
126.1
123.2
132.4
111.4
143.0
–
123.4
123.2
133.8
7.63
7.24
7.55
7.11
–
7.69
7.32
7.66
7.33
–
125.9 7.81 126.5
123.8 7.38 124.4
132.5 7.59 132.6
110.6 6.97 110.9
7.15 124.9 7.30
7.01 122.1 7.16
7.29 129.3 7.35
6.95 109.9 6.68
129.5
109.4 7.47
–
7
7a
144.3
–
144.2
–
142.0
–
143.2
134.3
126.8 7.59
129.8 7.68
128.3 7.59
–
Substituent at N(1)
1
2, 6
3, 5
4
11.38b)
–
–
–
–
–
–
–
3.30
27.0
–
133.0 10.45
–
–
–
–
–
–
139.9
126.8
130.2
129.0
–
–
–
–
–
–
7.55 126.9
7.66 130.1
–
–
–
7.51
7.64
7.53
c
)
129.2
Substituent at C(3)
1
2
3, 7
4, 6
–
131.8
129.0
128.3
130.2
–
131.6
129.0
128.4
130.3
–
131.6
129.1
128.4
130.5
–
141.6
–
141.3
–
139.9
125.5
128.7
128.3
c
7.53
7.51
7.55
7.52
7.52
7.55
)
)
)
7.33 125.5 7.43
7.36 128.2 7.44
7.31 127.5 7.35
125.5 7.53
128.4 7.50
127.8 7.50
c
c
b
a) d(15N). ) 1J(15N,1H) ¼ 95.1 Hz. c) 7.57 – 7.64.
Table 6. EI-MS: 225 (38, Mþ), 198 (8), 197 (61), 196 (100, [M ꢀ 29]þ), 180 (13), 167 (8), 120 (29), 105
(15), 98 (12), 92 (18), 77 (31), 76 (11), 65 (12), 51 (12), identical to that of (R)-11b [45]. ESI-MS (pos.):
489.1 (5, [2M þ K]þ), 473.1 (43, [2M þ Na]þ), 470.2 (10, [4M þ Ca]2þ), 357.7 (64, [3M þ Ca]2þ), 264.1 (53,
[M þ K]þ), 248.2 (100, [M þ Na]þ), 208.2 (98, [M þ H ꢀ H2O]þ), 180.2 (10, [M þ H ꢀ H2O ꢀ CO]þ).
Anal. calc. for C14H11NO2 (225.24): C 74.65, H 4.92, N 6.22; found C 74.50, H 4.97, N 5.95.
5.14. 1,3-Dihydro-3-hydroxy-1,3-diphenyl-2H-indol-2-one (11h). Prepared from 6h. Yields: 29 (13%;
Method A) and 20 mg (9%; Method B). Colorless solid. M.p. 170 – 1758 ([46]: 172 – 1738 (benzene/
cyclohexane)). IR: 3419, 3027, 1708, 1612, 1594, 1498, 1465, 1454, 1374, 1355, 1282, 1172, 1112, 1068, 1025,
989, 927, 902, 827, 779, 755, 725, 700, 647, 611, 576, 489 cmꢀ1. 1H- and 13C-NMR: see Table 6. EI-MS: 302
(7), 301 (31, Mþ), 274 (6), 273 (35), 272 (100), 256 (8), 196 (9), 191 (13), 167 (18), 166 (6), 105 (17), 77
(43), 57 (26), 51 (15). ESI-MS (pos.): 625.1 (22, [2M þ Na]þ), 471.7 (14, [3M þ Ca]2þ), 340.2 (12, [M þ
K]þ), 324.2 (33, [M þ Na]þ), 302.2 (5, [M þ H]þ), 284.2 (100, [M þ H ꢀ H2O]þ). Anal. calc. for
C20H15NO2 (301.34): C 79.72, H 5.02, N 4.65; found: C 79.59, H 4.94), N 4.63.
5.15. 1,3-Dihydro-3-hydroxy-6-nitro-1,3-diphenyl-2H-indol-2-one (12h). Prepared from 6h. Yields: 8
(3%; Method A) and 21 mg (8%; Method B). Colorless solid. M.p. 301 – 3058 (AcOEt). IR: 3335, 3092,
1705, 1609, 1527, 1453, 1434, 1376, 1345, 1260, 1210, 1177, 1119, 1060, 1032, 958, 918, 870, 858, 837, 779, 731,
714, 697, 656, 643, 505. EI-MS: 347 (7), 346 (31, Mþ), 319 (7), 318 (37), 317 (57), 301 (11), 285 (12), 273
(7), 272 (20), 271 (17), 256 (21), 167 (10), 166 (6), 135 (11), 105 (37), 77 (49), 51 (11), 45 (13), 44 (100).
ESI-MS (pos.): 385.1 (10, [M þ K]þ), 369.2 (100, [M þ Na]þ), 347.2 (25, [M þ H]þ), 329.2 (75, [M þ H ꢀ
H2O]þ). Anal. calc. for C20H14N2O4 (346.34): C 69.36, H 4.07, N 8.09; found: C 69.45, H 4.19, N 7.94.
5.16. 1,1’,3,3’-Tetrahydro-3,3’-diphenyl-2H,2’H-3,3’-biindole-2,2’-dione (13b). Prepared from 6b.
Yield: 12.5 mg (4%; Method A). White solid. M.p. 187 – 2068 ([47]: 188 – 1928, [28]: 234 – 2368

Helvetica Chimica Acta – Vol. 97 (2014)
611
(AcOEt/hexane). IR: 3416, 3203, 3057, 1705, 1673, 1618, 1595, 1472, 1448, 1374, 1326, 1296, 1239, 1201,
1104, 1067, 1026, 1002, 926, 873, 846, 758, 750, 696, 658, 608, 589, 570, 537. ESI-MS (pos.): 455.1 (12, [M þ
K]þ), 439.2 (37, [M þ Na]þ), 417.2 (100, [M þ H]þ), 208.2 (100, [M þ H ꢀ 209]þ). Anal. calc. for
C28H20N2O2 (416.67): C 80.75, H 4.84, N 6.73; found C 80.50, H 4.97, N 6.95.
5.17. 1,1’,3,3’-Tetrahydro-1,1’-dimethyl-3,3’-diphenyl-2H,2’H-3,3’-biindole-2,2’-dione (13e). Prepared
from 6e. Yields: 7 (2%; Method A) and 7 mg (2%; Method B). White solid. M.p. 212 – 2208 ([28]: 215 –
2178 (benzene/cyclohexane)). IR: 3048, 2962, 2929, 2881, 1708, 1608, 1492, 1471, 1373, 1347, 1259, 1133,
1081, 1027, 973, 757, 736, 701, 646, 603, 541, 526. EI-MS: 223 (81), 222 (100), 208 (8), 207 (26), 195 (12),
194 (68), 193 (16), 192 (9), 181 (11), 179 (11), 166 (11), 165 (37), 153 (11), 152 (26), 151 (13), 127 (11),
126 (10), 118 (9), 116 (12), 113 (10), 111 (24), 99 (12), 98 (9), 97 (22), 96 (10), 95 (8), 91 (12), 89 (11), 85
(23), 84 (12), 83 (24), 82 (14), 77 (12), 76 (14), 71 (39), 70 (16), 69 (24), 57 (46), 55 (20), 43 (40), 41 (15).
ESI-MS (pos.): 911.3 (26, [2M þ H]þ), 483.2 (4, [M þ K]þ), 467.2 (100, [M þ Na]þ), 445.3 (7, [M þ H]þ).
Anal. calc. for C30H24N2O2 (444.52): C 81.06, H 5.44, N 6.30; found: C 80.98, H 5.43, N 6.21.
5.18. 1,1’,3,3’-Tetrahydro-1,1’,3,3’-tetraphenyl-2H,2’H-3,3’-biindole-2,2’-dione (13h). Prepared from
6h. Yields: 26 (6%; Method A) and 13 mg (3%; Method B). White solid. M.p. 220 – 2238(EtOH). IR:
3059, 2922, 1720, 1607, 1589, 1498, 1464, 1372, 1324, 1297, 1239, 1203, 1179, 1105, 1073, 1033, 1011, 912,
879, 758, 732, 698, 654, 633, 612, 597, 521. EI-MS: 286 (10), 285 (50), 284 (36), 257 (21), 256 (100), 255
(10), 254 (35), 181 (7), 180 (14), 179 (8), 178 (10), 152 (16), 151 (11), 128 (9), 127 (23), 126 (10), 77 (23),
51 (23). ESI-MS (pos.): 607.2 (8, [M þ K]þ), 591.2 (16, [M þ Na]þ), 569.2 (55, [M þ H]þ), 324.2 (12,
[M þ K ꢀ 283]þ), 308.2 (33, [M þ Na ꢀ 283]þ), 286.3 (100, [M þ H ꢀ 283]þ). Anal. calc. for C40H28N2O2
(568.66): C 84.48, H 4.96, N 5.63; found: C 84.68, H 5.06, N 5.63.
6. Transformations of Compounds 9 and 10. 6.1. Reaction of 9h with HNO2. Method C. The reaction
was carried out in the same way as described for Method A, merely the charge of NaNO2 was doubled,
and the reaction time was prolonged to 3 h. CC (SiO2) of the crude reaction product provided
compounds 9h (66 mg, 31%), 10h (37 mg, 15%), 12h (16 mg, 6%) and 13h (30 mg, 7%).
6.2. Reaction of 9h with NaNO2 and HNO3. Method D. The reaction was carried out in the same way
as described for Method A, merely the addition of H2O was omitted, conc. HNO3 (0.2 ml) was added, and
the reaction time was prolonged to 3 h. CC (SiO2) of the crude reaction product furnished compounds
10h (37 mg, 15%), 11h (59 mg, 26%), and 12h (41 mg, 16%).
6.3. Reaction of 10h with Urea. The soln. of 10h (42 mg, 0.126 mmol) and urea (11 mg, 0.18 mmol) in
AcOH (2 ml) and H2O (0.1 ml) was heated to 508 for 3 h. The reaction mixture was diluted with H2O and
extracted with CHCl3. After evaporation, the residue was purified by CC (SiO2), to yield 10h (19 mg,
62%), 11h (7 mg, 24%) and 9h (0.3 mg, 1%).
REFERENCES
ˇ
´
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Received August 16, 2013