The first example of the synthesis of 1-aminoindole derivatives by the Nenitzescu reaction

Article abstract of DOI:10.1007/s11172-005-0198-3

The Nenitzescu reaction with 1-methyl-2-nitrovinylhydrazine was studied for the first time. 1-Amino-6-hydroxyindole derivatives containing a nitro group in position 3 were synthesized.

Full text of DOI:10.1007/s11172-005-0198-3

2834
Russian Chemical Bulletin, International Edition, Vol. 53, No. 12, pp. 2834—2839, December, 2004
The first example of the synthesis of 1ꢀaminoindole derivatives
by the Nenitzescu reaction
V. M. Lyubchanskaya,a S. A. Savina,a L. M. Alekseeva,a A. S. Shashkov,b V. V. Chernyshev,c and V. G. Granika
ꢀ
aState Scientific Center of Antibiotics (SSCA),
3a ul. Nagatinskaya, 117105 Moscow, Russian Federation.
Fax: +7 (095) 231 4284. Eꢀmail: vggranik@mail.ru
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328
cDepartment of Chemistry, M. V. Lomonosov Moscow State University,
Leninskie Gory, 119899 Moscow, Russian Federation.
Fax: +7 (095) 939 3654. Eꢀmail: cher@biocryst.phys.msu.su
The Nenitzescu reaction with 1ꢀmethylꢀ2ꢀnitrovinylhydrazine was studied for the first
time. 1ꢀAminoꢀ6ꢀhydroxyindole derivatives containing a nitro group in position 3 were syntheꢀ
sized.
Key words: nitro enehydrazines, Nenitzescu reaction, 1ꢀaminoindoles, Xꢀray diffraction
analysis.
1ꢀAminoindoles attract considerable attention of the
researchers because some of them are biologically active,1
exhibiting, e.g., psychotropic,2 antispasmodic,3 and analꢀ
gesic effects.4 1ꢀAminoindole derivatives have been exꢀ
tensively studied as potential therapeutic agents for treatꢀ
ment of Alzheimer's disease.5 An
1ꢀarylaminoindole derivative has
been clinically approved and
recommended as a symptomatic
means.5
indole and 5ꢀhydroxybenzofuran derivatives, allows a wide
variation in the structures of the starting quinones and
enamines.12—14 Use of nontrivial starting reagents often
leads to uncommon products.15,16 We carried out the
Nenitzescu reaction with an Nꢀamino derivative of nitro
enamine, namely, 1ꢀmethylꢀ2ꢀnitrovinylhydrazine (2)
prepared by transamination of 2ꢀdimethylaminoꢀ1ꢀnitroꢀ
propꢀ1ꢀene (1)17 with hydrazine hydrate. Note that
enehydrazines have not been used hitherto as enamine
components in the Nenitzescu reaction. With hydrazine 2
as the starting reagent, one could obtain 1ꢀaminoindole
derivatives bearing such a strong electronꢀwithdrawing
substituent in position 3 as the nitro group. As noted
above, the synthesis of such compounds by conventional
methods is quite problematic.
At present, there are a numꢀ
ber of routes to 1ꢀaminoindole
derivatives; however, the most commonly used method
for the synthesis of compounds of this type and primarily
unsubstituted 1ꢀaminoindole is direct amination of inꢀ
doles with hydroxylamineꢀOꢀsulfonic acid6 or, less often,
Oꢀ(diphenylphosphinyl)hydroxylamine proposed later as
an aminating agent.7 A rather serious limitation of this
method is its applicability only to indoles containing no
strong electronꢀwithdrawing substituents. Among other
techniques, reduction of 1ꢀnitrosoindoles to 1ꢀaminoꢀ
indoles8,9 is worth noting. A number of investigations was
devoted to contraction of the pyridazine ring in cinnoline
derivatives.1,10
In the present study, 1ꢀaminoindole derivatives were
synthesized by the Nenitzescu reaction (Scheme 1); this
approach has been recently published by us in a brief
communication.11 The Nenitzescu reaction, which is the
most accessible method for the synthesis of 5ꢀhydroxyꢀ
We assumed that the presence of such a substituent as
the amino group in enamine could complicate condensaꢀ
tion of the enamine component with quinone.
Indeed, the condensation of enamine 2 with pꢀbenzoꢀ
quinone follows a different pathway: the Michael C—C
addition indispensable for the Nenitzescu reaction does
not occur in this case, compound 2 behaving like a hydrꢀ
azine derivative rather than an enamine. The reaction
gave the corresponding hydrazone, namely, 4ꢀ[(1ꢀmeꢀ
thylꢀ2ꢀnitrovinyl)hydrazono]cyclohexaꢀ2,5ꢀdienone (3)
(see Scheme 1). For this reason, we synthesized Nꢀbenꢀ
zylideneꢀN´ꢀ(1ꢀmethylꢀ2ꢀnitrovinyl)hydrazine (4) conꢀ
taining no primary amino group by condensation of comꢀ
pound 2 with benzaldehyde. The Nenitzescu reaction of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2719—2724, December, 2004.
1066ꢀ5285/04/5312ꢀ2834 © 2004 Springer Science+Business Media, Inc.

1ꢀAminoindole derivatives
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2835
Scheme 1
Reagents and conditions: i. NH2NH2•H2O, 20 °C, 1 h; ii. pꢀBenzoquinone, 20 °C, 2 h; iii. Benzaldehyde, 20 °C, 1 h; iv. pꢀBenzoꢀ
quinone, TsOH, 20 °C, 3 h; v. Ac2O, refluxing, 1 h; vi. Ac2O, H2SO4 (one drop), 20 °C, 1.5 h; vii. HCl, EtOH, H2O, refluxing,
30 min; viii. Piperidine, benzene, EtOH, refluxing, 6 h; ix. HCl, BunOH, H2O, refluxing, 45 min.
Scheme 2
compound 4 with pꢀbenzoquinone yielded indole 5.
The indole structure of compound 5 was confirmed by
1H NMR data; however, the position of the hydroxy group
(5 or 6) requires special evidence since nitro enamines in
the Nenitzescu reaction are known to give 6ꢀhydroxyꢀ
indoles.18 A probable reaction mechanism and reasons
for the formation of 6ꢀhydroxy derivatives in the reactions
of quinones with nitro enamines were analyzed in detail
earlier.13,14,18 An initial attack of the Cβ atom of nitro
enamines on the C(1) atom of the quinone is shown in
Scheme 2.
tion peaks of the signal at δ 117.3 (C(3a)) with the signals
at δ 7.20 (dd, H(5), J1 = 8.6 Hz, J2 = 1.2 Hz) and 7.59 (d,
H(7), J2 = 1.2 Hz), which unambiguously indicates the
formation of 6ꢀhydroxy (5) and then 6ꢀacetoxy derivaꢀ
tives (6). In a structure containing the 5ꢀacetoxy group,
Being insufficiently soluble for HMBC NMR study,
compound 5 was Oꢀacetylated in boiling acetic anhydride
to give derivative 6. Its HMBC spectrum shows correlaꢀ

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Lyubchanskaya et al.
the signal for C(3a) would show only one correlation peak
with the signal for H(7) (for complete spectroscopic data,
see Experimental).
A similar shift was observed when acyclic intermediꢀ
ates (hydroquinone adducts) were converted into final
Nenitzescu products (e.g., indoles).20 The 1H and
13C chemical shifts of the signal for the benzylidene proꢀ
ton also differ largely: δ 9.14 and 166.6 for compound 6
and δ 7.88, 8.06 and 79.1, 83.1 for compound 7, respecꢀ
tively. 6ꢀAcetoxyꢀ1ꢀacetylaminoꢀ2ꢀmethylꢀ3ꢀnitroindole
(8) was obtained as a byꢀproduct.
Acid hydrolysis of compound 7 unexpectedly gave
1ꢀacetylaminoꢀ6ꢀhydroxyꢀ2ꢀmethylꢀ3ꢀnitroindole (9) in
high yield; in addition, a small amount of indole 5 was
isolated.
The hydrolysis aimed at the azomethine fragment and
the acetoxy groups in compound 7 is accompanied by
migration of the acyl residue (acylotropic rearrangement).
Such rearrangements were reported earlier.21,22 Apparꢀ
ently, the same scheme is valid in the formation of indole
8 from compound 7 (rather than from compound 5 as we
assumed earlier11). This is evident from our unsuccessful
attempts to hydrolyze compound 5 to 1ꢀunsubstituted
aminoindole. In this reaction, indole 5 is probably formed
according to a simplified scheme: N,Oꢀdeacylation in
compound 7 is followed by closure of the indole system
(Scheme 3).
Solid proof was required to confirm the structure of
compound 9 since the hypothetical intermediate A could
undergo cyclization into cinnoline derivative 11 containꢀ
ing a sixꢀmembered pyridazine ring. The elemental comꢀ
positions of compounds 9 and 11 are the same; moreover,
1H NMR data for compound 9 are not in conflict with
structure 11. However, a comparison of the 1H and
13C NMR spectra of compounds 8 and 9 suggests the
formation of the indole derivative 9. For instance, most of
the chemical shifts for compound 9 differ only slightly
In the reaction with acetic anhydride in the presence
of a catalytic amount of conc. H2SO4 (i.e., under the
conditions used earlier for Oꢀacylation of 6ꢀhydroxyꢀ3ꢀ
nitroindoles18), compound 5 undergoes opening of the
pyrrole ring through cleavage of the 1,2ꢀbond with acꢀ
companying acetylation of the OH and NH groups to give
4ꢀ(2ꢀacetoxyꢀ1ꢀnitropropꢀ1ꢀenyl)ꢀ3ꢀ[(1ꢀacetylꢀ2ꢀbenzylꢀ
idene)hydrazino]phenyl acetate (7). The above behavꢀ
ioral differences between Nꢀaminoindole derivative 5 and
the corresponding deaminated compounds should be most
reasonably associated with the destabilized ground state
of the former. Indeed, the presence of the electronꢀwithꢀ
drawing substituent (N=CHPh) at the indole N atom
partially excludes its lone electron pair from the aromatic
system, thus reducing the aromaticity of the molecule. As
the result, the indole system easily degrades to give comꢀ
pound 7. Such an opening of the pyrrole ring was detected
as an intermediate step in the transformation of an
Nꢀaminoindole derivative into substituted quinolines.19
1
The structure of compound 7 was proved by H and
13C NMR spectra, which substantially differ from those
of compound 6. First, the spectra of compound 7 show a
double set of signals due to geometrical isomers; the sigꢀ
nals were assigned from the COSY, NOESY, HSQC and
1
HMBC NMR spectra. Second, its H NMR spectrum
contains signals for four methyl groups three of which are
in acetyl radicals. In the HMBC spectrum, the latter meꢀ
thyl groups show correlation peaks with signals for C=O
at δ 168.0—171.0. The signals for the 2´ꢀmethyl group are
strongly shifted upfield (δ 1.81 and 1.90) compared to the
signals for the 2ꢀmethyl group in compound 6 (δ 2.87).
Scheme 3

1ꢀAminoindole derivatives
O(18)
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2837
Experimental
Mass spectra were recorded on a Finnigan SSQꢀ710 mass
spectrometer (direct inlet probe). 1H NMR spectra were reꢀ
corded on a Bruker ACꢀ200 spectrometer; 2D HMBC NMR
spectra were recorded on a Bruker DRXꢀ500 spectrometer in
DMSOꢀd6 with the use of Bruker standard procedures. The
course of the reactions was monitored and the purity of comꢀ
pounds was checked by TLC on Silufol UVꢀ254 plates in ethyl
acetate (spot visualization in UV light). Reflection intensities
O(16)
N(10)
O(12)
were measured on a XPert PRO powder diffractometer (CuKα
1
radiation). The crystal structure of compound 9* was solved by
the systematic search method23 and refined by the Rietweld
method with the MRIA program.24 The physicochemical charꢀ
acteristics, yields, and elemental analysis data for the compounds
obtained are given in Table 2.
1ꢀMethylꢀ2ꢀnitrovinylhydrazine (2). Hydrazine hydrate
(5.3 mL, 106 mmol) was added at 20 °C to a stirred suspension
of enamine 117 (12.2 g, 94 mmol) in 50 mL of isopropyl alcohol.
the reaction mixture was kept for 1 h and concentrated. The
residue was triturated with cooled isopropyl alcohol and the
precipitate was filtered off. The yield of compound 2 was 9.37 g.
1H NMR, δ: 2.01 (s, 3 H, Me); 5.00 (br.s, 2 H, NH2); 6.31 (s,
1 H, H(2)); 11.23 (br.s, 1 H, NH).
Fig. 1. Crystal packing of compound 9.
4ꢀ[(1ꢀMethylꢀ2ꢀnitrovinyl)hydrazono]cyclohexaꢀ2,5ꢀdienone
(3). Compound 2 (0.58 g, 5 mmol) was added to a solution of
pꢀbenzoquinone (0.54 g, 5 mmol) in 5 mL of AcOH. The reacꢀ
tion mixture was stirred at 20 °C for 2 h. The precipitate that
formed was filtered off, washed with AcOH and water, and dried
to give compound 3 (0.38 g). 1H NMR, δ: 2.45 (d, 3 H, Me, J =
1.2 Hz); 6.90, 7.70 (both m, 2 H each, C6H4); 7.95 (q, 1 H,
H(2), J = 1.2 Hz, JCH,NH = 1.2 Hz); 10.37 (br.s, 1 H, NH).
NꢀBenzylideneꢀN´ꢀ(1ꢀmethylꢀ2ꢀnitrovinyl)hydrazine (4).
Benzaldehyde (2.2 g, 21 mmol) was added at 20 °C to a stirred
suspension of compound 2 (2.5 g, 21 mmol) in 60 mL of ethaꢀ
nol. The reaction mixture was stirred for an additional 1 h. The
precipitate that formed was filtered off, washed with ethanol,
and dried to give compound 4 (3.8 g). 1H NMR, δ: 2.22 (s, 3 H,
Me); 6.74 (s, 1 H, H(2)); 7.49, 7.75 (m, 5 H, Ph); 8.61 (s, 1 H,
CHPh); 12.43 (br.s, 1 H, NH).
1ꢀBenzylideneaminoꢀ6ꢀhydroxyꢀ2ꢀmethylꢀ3ꢀnitroꢀ1Hꢀindole
(5). Toluenesulfonic acid (3.1 g, 18 mmol) and then enamine 4
(3.7 g, 18 mmol) were added at 20 °C to a stirred suspension of
pꢀbenzoquinone (1.94 g, 18 mmol) in 20 mL of AcOH. The
reaction mixture was stirred for 3 h. The precipitate that formed
was filtered off, washed with AcOH and water, and dried to give
compound 5 (1.26 g). 1H NMR, δ: 2.85 (s, 3 H, Me); 6.87 (dd,
1 H, H(5), J1 = 8.6 Hz, J2 = 1.2 Hz); 6.97 (d, 1 H, H(7), J2 =
1.2 Hz); 7.60 (m, 3 H, H(3´), H(4´), H(5´)); 8.03 (d, 2 H,
H(2´), H (6´), J1 = 7.4 Hz); 7.98 (d, 1 H, H(4), J1 = 8.6 Hz);
9.12 (s, 1 H, CHPh).
from those for compound 8, while the signals for H(5),
H(7), C(5) and C(7) are shifted upfield by 0.29, 0.61, 5.0,
and 8.4 ppm, respectively; this is due to the presence of
different substituents in position 6 of compounds 8 and 9.
This was confirmed by the difference NOE data for comꢀ
pound 9: when the Ac protons (δ 2.18) are preirradiated,
the spectra show signals for H(7) (δ 6.71) and C(2)H3
(δ 2.64), which are possible only for compound 9.
The structure of compound 9 was finally proved by
Xꢀray diffraction analysis. The threeꢀdimensional strucꢀ
ture of its molecule was determined from Xꢀray powder
diffraction data. Crystals of compound 9 are monoclinic
(space group P21/c, unit cell volume 1168(1) Å3). The
crystal packing of compound 9 is stabilized by N—H...O
and O—H...O intermolecular hydrogen bonds (Fig. 1).
Their geometric parameters are given in Table 1.
Compound 9 was also synthesized from indole 8 by its
Oꢀdeacetylation in boiling benzene in the presence of
piperidine.
Indole 10 with the unsubstituted amino group in posiꢀ
tion 1 was obtained in high yield by acid hydrolysis of its
Nꢀacyl derivative 9.
Table 1. Geometric parameters of the hydrogen bonds in comꢀ
pound 9
6ꢀAcetoxyꢀ1ꢀbenzylideneaminoꢀ2ꢀmethylꢀ3ꢀnitroꢀ1Hꢀindole
(6). A suspension of compound 5 (1.9 g, 6.4 mmol) in 20 mL of
Hydrogen bond
D—H...A
d/Å
Angle/deg
D—H...A
* All crystallographic data, including atomic coordinates and
bond lengths and angles have been deposited with the Camꢀ
bridge Crystallographic Database (No. CCDC239829). Copies
can be made available upon request to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (Fax: +44(0) 1223 336033. Eꢀmail:
deposit@ccdc.cam.ac.uk).
D—H H...A D...A
N(10)—H(10)...O(16)i
O(18)—H(18)...O(12)ii
0.86 1.89 2.73(1)
0.87 2.10 3.00(1)
162
169
Symmetry operation codes: (i) x, 1/2 – y, 1/2 + z; (ii) 1 + x, y, z.

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Lyubchanskaya et al.
Table 2. Yields, melting points, elemental analysis data, and mass spectra of compounds 2—10
Comꢀ Yield
pound (%)
M.p./°C
(solvent)
Found
Calculated
Molecular
formula
MS, m/z (Irel (%))
(%)
С
Н
N
2
3
4
5
6
85
37
88
24
70
83—85
(benzene)
111—113
(decomp.)
175—177
(EtOH)
263—265
(EtOH)
182—183
(EtOH)
30.97
30.77
51.94
52.17
58.49
58.53
65.63
65.08
64.09
64.09
5.96
6.03
4.38
4.38
5.40
5.40
4.47
4.44
4.51
4.48
35.65
35.88
—
С3H7N3O2
С9H9N3O3
117 [M]+ (58), 101 [M – NH2]+ (42),
71 [M – NO2] + (100)
207 [M]+ (26), 161 [M – NO2]+ (71),
121 [M – MeC=CHNO2]+ (100)
19.95
20.48
13.75
14.23
12.31
12.46
С10H11N3O2 205 [M]+ (29), 159 [M – NO2]+ (100),
119 [M – MeC=CHNO2]+ (93)
С16H13N3O3 295 [M]+ (100), 248 [M – HNO2]+ (10)
191 [M – PhCH=N]+ (17)
С18H15N3O4 337 [M]+ (25), 295 [M – COCH2]+ (100),
248 [M – HNO2]+ (6),
191 [M – PhCH=N]+ (13)
7
63
183—185
(EtOH)
59.88
60.13
4.82
4.81
9.64
9.56
С20H19N3O6 439 [M]+ (21), 397 [M – COCH2]+ (18),
291 [M – CHPh, —OCOCH3]+ (79),
249 [M – CHPh, —OCOCH3, —COCH2]+ (100)
С13H13N3O5 291 [M]+ (27), 249 [M – COCH2]+ (100),
207 [M – 2 COCH2]+ (24)
8
9
18
239—240
(EtOH)
262
53.48
53.61
53.03
53.01
4.55
4.50
4.60
4.45
14.15
14.43
16.49
16.86
65 (A),
90 (B) (decomp.)
С11H11N3O4 249 [M]+ (100), 207 [M – COCH2]+ (25),
190 [M – H2NCOCH3]+ (59),
(PriOH)
160 [M – H2NCOCH3, —NO]+ (27),
145 [M – H2NCOCH3, —NO, —CH3]+ (70)
10
84
295
(decomp.)
(BunOH)
52.28
52.17
4.68
4.38
19.96
20.28
С9Н9N3O3
207 [M]+ (100), 190 [M – NH3]+ (37),
160 [M – OH, —NO]+ (30),
145 [M – OH, —NO, —CH3]+ (70)
acetic anhydride was refluxed for 1 h. The reaction mixture was
cooled and diluted with water (100 mL). The precipitate that
formed was filtered off, washed with water, and dried to give
119.4 (C(5)); 119.9, 120.3 (C(6)); 125.0 (C(1´)); 128.9,
128.4, 128.6, 130.0 (Ph); 135.0 (C(2)); 144.4, 145.2 (C(2´));
148.5 (C(1)); 168.0—171.0 (NCOCH3, C(2´)CH3COO),
C(1)CH3CO).
1
compound 6 (1.5 g). H NMR, δ: 2.27 (s, 3 H, AcO); 2.87 (s,
3 H, Me); 7.20 (dd, 1 H, H(5), J1 = 8.6 Hz, J2 = 1.2 Hz); 7.59
(d, 1 H, H(7), J2 = 1.2 Hz); 7.60 (t, 2 H, H(3´), H(5´), J1 =
7.4 Hz); 7.67 (t, 1 H, H(4´), J1 = 7.4 Hz); 8.05 (d, 2 H, H(2´),
H(6´), J1 = 7.4 Hz); 8.20 (d, 1 H, H(4), J1 = 8.6 Hz); 9.14 (s,
1 H, CHPh). 13C NMR, δ: 12.3 (Me); 20.6 (CH3COO); 104.6
(C(7)); 117.3 (C(3a)); 118.8 (C(5)); 120.1 (C(4)); 125.0 (C(3));
128.9, 131.9, 130.6 (Ph); 130.6 (C(7a)); 141.2 (C(2)); 147.7
(C(6)); 166.6 (CHPh); 169.1 (CH3COO).
Compound 8. 1H NMR, δ: 2.19 (s, 3 H, C(1)NAc); 2.30 (s,
3 H, OAc); 2.66 (s, 3 H, Me); 7.16 (dd, 1 H, H(5), J1 = 8.6 Hz,
J2 = 1.2 Hz); 7.32 (d, 1 H, H(7), J2 = 1.2 Hz); 8.12 (d, 1 H,
H(4), J1 = 8.6 Hz); 11.55 (br.s, 1 H, NH). 13C NMR, δ: 11.4
(Me); 20.4, 20.8 (NCOCH3); OCOCH3); 103.8 (C(7)); 116.3
(C(3a)); 118.9 (C(5)); 120.1 (C(4)); 124.2 (C(3)); 134.2 (C(7a));
144.4 (C(2)); 147.9 (C(6)); 169.2, 169.3 (NCOCH3, OCOCH3).
1ꢀAcetylaminoꢀ6ꢀhydroxyꢀ2ꢀmethylꢀ3ꢀnitroindole
(9).
4ꢀ(2ꢀAcetoxyꢀ1ꢀnitropropꢀ1ꢀenyl)ꢀ3ꢀ[(1ꢀacetylꢀ2ꢀbenzylꢀ
idene)hydrazino]phenyl acetate (7) and 6ꢀacetoxyꢀ1ꢀacetylaminoꢀ
2ꢀmethylꢀ3ꢀnitroindole (8). One drop of conc. H2SO4 was added
at 20 °C to a stirred suspension of indole 5 (3.54 g, 12 mmol) in
40 mL of acetic anhydride. Stirring was continued for 1.5 h. The
reaction mixture was diluted with water (300 mL). The precipiꢀ
tate that formed was filtered off, washed with water, dried, and
chromatographed on silica gel with ethyl acetate as the eluent.
Compounds 7 (3.32 g) and 8 (0.65 g) were isolated in succession.
A. Concentrated HCl (1.2 mL, 14 mmol) and water (1.2 mL,
70 mmol) were added to a suspension of compound 7 (0.63 g,
1.4 mmol) in 40 mL of ethanol. The reaction mixture was reꢀ
fluxed for 30 min and concentrated. The residue was recrystalꢀ
lized from ethanol to give compound 5 (0.02 g). The ethanolic
mother liquor was concentrated, the residue was refluxed in
ethyl acetate, and the suspension was filtered hot to give comꢀ
pound 9 (0.23 g). 1H NMR, δ: 2.18 (s, 3 H, NAc); 2.64 (s, 3 H,
Me); 6.71 (d, 1 H, H(7), J2 = 1.2 Hz); 6.87 (dd, 1 H, H(5), J1 =
8.6 Hz, J2 = 1.2 Hz); 7.90 (d, 1 H, H(4), J = 8.6 Hz); 9.56 (br.s,
1 H, OH); 11.35 (br.s, 1 H, NH). 13C NMR, δ: 11.4 (Me); 20.3
(NCOCH3); 95.4 (C(7)); 111.4 (C(3a)); 113.9 (C(5)); 120.4
(C(4)); 124.4 (C(3)); 135.3 (C(7a)); 142.3 (C(2)); 155.6 (C(6));
169.0 (NCOCH3).
1
Compound 7. H NMR, δ: 1.90, 1.81 (both s, 3 H each,
C(2´)Me); 1.74, 2.10, 2.19, 2.70 (all s, 3 H each, NAc,
C(2´)OAc); 2.34 (s, 6 H, C(1)OAc); 7.70, 7.75 (both d, 1 H each,
H(2), J = 1.7 Hz); 7.06—7.37 (m, 6 H, Ph, H(5)); 7.88, 8.06
(both s, 1 H each, CHPh); 8.09, 8.15 (both d, 1 H each, H(5),
J = 8.6 Hz). 13C NMR, δ: 11.4, 11.5 (Me(2´)); 20.1, 20.4, 20.5,
20.6, 20.9, 21.12 (NCOCH3, C(2´)CH3COO, C(1)CH3CO);
79.1, 83.1 (CHPh); 105.5, 105.6 (C(2)); 116.3 (C(4)); 118.9,
B. A mixture of compound 8 (0.64 g, 2.2 mmol), benzene
(30 mL), ethanol (5 mL), and piperidine (0.37 g, 4.4 mmol) was
refluxed for 6 h and concentrated. The residue was triturated

1ꢀAminoindole derivatives
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2839
with benzene and the precipitate was filtered off and dried to
give compound 9 (0.49 g).
10. F. Schwartz and Th. WagnerꢀJauregg, Helv. Chim. Acta, 1968,
51, 1919.
1ꢀAminoꢀ6ꢀhydroxyꢀ2ꢀmethylꢀ3ꢀnitroindole (10). Concenꢀ
trated HCl (4.2 mL, 50 mmol) and water (4.5 mL, 250 mmol)
were added to a suspension of compound 8 (1.25 g, 5 mmol) in
70 mL of BunOH. The reaction mixture was refluxed for 45 min.
The resulting solution was cooled and the precipitate that formed
was filtered off, washed with BunOH, and dried to give comꢀ
pound 10 (0.76 g). The mother liquor was concentrated and the
residue was recrystallized from BunOH to give an additional
11. V. M. Lyubchanskaya, L. M. Alekseeva, S. A. Savina, A. S.
Shashkov, and V. G. Granik, Mendeleev Commun., 2004, 73.
12. G. R. Allen, Organic Reactions, Wiley Interscience, New
York, 1973, 20, 337.
13. V. G. Granik, V. M. Lyubchanskaya, and T. I. Mukhanova,
Khim.ꢀFarm. Zh., 1993, 27, No. 6, 37 [Pharm. Chem. J.,
1993, 27, No. 6 (Engl. Transl.)].
14. V. G. Granik, Organicheskaya khimiya [Organic Chemistry],
Vuzovskaya kniga, Moscow, 2003, p. 191 (in Russian).
15. V. M. Lyubchanskaya, L. M. Alekseeva, S. A. Savina, A. S.
Shashkov, and V. G. Granik, Izv. Akad. Nauk, Ser. Khim.,
2002, 1736 [Russ. Chem. Bull., Int. Ed., 2002, 51, 1886].
16. T. I. Mukhanova, E. K. Panisheva, V. M. Lyubchanskaya,
L. M. Alekseeva, Yu. N. Sheinker, and V. G. Granik, Tetraꢀ
hedron, 1997, 53, 177.
1
amount of compound 10 (0.116 g). H NMR, δ: 2.80 (s, 3 H,
Me); 5.91 (br.s, 2 H, NH2); 6.77 (dd, 1 H, H(5)); 6.95 (d, 1 H,
H(7), J = 2.0 Hz); 7.85 (d, 1 H, H(4), J = 8.4 Hz); 9.34
(br.s, 1 H, OH).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
32119).
17. R. F. Abdulla and R. S. Brinkmayer, Tetrahedron, 1979,
35, 1675.
18. V. M. Lyubchanskaya, L. M. Alekseeva, and V. G. Granik,
Khim. Geterotsikl. Soedin., 1992, 40 [Chem. Heterocycl. Comp.,
1992, 28, 34 (Engl. Transl.)].
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in revised form August 30, 2004