Azirine/oxindole ring enlargement via amidinium intermediates

Article abstract of DOI:10.1002/hlca.200490216

A novel general method for the synthesis of oxindoles, namely the 'azirine/oxindole ring enlargement via amidinium-intermediates' has been established: the reaction of 2H-azirin-3-amines 1 with BF₃· OEt₂ in THF solution at -78° leads

Full text of DOI:10.1002/hlca.200490216

Helvetica Chimica Acta Vol. 87 (2004)
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Azirine/Oxindole Ring Enlargement via Amidinium Intermediates
by Maged K. G. Mekhaela)b)1), Stefan Bienza), Anthony Lindena), and Heinz Heimgartner*a)
a) Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
b) Mubarak City for Scientific Research and Technological Applications, Alexandria, Egypt
A novel general method for the synthesis of oxindoles, namely the −azirine/oxindole ring enlargement via
amidinium-intermediates× has been established: the reaction of 2H-azirin-3-amines 1 with BF3 ¥ OEt2 in THF
solution at À 788 leads to 1,3,3-trialkyl-2-amino-3H-indolium tetrafluoroborates 14 in good yields (Scheme 5).
Treatment of aqueous solutions of 14 at 08 with aqueous NaOH (30%) and extraction with CH2Cl2 gives oily
substances that are either hydrates of 1,3,3-trialkyl-2-dihydroindol-2-imines 15 or the corresponding indolium
hydroxides. These products are transformed to the corresponding 1,3,3-trialkyl-2,3-dihydroindol-2-ones 17 in
modest yields upon refluxing in H2O/THF. Reaction of 14 with Ac2O in pyridine at ca. 238 for 16 h followed by
aqueous workup and chromatographic separation leads to mixtures of N-(1,3,3-trialkyl-2,3-dihydro-indol-2-
yliden)acetamides 16 and oxindoles 17 (Scheme 6). Hydrolysis of 16 with aqueous HCl under reflux for 1 2 h
gives oxindoles 17 in a good yield. Several oxindoles, spiro-oxindoles, and 5-substituted oxindoles were
synthesized by means of the reactions mentioned above.
Introduction.
Among numerous methods for the synthesis of oxindoles,
considerable attention has been given to reactions in which appropriate precursors
with a side chain containing a reactive center suitably positioned for the construction of
the heterocyclic ring are subjected to cyclization at the ortho-position of the aromatic
ring [1 7]. Recently, we showed that the N-phenyl residue of 2H-azirin-3-amines of
type 1 (R4 ˆ Ph) with its free ortho-position is able to act as an internal nucleophile
under the influence of the Lewis acid BF3, thereby leading to the corresponding
indolium tetrafluoroborate. The latter was converted subsequently to oxindole
derivatives [8]. Of special interest are those oxindole derivatives bearing an allyl
substituent at C(3), as they are regarded as versatile starting materials for the
preparation of 3-(aminoethyl)-1,3-dimethyloxindole, which can be converted to
desoxynoreseroline, the basic ring structure of the alkaloid physostigmine, which has
a well-established pharmacological activity [9] (and lit. cit. therein).
The first synthesis of 2H-azirin-3-amines 1 has been described by Rens and Ghosez
[10]. These strained cyclic amidines proved to be versatile building blocks for the
preparation of heterocycles, as well as peptides containing a,a-disubstituted glycines
[11]. It has been shown that each of the three ring bonds can be cleaved selectively
depending on the reaction conditions, leading to reactive intermediates such as nitrile
ylides 2 and N2-ethenylformamidines 3 (C,C cleavage), and 1,1-diaminoethenyl (−1-
azaallyl×) cations 4 (C,N cleavage; Scheme 1). In the case of the cleavage of the CˆN
bond, a-amino acid derivatives 5 are formed via an intermediate aziridine (cf. [11]). For
example, reactions of azirines 1 with carboxylic acids [10][12 14] proceed by
1
)
Part of the Ph.D. thesis of M. K. G. M., Universit‰t Z¸rich, 2003.
¹ 2004 Verlag Helvetica Chimica Acta AG, Z¸rich

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Helvetica Chimica Acta Vol. 87 (2004)
protonation and addition of the carboxylate onto the amidinium intermediate formed,
yielding an aziridine, which rearranges via ring opening to give an N-acylamino
carboxamide (cf. [14 17] and refs. cit. therein). On the other hand, reactions of 1 with
NH-acidic heterocycles (pKa < 8) lead to new heterocycles with a ring enlarged by
three atoms (NÀCÀC) [18][19], e.g., 3-oxo sultams of different ring size [20 24].
Scheme 1
The reaction of 1 with trifluoroacetamide gives 4H-imidazoles [25]. A serious
limitation of this reaction is the low acidity of carboxamides, as only substances with
pKa < 8are able to activate 1 by protonation (pKb of 1, R1 R4 ˆ Me: 7.1 [26]).
Therefore, neither benzamide nor acetamide undergo a reaction with 1. Recently, we
were able to overcome this hurdle by activating 1 with the Lewis acid BF3 [25]. The
activation of 1 by treatment with BF3 has also been used in reactions of 1 with enolates
of esters, thioesters, and carboxamides to give 1,5-dihydro-2H-pyrrol-2-ones, and even
the enolate of acetophenone reacts with the BF3 complex of 1 leading to a 2H-pyrrol-3-
amine derivative [27]. Furthermore, these complexes undergo reactions with a-amino
acid esters in which 3,6-dihydropyrazin-2(1H)-ones are formed as the main product;
the same products are obtained when 2H-azirin-3-amines 1 are reacted with a-amino
acid ester hydrochlorides [28].
In the present paper, we describe the reactions of 2H-azirin-3-amines 1 (R4 ˆ Ph)
containing an N-Ph residue with BF3 in the absence of external nucleophiles to give 2,3-
dihydro-1H-indol-2-ones (indoline-2-ones, oxindoles). The synthesis of spirocyclic
oxindoles is considered as a generalization of this novel ring-enlargement reaction.
Furthermore, new 2H-azirin-3-amines with a substituted N-Ph ring were synthesized
and transformed to 5-substituted oxindoles, which are of special interest in alkaloid
synthesis.

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Results and Discussion. 1. Synthesis of 2H-Azirin-3-amines. The carboxamides 6,
which are used as precursors in the azirine synthesis, were prepared by one of the
following methods, depending on the availability of the starting materials (Scheme 2).
In Method A, we started from commercially available acid chlorides 7, which were
reacted with the corresponding N-methylanilines. In the case of the carbocyclic
derivatives 6c 6f, the acid chlorides were prepared by treatment of the corresponding
cycloalkane carboxylic acids 8 (R1ÀR2 ˆ À(CH2)nÀ) with SOCl2 to give 7. In
Method B, carboxamides 9 were alkylated by subsequent treatment with LDA and
an alkyl halide [29]. The prepared amides 6 are collected in Table 1.
Scheme 2
Table 1. Synthesized Amides 6 and 2H-Azirin-3-amines 1 (yields in [%])
R1
R2
R3
R4
6
1
a
b
c
d
e
f
Me
Me
PhCH2
Me2CHCH2
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
3
788
80
88
95
87
89
96
8
71
86
80
55
79
87
À(CH2)3À
À(CH2)4À
À(CH2)5À
À(CH2)6À
g
h
Me
Me
Me
Me
4-MeOÀC6H4
4-NO2ÀC6H4
7
56
The 2H-azirin-3-amines 1a 1h were synthesized according to the following two
methods. According to [30], a solution of an amide 6 in dry THF at 08 under an Ar
atmosphere was treated with LDA, and, after 1 h, the amide enolate 10 formed was
treated with diphenyl phosphorochloridate (diphenylphosphoryl chloride, DPPCl) at
08. A smooth reaction took place, leading to the corresponding chloroenamines 11.
Under an Ar atmosphere, the suspension was filtered into a suspension of NaN3 in dry

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Helvetica Chimica Acta Vol. 87 (2004)
DMF. After 3 4 d at room temperature, the 2,2-disubstituted 2H-azirin-3-amines 1a
1g were obtained (Scheme 3 and Table 1).
Scheme 3
Compounds 1a 1f have already been synthesized and fully characterized either by
this method [30] or with COCl2 according to the procedure described in [31]. The new
azirine 1g was fully characterized by spectroscopic methods and elemental analysis (see
Exper. Part).
On the other hand, amide 6h was treated with Lawesson reagent to give the
corresponding thioamide 12h in 87% yield (cf. [31]). The latter was subsequently
dissolved in CH2Cl2 containing one drop of DMF, and a solution of COCl2 in toluene
was added dropwise at 08. Then, the solvent was evaporated and the residue was
dissolved in THF. After addition of 1,4-diaminobicyclo[2.2.2]octane (DABCO), the
precipitate was separated by filtration, the solution containing the chloroenamine 11h
was evaporated, and a solution of NaN3 in DMF was added. After 2 weeks, 1h was
obtained in 56% yield (Scheme 3).
It is worth mentioning that an improvement of the published method for
synthesizing 1 via the thioamides [31 33] was achieved by performing the reaction
of 11 with NaN3 in DMF instead of THF and by increasing the reaction time to two
weeks. Furthermore, the chloro-enamine 11h could be isolated by carrying out the
reaction of 12 (Arˆ 4-NO2ÀC6H4) with COCl2 and DABCO in THF for 4 d.
The structures of the thioamide 12h, the chloro-enamine 11h, and the azirine 1h
were established on the basis of their spectroscopic data and elemental analyses. The IR
spectra of the new azirines 1g and 1h showed a strong absorption band at 1753 and

Helvetica Chimica Acta Vol. 87 (2004)
2389
1742 cmÀ1, respectively, which is characteristic of the CˆN stretching of the azirine
ring. Furthermore, 1g and 1h were characterized chemically by making use of the
characteristic reaction with thiobenzoic acid (cf. [33 38]). The resulting thioamides
13a and 13b were isolated, after chromatographic workup (SiO2), in analytically pure
form in 88 and 92% yield, respectively (Scheme 4).
Scheme 4
The structures of 13a and 13b were elucidated on the basis of their spectroscopic
data. The IR spectra are characterized by strong absorption bands at 3258and
3293 cmÀ1 for NÀH, and at 1637 and 1642 cmÀ1, respectively, for the amide CˆO
group. The 13C-NMR spectra show singlets at 209.1 and 209.4 ppm for CˆS, and 165.0
and 165.4 ppm for CˆO, respectively. The Me groups of 13a appear in the 13C-NMR
spectrum at 55.3 and 51.7 ppm (MeO and MeN) and at 29.0 ppm for Me2C. In the
1H-NMR spectrum, MeO and MeN absorb both at 3.74 ppm, and the signal for Me2C
appears at 1.76 ppm. In the case of 13b, the signals of the MeN and Me2C groups are
found at 3.72/49.4 and 1.86/30.7 ppm, respectively.
2. Reaction of 2H-Azirin-3-amines 1 with BF3. The reaction of 1 (R3 ˆ Me, R4 ˆ
Ar) with BF3 in the absence of external nucleophiles was carried out by addition of an
equimolar amount of BF3 ¥ OEt2 to a stirred solution of 1 in THF at À 788. The mixture
was allowed to warm to room temperature and stirred for 12 h. After addition of Et2O,
solid products were filtered off and recrystallized, whereas oily materials were purified
by chromatography (SiO2; CH2Cl2/MeOH) to give 2-amino-1,3,3-trialkyl-3H-indolium
tetrafluoroborates 14 in good yields [39] (Scheme 5 and Table 2).
Scheme 5

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Table 2. Synthesized 3H-Indolium Tetrafluoroborates 14 (yields in [%])
1
R1
R2
R
14
a
b
c
d
e
f
Me
Me
PhCH2
Me2CHCH2
H
H
H
H
H
H
MeO
NO2
91
62
8
56
59
60
42
26
À(CH2)3À
À(CH2)4À
À(CH2)5À
À(CH2)6À
4
g
h
Me
Me
Me
Me
The structures of the indolium tetrafluoroborates 14 formed have been established
on the basis of spectroscopic data, elemental analyses, and, in the case of 14f, by an X-
ray crystal-structure determination. The IR spectra of the salts 14 show two
characteristic absorption bands in the region of 3400 3200 cmÀ1 for NÀH stretching
vibrations of the NH2 group, and an intense CˆN absorption band at 1695 1680 cmÀ1.
1
The H- and 13C-NMR spectra were recorded mainly in (D6)DMSO. In general, the
1H-NMR spectra show two broad singlets for the NH2 group and a singlet at 3.63
3.24 ppm for MeN. In the 13C-NMR spectra, a singlet at 176.1 174.8ppm for C(2) of
the indole ring was observed. This signal is shifted upfield to 164.8in 14c and to
170.1 ppm in 14h. Two signals at 56.3 46.8( s) for C(3) and at 29.5 28.6 ppm (q) for
MeN are shifted downfield to 61.2 and 45.2 for 14c, and to 58.2 and 40.0 ppm for 14h.
1
The H-NMR spectrum of 14b in CDCl3 shows that the H-atoms of the Me2CHCH2
group are not equivalent and appear at 2.38 2.28 and 2.09 2.00 ppm as an ABX
system; the Me groups of the side chain absorb as doublets at 0.73 and 0.55 ppm. The
‡
most-characteristic peak in the CI-MS of compounds 14 is that for [M À BF4] , which,
in general, is the base peak. The EI-MS of 14a, 14b, and 14d give useful information
about the fragmentation pattern of this class of compounds. In all cases, m/z 159 is a
dominant peak.
The crystal structure of the spirocyclic 14f is shown in Fig. 1. The indole ring system
(N(1) to C(9)) is almost planar with C(10) and N(2) also being in this plane. In
addition, the exocyclic NH2 group is coplanar with the heterocyclic ring, and the short
N(1),C(2) and N(2),C(2) bonds (1.326(2) and 1.310(2) ä, resp.) indicate a distinct p-
conjugation in the amidinium moiety. On the other hand, the N(1),C(9) and N(2),C(2)
bonds are normal single bonds (1.424(2) and 1.459(2) ä, resp.; see Table 5). Each H-
atom of the NH2 group of the cation forms an interionic H-bond with an F-atom of a
neighboring BFÀ4 anion in such a way that each cation interacts with two different
acceptor anions that are related to each other by a crystallographic center of inversion.
In turn, each anion, via two F-atoms, accepts two H-bonds, one being from each of two
different centrosymmetrically related cations. The combination of these interactions
links two cations and two anions into a closed tetrameric H-bonded loop with a graph
set motif [40] of R44(12).
3. Synthesis of Oxindoles and Related Compounds. Treatment of aqueous solutions
of 14 at 08 with aqueous NaOH (30%) and subsequent extraction with CH2Cl2 gave oily
substances of type 15 in high yield, which, according to the spectroscopic data and, in
the case of 15b, elemental analysis, were either hydrates of 3,3-dialkyl-2,3-dihydro-1-

Helvetica Chimica Acta Vol. 87 (2004)
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Fig. 1. ORTEP Plot [41] of the molecular structure of 14f (arbitrary numbering of the atoms; 50% probability
ellipsoids)
methyl-1H-indol-2-imines or the corresponding indolium hydroxides (Scheme 6 and
Table 3). In the IR spectra, the hydrates 15 show absorption bands in the region of
3305 3275 cmÀ1 for NÀH stretching vibrations and an intense CˆN band at 1651
‡
1635 cmÀ1. The CI-MS show the base peak for [M ‡ 1 À H2O] , whereas in the EI-MS a
‡
peak for [M À H2O] is observed. The 13C-NMR spectra of compounds 15 are very
similar to those of the corresponding tetrafluoroborates 14.
Treatment of 14 with Ac2O in pyridine at ca. 238 for 16 h followed by aqueous
workup and chromatographic separation (SiO2), yielded mixtures of N-(3,3-dialkyl-
2,3-dihydro-1-methyl-1H-indol-2-yliden)acetamides 16 and 1,3-dihydro-2H-indol-2-
ones (oxindoles) 17 (Scheme 6 and Table 3).
Most likely, the initially formed N-acetyl derivative 16 was partly hydrolyzed under
the workup conditions to give 17. The latter could be obtained in good yield by the
hydrolysis of 16 with aqueous HCl under reflux for 1 2 h. The hydrolysis of 16b was
carried out under milder conditions by stirring in 10% HCl solution at room
temperature overnight to avoid the loss of the side chain2). It is worth mentioning that
compounds 16 were also obtained from the hydrates 15 upon treatment with Ac2O in
pyridine. Furthermore, the oxindole derivatives 17 were accessible by hydrolysis of the
hydrates 15 in H2O/THF (Scheme 6). The yields of this hydrolysis as well as those of the
N-acetyl derivatives 16 are listed in Table 4.
2
)
This undesired side reaction has been observed under more-drastic reaction conditions.

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 6
Table 3. Synthesis of Hydrates 15, N-Acetyl Derivatives 16, and Oxindoles 17 from 3H-Indolium Tetrafluoro-
borates 14 (yields in [%])
14
R1
R2
R
15
16
17
a
b
c
d
e
f
Me
Me
PhCH2
Me2CHCH2
H
H
H
H
H
H
MeO
NO2
95
88
94
92
96
96
99
42
34
16
16
53
41
32
À(CH2)3À
À(CH2)4À
À(CH2)5À
À(CH2)6À
50
57
48
24
29
31
g
h
Me
Me
Me
Me
39
5
Table 4. Yields of Oxindoles 17 [%] from the Hydrolyses of 15 (H2O/THF) and 16 (aq. HCl)
17
R1
R2
R
From 15
From 16
a
b
c
d
e
f
Me
Me
PhCH2
Me2CHCH2
H
H
H
H
H
H
MeO
NO2
92
94
8
94
91
8
8
8
8
0
À(CH2)3À
À(CH2)4À
À(CH2)5À
À(CH2)6À
7
9
94
93
8
6
g
h
Me
Me
Me
Me
95
89
34
The IR spectra of the acetyl derivatives 16 show a characteristic group of three
strong absorption bands at 1720 1665, 1660 1635, and 1615 1600 cmÀ1. The first two
correspond to CˆO (amidic) and CˆN stretching vibrations of the N-acetyl group,
whereas the third band, together with another strong band at 1505 1490 cmÀ1,
indicates the aromatic nature of the compounds. In the 1H-NMR spectra, characteristic

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Fig. 2. ORTEP Plots [41] of the molecular structures of a) 16a and b) 17a (arbitrary numbering of the atoms;
50% probability ellipsoids)

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Helvetica Chimica Acta Vol. 87 (2004)
signals are detected at 3.41 2.89 ppm for MeN and at 2.49 2.28 ppm for MeCO. In the
13C-NMR spectra, characteristic singlets appear at 181.8 180.1 (CˆO), 167.3 163.8
‡
(CˆN), and 56.1 46.4 ppm (C(3)). The CI-MS show the base peak at [M ‡ 1] . In the
EI-MS fragmentation pattern of the acetyl derivative 16b, a McLafferty rearrangement
leads to the loss of isobutene to give a peak at m/z 202 (88). The base peak is at m/z 160.
In addition, the structure of 16a has been established by an X-ray crystal-structure
determination (Fig. 2).
In the crystal structure of 16a, the two fused rings are essentially planar, although
C(2) deviates by 0.10 ä from the mean plane defined by the other eight ring atoms. As
a result, the atoms of the substituent at C(2), namely N(2) and C(11), also deviate
significantly from the ring plane. The CˆO group is not coplanar with the CˆN group,
indicating a lack of conjugation between the CˆO group and the amidine moiety of the
molecule. For comparison, the C,N bond lengths of 16a are listed in Table 5, together
with those of the indolium tetrafluoroborate 14f and the oxindole 17a.
Table 5. CÀN Bond Lengths [ä] in the Crystal Structures of 14f, 16a, and 17a
CÀN Bond
14f
16a
17a
N(1)ÀC(2)
N(1)ÀC(9)
N(1)ÀC(10)
N(2)ÀC(2)
N(2)ÀC(11)
1.326(2)
1.424(2)
1.459(2)
1.310(2)
1.368(3)
1.407(2)
1.452(2)
1.284(2)
1.381(2)
1.370(3)
1.405(2)
1.452(3)
The structures of the oxindoles of type 17 were also elucidated from spectroscopic
data and elemental analyses. The IR spectra show strong absorptions at 1725
1700 cmÀ1 for amide CˆO and at 1615 1600, 1496 1490 cmÀ1 for the aromatic ring.
In the 1H-NMR spectra (CDCl3), the typical signals of the aromatic, alkyl, or
spirocyclic part at C(3), and a characteristic singlet at 3.28 2.98ppm for MeN are
present. The 13C-NMR spectra show two singlets at 182.3 179.8 (CˆO) and 53.8
44.1 ppm (C(3)), and a quadruplet at 26.7 25.7 ppm for MeN. In the CI-MS (NH3), the
‡
‡
most-important peaks are [M ‡ NH4] and [M ‡ 1] , whereas the EI-MS show the
.
‡
molecular ion (M ) and m/z 160 as the base peak. Finally, the structure of 17a has been
established by a low-temperature X-ray crystal-structure determination (Fig. 2). The
fused rings together with O(2) form a planar system. The C,N bond lengths involving
N(1) are almost identical with those of the N-acetyl derivative 16a (Table 5).
The mechanisms of the BF3-catalyzed ring enlargement of 2H-azirin-3-amines 1 to
indolium tetrafluoroborates and the subsequent transformation of the latter to
oxindoles were discussed in [8].
We thank the analytical units of our institute for spectra and analyses. Financial support of this work by the
Swiss National Science Foundation and F. Hoffmann-La Roche AG, Basel, is gratefully acknowledged.
Experimental Part
1. General. Solvents were purified by standard procedures. TLC: Merck TLC aluminium sheets, silica gel 60
F254. Prep. TLC: Merck PLC plates (glass), silica gel 60 F254, 2 mm. Column chromatography (CC): Uetikon-
Chemie −Chromatographiegel× C-560. M.p.: Mettler-FP-5 apparatus or B¸chi 510 apparatus; uncorrected. IR

Helvetica Chimica Acta Vol. 87 (2004)
2395
1H-
Spectra: Perkin-Elmer-781 spectrophotometer or Perkin-Elmer-1600-FT-IR spectrophotometer; in cmÀ1
.
(300 MHz) and 13C-NMR (75.5 MHz) Spectra: Bruker ARX-300 instrument; at 300 K in CDCl3, if not
otherwise stated; d in ppm, J in Hz; 13C-signal multiplicity from DEPT spectra. MS: Finnigan SSQ-700 or MAT-
90 instrument for CI (NH3); m/z (rel. %).
Amides 6 and 2H-azirin-3-amines 1 reported in this paper were prepared according to known protocols.
Only the syntheses of amides 6g and 6h, and the preparation of the new azirines 1g and 1h will be described.
2. Synthesis of Amides 6. To a soln. of a 4-substituted N-methylaniline (1 equiv.) in dry dioxane containing
Et3N (1.2 equiv.), 2-methylpropanoyl chloride (1.2 equiv.) was added. The stirred mixture was heated under
reflux for 2 h and left to cool to r.t. Then, the solvent was evaporated, and the residue was dissolved in CHCl3,
washed with aq. HCl (2%), sat. aq. NaHCO3 soln., and brine, and dried (Na2SO4). The solvent was evaporated
i.v., and the crude product was distilled or crystallized.
N-(4-Methoxyphenyl)-2,N-dimethylpropanamide (6g). 4-Methoxy-N-methylaniline (5 g, 36.4 mmol), dry
dioxane (100 ml), Et3N (6.1 ml, 43.8mmol), and 2-methylpropanoyl chloride (4.62 ml, 43.8mmol). Bulb-to-
bulb distillation at 1308/2 ¥ 10À3 Torr yielded 7.25 g (96%) of 6g. Pale yellow oil, which crystallized in h.v. IR
(KBr): 3041w, 2969s, 2935m, 2874m, 2839m, 1652s, 1609m, 1584m, 1512s, 1470s, 1444m, 1423m, 1387s, 1361m,
1291s, 1269s, 1248s, 1182m, 1170m, 1119s, 1107m, 1093m, 1039s, 964w, 921w, 8 39s, 798w, 751w, 733w, 692w, 599m.
1H-NMR: 7.10, 6.92 (AA'BB', 4 arom. H); 3.83 (s, MeO); 3.22 (s, MeN); 2.57 2.45 (m, CH); 1.00 (d, J ˆ 7, 2
Me). 13C-NMR: 177.7 (s, CˆO); 158.9, 137.1 (2s, 2 arom. C); 128.3, 114.9 (2d, 4 arom. CH); 55.5 (q, MeO); 37.6
‡
‡
(q, MeN); 30.9 (d, CH); 19.7 (q, 2 Me). CI-MS: 416 (14), 415 (49, [2 M ‡ 1] ), 209 (14), 208(100, [ M ‡ 1] ), 207
.
‡
(18, M ), 137 (13).
2,N-Dimethyl-N-(4-nitrophenyl)propanamide (6h). N-Methyl-4-nitro-aniline (2.38g, 15.6 mmol), dry
dioxane (40 ml), Et3N (2.6 ml, 18.7 mmol), and 2-methylpropanoyl chloride (2 ml, 18.9 mmol). Crystallization
from hexane/Et2O yielded 3.02 g (87%) of 6h. Yellow solid. M.p. 1038. IR (KBr): 3107w, 3063w, 2967m, 2934m,
2872w, 1950w, 1662s, 1605s, 1592s, 1518s, 1496s, 1466m, 1421m, 1384m, 1343s, 1325m, 1298s, 1265s, 1171w, 1108m,
1092m, 1030m, 920w, 8 68m, 8 49m, 763w, 746w, 703m. 1H-NMR: 8.20, 7.36 (AA'BB', 4 arom. H); 3.24 (s, MeN);
2.61 2.46 (m, CH); 0.99 (d, J ˆ 6.7, 2 Me). 13C-NMR: 176.7 (s, CˆO); 149.9, 146.1 (2s, 2 arom. C); 127.6, 124.8
.
‡
(2d, 4 arom. CH); 37.2 (q, MeN); 31.2 (d, CH); 19.4 (q, 2 Me). EI-MS: 222 (1, M ), 152 (5), 105 (4), 43 (100),
41 (28).
3. Synthesis of 2,N-Dimethyl-N-(4-nitrophenyl)propanethioamide (12h). To
a soln. of 6h (2.3 g,
10.35 mmol) in abs. toluene (23 ml) was added Lawesson reagent (2.3 g, 5.69 mmol), and the mixture was
heated at 908 for 1 h. After cooling to r.t., the solvent was evaporated, and the crude product was purified by CC
(AcOEt/hexane 3 :10) to give 2.15 g (87%) of 12h. Pale yellow powder. M.p. 149.0 149.68. IR (KBr): 3100w,
3057w, 3035w, 2969m, 2928m, 2863m, 1608s, 1591s, 1528s, 1490s, 1451s, 1383s, 1349s, 1325s, 1310s, 1274s, 1204m,
1101s, 1034s, 1008s, 8 93w, 8 70s, 8 58m, 760m, 701s, 663w, 629w, 602w. 1H-NMR: 8.35, 7.38 (AA'BB', 4 arom. H);
3.73 (s, MeN); 2.91 2.75 (m, CH); 1.15 (d, J ˆ 6.5, 2 Me). 13C-NMR: 213.7 (s, CˆS); 147.5, 145.2 (2s, 2 arom.
C); 126.9, 125.4 (2d, 4 arom. CH); 45.3 (q, MeN); 38.8 (d, CH); 23.6 (q, 2 Me). CI-MS: 240 (13), 239 (100, [M ‡
‡
1] ), 210 (6), 209 (46), 208(9). Anal. calc. for C 11H14N2O2S (238.31): C 55.44, H 5.92, N 11.75, S 13.45; found: C
55.41, H 5.82, N 11.73, S 13.17.
4. Synthesis of 2H-Azirin-3-amines. General Procedure 1 (GP 1). To a stirred soln. of (i-Pr)2NH (1.1 equiv.)
in THF at À 208, BuLi (2m soln. in pentane, 1.1 equiv.) was added under Ar, and the mixture was allowed to
warm to 08. Then, a soln. of the corresponding amide 6 (1 equiv.) in 5 ml THF was added dropwise, the mixture
was stirred at 08 for 1 h, and diphenyl phosphorochloridate (diphenoxyphosphoryl chloride, DPPCl; 1.03 equiv.)
was added dropwise. After 30 min, the ice bath was removed, and the mixture was stirred for 24 h. The
precipitate formed was removed by filtration under Ar, and the THF soln. was dropped into a suspension of
NaN3 (3 equiv.) in dry DMF. The mixture was stirred for 4 d at r.t. Then, Et2O was added, the mixture was
filtered over a Celite pad, the solvent was evaporated, and the residue was dissolved in Et2O. The soln. was
washed twice with 5% aq. NaHCO3 soln., and the aq. layer was extracted with Et2O. The combined org. layers
were dried (MgSO4), the solvent was evaporated i.v., and the crude product was purified by bulb-to-bulb
distillation and/or CC.
4.1. N-(4-Methoxyphenyl)-2,2,N-trimethyl-2H-azirin-3-amine (1g). According to GP 1, with 6g (3.43 g,
16.57 mmol), THF (83 ml), (i-Pr)2NH (2.7 ml, 19.05 mmol), BuLi (2m soln. in pentane, 9.2 ml, 18.4 mmol),
DPPCl (3.5 ml, 17.06 mmol), NaN3 (3.23, 49.68mmol), and DMF (8.3 ml). Distillation at 110 8/2 ¥ 10¥3 Torr,
followed by CC (AcOEt/hexane 1 :2), yielded 2.93 g (87%) of 1g. Slightly yellow oil. IR (film) : 3050m, 2941s,
2836s, 1753s, 1649m, 1587m, 1512s, 1463s, 1370s, 1282s, 1248s, 1183s, 1125s, 1092s, 1033s, 950s, 825s, 791m, 773m,
677w, 654w, 639m, 610s. 1H-NMR: 7.02, 6.91 (AA'BB', 4 arom. H); 3.80 (s, MeO); 3.40 (s, MeN); 1.42 (s, 2 Me).
13C-NMR: 155.8, 136.4 (2s, 2 arom. C); 117.9, 114.7 (2d, 4 arom. CH); 55.6 (q, MeO); 37.4 (q, MeN); 25.5 (q, 2

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Helvetica Chimica Acta Vol. 87 (2004)
‡
Me); C(2) and C(3) could not be detected. CI-MS: 206 (14), 205 (100, [M ‡ 1] ), 138(5). Anal. calc. for
C12H16N2O (204.27): C 70.56, H 7.90, N 13.71; found: C 70.58, H 7.82, N 13.75.
4.2. 2,2,N-Trimethyl-N-(4-nitrophenyl)-2H-azirin-3-amine (1h). 4.2.1. N-(1-Chloro-2-methylprop-1-enyl)-
N-methyl-4-nitrobenzenamine (11h). To a stirred soln. of 12h (4.74 g, 19.89 mmol) in abs. CH2Cl2 (77 ml) and
0.64 ml of DMF at 08 was added a soln. of COCl2 in toluene (2n, 13 ml, 26 mmol). The mixture was stirred at
08 ! r.t. for 1 h, the solvent was evaporated, the residue was dissolved in abs. THF (77 ml), and 1,4-
diazabicyclo[2.2.2]octane (DABCO; 3.2 g, 28.53 mmol) was added. After stirring for 60 min at r.t., the mixture
was filtered under N2, the residue was washed with absolute THF, and the pale yellow soln. was evaporated. The
chloro-enamine 11h was obtained as a yellow oil. It was characterized and immediately used in the subsequent
reaction.
Data of 11h: IR (KBr): 3087w, 2995w, 2915w, 2825w, 2664w, 1595s, 1502s, 1470m, 1451w, 1315s, 1241m,
1189m, 1108s, 991m, 8 60m, 8 36m, 793m, 753m, 693w, 676w, 644w. 1H-NMR: 8.12, 6.77 (AA'BB', 4 arom. H); 3.15
(s, MeN); 1.94, 1.70 (2s, 2 Me). 13C-NMR: 151.1, 139.7 (2s, 2 arom. C); 132.0 (s, ˆCMe2); 128.5 (s, ˆCCl); 125.7,
‡
112.5 (2d, 4 arom. CH); 37.2 (q, MeN); 20.6, 19.4 (2q, 2 Me). CI-MS: 261 (4), 260 (33, [M ‡ NH4] ), 243 (10,
‡
‡
‡
[M ‡ 1] ) for 37Cl isotope, and 259 (13), 258(100, [ M ‡ NH4] ), 241 (31, [M ‡ 1] ) for 35Cl isotope, 227 (5), 225
(16), 224 (7), 206 (6), 205 (44). Anal. calc. for C11H13ClN2O2 (240.69): C 54.89, H 5.44, N 11.64, Cl 14.73; found:
C 54.99, H 5.51, N 11.96, Cl 14.22.
Compound 1h: The chloro-enamine 11h was dissolved in DMF (25 ml), NaN3 (3.91 g, 60.39 mmol) was
added, and the mixture was stirred at r.t. for 2 weeks. Then, it was filtered through a Celite pad, the column was
washed with Et2O, and the solvent was evaporated. The crude product was purified by CC (AcOEt/hexane 2 :5):
2.46 g (56%) of 1h. Yellow solid. M.p. 116.1 117.38. IR (KBr): 3117w, 3075w, 2977w, 2948m, 2919m, 1742s,
1652w, 1599s, 1499s, 1451s, 1423m, 1391m, 1376m, 1314s, 1225s, 1184m, 1122s, 1110s, 946m, 8 37s, 752s, 68 8m,
628m. 1H-NMR: 8.27 (AA'BB', 2 arom. H); 7.31 (m, 2 arom. H); 3.52 (s, MeN); 1.49 (s, 2 Me). 13C-NMR: 168.1
(s, CˆN); 147.4, 142.6 (2s, 2 arom. C); 125.4, 115.1 (2d, 4 arom. CH); 25.2 (q, 2 Me); C(2) and MeN could not be
‡
‡
detected. ESI-MS: 243 (14), 242 (100, [M ‡ Na] ), 220 (13, [M ‡ 1] ). Anal. calc. for C11H13N3O2 (219.246): C
60.26, H 5.98, N 19.17; found: C 60.34, H 6.19, N 19.19.
5. Reaction of 2H-Azirin-3-amines 1 with BF3 ¥ OEt2. General Procedure 2 (GP 2). To a stirred soln. of 1 (1
equiv.) in THF at À 788, BF3 ¥ OEt2 (ca. 48 % BF in Et2O; 1.0 1.1 equiv.) was added. Then, the mixture was
3
allowed to warm slowly to ca. 238 and was stirred for 12 h at this temp. After addition of Et2O and filtration, the
crude product was purified by crystallization or CC (SiO2) to give 14.
5.1. 2-Amino-3-benzyl-1,3-dimethyl-3H-indolium Tetrafluoroborate (14a). According to GP 2, with 1a
(300 mg, 1.20 mmol), THF (30 ml), and BF3 ¥ OEt2 (0.32 ml, 1.22 mmol). CC (MeOH/CH2Cl2 1 :10) yielded
370 mg (91%) of 14a. Colorless viscous oil, which forms a foam in h.v. IR (film): 3379s, 3317s, 3246s, 3063s,
3033s, 2980s, 2937s, 2876m, 1694s, 1615s, 1496s, 1472s, 1455s, 1423s, 1385m, 1304m, 1047s, 916w, 8 43w, 761s, 726m,
703s. 1H-NMR: 7.37 (br. s, NH2); 7.32 7.15, 7.04 6.94, 6.88 6.83, 6.80 6.75 (4m, 9 arom. H); 3.25 (s, PhCH2);
3.24 (s, MeN); 1.67 (s, Me). 13C-NMR: 174.8( s, CˆN); 141.9, 134.0, 133.5 (3s, 3 arom. C); 129.5, 128.9, 127.8,
127.1, 124.9, 123.4, 110.0 (7d, 9 arom. CH); 52.9 (s, C(3)); 44.6 (t, PhCH2); 28.6 (q, MeN); 22.3 (q, Me). EI-MS:
‡
251 (6, [M À BF4] ), 250 (25), 160 (14), 159 (100), 144 (9), 143 (10), 134 (28), 117 (11), 91 (17), 77 (7). Anal.
calc. for C17H19BF4N2 (338.15): C 60.38, H 5.66, N 8.28; found: C 60.39, H 5.77, N 7.99.
5.2. 2-Amino-1,3-dimethyl-3-(2-methylpropyl)-3H-indolium Tetrafluoroborate (14b). According to GP 2,
with 1b (826 mg, 3.8 mmol), THF (83 ml), and BF3 ¥ OEt2 (1.0 ml, 3.8mmol). CC (MeOH/CH 2Cl2 0.5 :10)
yielded 720 mg (62%) of 14b. Thick colorless oil, which gives a white solid in h.v. M.p. 156.5 157.58. IR (KBr):
3391m, 3321m, 3256s, 3210m, 2963s, 2873m, 1683s, 1608s, 1504m, 1473s, 1423m, 1390m, 1368w, 1353w, 1306m,
1263w, 1242w, 1191m, 1084s, 937w, 8 37w, 766s, 756s, 699w. 1H-NMR: 8.76, 8.52 (2 br. s, NH2); 7.45 7.36, 7.32
7.25 (2m, 3 arom. H); 7.13 (d-like, 1 arom. H); 3.63 (s, MeN); 2.38 2.28, 2.09 2.00 (2 m, CH2); 1.61 (s, Me);
1.26 1.09 (m, CH); 0.73, 0.55 (2d-like, J ˆ 6.6, 2 Me). 13C-NMR: 176.1 (s, CˆN); 141.6, 134.7 (2s, 2 arom. C);
128.8, 125.7, 122.9, 110.6 (4d, 4 arom. CH); 51.7 (s, C(3)); 46.3 (t, CH2); 29.3 (q, MeN); 26.3 (q, Me); 25.4 (d,
‡
CH); 23.5, 22.7 (2q, 2 Me). EI-MS: 217 (4, [M À BF4] ), 216 (14), 173 (20), 161 (10), 160 (100), 159 (97), 144
(11), 130 (13), 117 (13), 106 (13), 100 (10). Anal. calc. for C14H21BF4N2 (304.13): C 55.29, H 6.96, N 9.21; found:
C 55.51, H 6.84, N 9.10.
5.3. 2'-Amino-1'-methylspiro[cyclobutane-1,3'-[3H]indolium] Tetrafluoroborate (14c). According to GP 2,
with 1c (555 mg, 2.98mmol), THF (50 ml), and BF 3 ¥ OEt2 (0.78ml, 2.98mmol). Filtration and washing of the
precipitate with Et2O yielded 686 mg (84%) of 14c. White powder. M.p. 179.5 180.58. IR (KBr): 3332s, 2966m,
1634s, 1591s, 1492m, 1456s, 1281m, 1063s, 8 54w, 778m, 703s, 604w. 1H-NMR ((D6)DMSO): 7.63 7.43 (m, 4 arom.
H); 5.52 (br. s, NH2); 3.51 (s, MeN); 2.35 2.25 (t-like, 4 H); 2.03 1.82, 1.48 1.31 (2m, 1 H each). 13C-NMR
((D6)DMSO): 164.8( s, CˆN); 143.8( s, 1 arom. C); 130.0, 128.4, 125.8 (3d, 4 arom. CH); 61.2 (s, C(3)); 45.2 (q,

Helvetica Chimica Acta Vol. 87 (2004)
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‡
MeN); 35.5 (t, 2 CH2); 14.1 (t, CH2). CI-MS: 188 (10), 187 (100, [M À BF4] ), 172 (47), 171 (13), 108(58), 107
(11). Anal. calc. for C12H15N2BF4 (274.07): C 52.59, H 5.52, N 10.22; found: C 52.48, H 5.68, N 10.10.
5.4. 2'-Amino-1'-methylspiro[cyclopentane-1,3'-[3H]indolium] Tetrafluoroborate (14d). According to
GP 2, with 1d (629 mg, 3.14 mmol), THF (65 ml), and BF3 ¥ OEt2 (0.83 ml, 3.17 mmol). Filtration and washing
of the precipitate with Et2O yielded 510 mg (56%) of 14d. White powder. M.p. 212 212.58. IR (KBr): 3378s,
3313m, 3242s, 3215s, 3159m, 3064m, 2964s, 2884m, 1690s, 1611s, 1596m, 1505m, 1469s, 1459s, 1422m, 1355m,
1324m, 1299m, 1268w, 1149s, 1112s, 1041s, 1003s, 938w, 8 68w, 767s, 760s, 740w, 678s. 1H-NMR ((D6)DMSO): 9.78
(br. s, NH2); 7.51 7.41 (m, 2 arom. H); 7.35 (d-like, 1 arom. H); 7.25 (t-like, 1 arom. H); 3.49 (s, MeN); 2.19 1.89
(m, 4 CH2). 13C-NMR ((D6)DMSO): 175.7 (s, CˆN); 141.3, 137.4 (2s, 2 arom. C); 128.1, 125.1, 122.4, 110.5 (4d, 4
‡
arom. CH); 56.3 (s, C(3)); 39.1, 25.5 (2t, 4 CH2); 29.4 (q, MeN). EI-MS: 201 (4, [M À BF4] ), 200 (12), 160 (9),
159 (100), 144 (12). Anal. calc. for C13H17BF4N2 (288.09): C 54.20, H 5.95, N 9.72; found: C 53.96, H 5.96, N 9.54.
5.5. 2'-Amino-1'-methylspiro[cyclohexane-1,3'-[3H]indolium] Tetrafluoroborate (14e). According to GP 2,
with 1e (619 mg, 2.89 mmol), THF (62 ml), and BF3 ¥ OEt2 (0.84 ml, 3.21 mmol). Crystallization from EtOH
yielded 514 mg (59%) of 14e. White powder. M.p. 246.5 247.58. IR (KBr): 3389s, 3256s, 2942s, 2865s, 1682s,
1607s, 1505s, 1469s, 1350s, 1311s, 1272m, 1048s, 936m, 8 47w, 750s, 692m. 1H-NMR ((D6)DMSO): 9.95, 9.74 (2 br.
s, NH2); 7.84 (d-like, 1 arom. H); 7.48( t-like, 1 arom. H); 7.37 (d-like, 1 arom. H); 7.23 (t-like, 1 arom. H); 3.49 (s,
MeN); 1.98 1.75, 1.65 1.56 (2 m, 5 CH2). 13C-NMR ((D6)DMSO): 175.1 (s, CˆN); 141.8, 134.6 (2s, 2 arom. C);
128.4, 125.1, 124.3, 111.0 (4d, 4 arom. CH); 50.3 (s, C(3)); 32.4, 23.9, 20.3 (3t, 5 CH2); 29.5 (q, MeN). CI-MS: 216
‡
(16), 215 (100, [M À BF4] ). Anal. calc. for C14H19BF4N2 (302.12): C 55.66, H 6.34, N 9.27; found: C 55.39, H
6.38, N 9.20.
5.6. 2'-Amino-1'-methylspiro[cycloheptane-1,3'-[3H]indolium] Tetrafluoroborate (14f). According to GP 2,
with 1f (263 mg, 1.15 mmol), THF (26 ml), and BF3 ¥ OEt2 (0.32 ml, 1.22 mmol). Crystallization from EtOH
yielded 220 mg (60%) of 14f. Colorless needles. M.p. 237.5 238.58. Crystals suitable for an X-ray crystal-
structure determination were grown from EtOH. IR (KBr): 3392s, 3320m, 3254s, 2990m, 2929s, 2863m, 1686s,
1609s, 1501m, 1468s, 1425m, 1351m, 1322w, 1301w, 1271w, 1060s, 970m, 8 7w2, 758s, 68 w7. 1H-NMR
((D6)DMSO): 9.70 (br. s, NH2); 7.68( d-like, 1 arom. H); 7.44 (t-like, 1 arom. H); 7.35 (d-like, 1 arom. H);
7.25 (t-like, 1 arom. H); 3.48( s, MeN); 2.07 1.71 (m, 6 CH2). 13C-NMR ((D6)DMSO): 176.0 (s, CˆN); 141.4,
136.2 (2s, 2 arom. C); 128.4, 124.8, 123.7, 110.9 (4d, 4 arom. CH); 53.6 (s, C(3)); 36.3, 29.2, 22.9 (3t, 6 CH2); 29.4
‡
(q, MeN). CI-MS: 230 (16), 229 (100, [M À BF4] ), 218(28), 108(21). Anal. calc. for C 15H21BF4N2 (316.15): C
56.99, H 6.70, N 8.86; found: C 56.78, H 6.66, N 8.63.
5.7. 2-Amino-5-methoxy-1,3,3-trimethyl-3H-indolium Tetrafluoroborate (14g). According to GP 2, with 1g
(628mg, 3.07 mmol), THF (80ml), and BF 3 ¥ OEt2 (0.92 ml, 3.52 mmol). Filtration and washing of the
precipitate with Et2O yielded 379 mg (42%) of 14g. White solid, which was recrystallized from EtOH to give
colorless crystals. M.p. 253.8 254.2 8. IR (KBr): 3386s, 3316m, 3251s, 3218s, 3008m, 2844w, 1688s, 1612s, 1504s,
1484s, 1463s, 1447m, 1291s, 1255m, 1217s, 1028s, 8 8 m4 , 8 20s, 767w, 656m. 1H-NMR ((D6)DMSO): 9.89, 9.57 (2
br. s, 2 NH); 7.30 7.18( m, 2 arom. H); 7.00 6.92 (m, 1 arom. H); 3.76 (s, MeO); 3.47 (s, MeN); 1.51 (s, 2 Me).
13C-NMR ((D6)DMSO): 175.0 (s, CˆN); 157.4, 137.5, 134.8(3 s, 3 arom. C); 113.0, 111.4, 109.4 (3d, 3 arom. CH);
‡
55.7 (q, MeO); 47.1 (s, C(3)); 29.4 (q, MeN); 24.1 (q, 2 Me). CI-MS: 410 (11, [2 M À BF4] ), 409 (40, [2 M À
‡
‡
BF4 À 1] ), 206 (14), 205 (100, [M À BF4] ). Anal. calc. for C12H17BF4N2O (292.08): C 49.35, H 5.87, N 9.59;
found: C 49.45, H 5.81, N 9.61.
5.8. 2-Amino-1,3,3-trimethyl-5-nitro-3H-indolium Tetrafluoroborate (14h). According to GP 2, with 1h
(1.85 g, 8.44 mmol), THF (185 ml), and BF3 ¥ OEt2 (2.463 ml, 9.41 mmol). Filtration and washing of the
precipitate with Et2O yielded 681 mg (26%) of 14h. Pale yellow solid. M.p. 211 2138. IR (KBr): 3366m, 3222s,
3114m, 3081m, 2997m, 1690s, 1641s, 1592s, 1522s, 1387s, 1347s, 1297m, 1246m, 1193m, 1061s, 916s, 8 73m, 8 55m,
833w, 78 9w, 756w, 723w, 705m. 1H-NMR ((D6)DMSO): 8.34 (d-like, 1 arom. H); 8.18 (br. s, 1 arom. H); 7.71 (d-
like, 1 arom. H); 3.32 (s, MeN); 1.37 (s, 2 Me). 13C-NMR ((D6)-DMSO): 170.1 (s, CˆN); 148.8, 146.6, 137.3 (3s,
3 arom. C); 129.6, 124.8, 111.3 (3d, 3 arom. CH); 58.2 (s, C(3)); 40.0 (q, MeN); 23.9 (q, 2 Me). CI-MS: 238(100),
‡
222 (9), 221 (9), 220 (71, [M À BF4] ), 190 (7).
6. Reaction of 3H-Indolium Tetrafluoroborates 14 with NaOH. General Procedure 3 (GP 3). A soln. of 14 in
the least amount of H2O was cooled to 08, and aq. NaOH (30%) was added. The cooled mixture (ice bath) was
stirred for 25 min to 2 h. After extraction with CH2Cl2, the org. phase was washed with brine and dried
(Na2SO4). Evaporation of the solvent gave 15.
6.1. 3-Benzyl-1,3-dihydro-2-imino-1,3-dimethyl-2H-indole Hydrate (15a). According to GP 3, with 14a
(328mg, 0.70 mmol), 30% aq. NaOH (3.5 ml), stirring for 2 h. Yield: 248mg (95%) of 15a. Pale yellow, viscous
oil. IR (film): 3304m, 3058m, 3030m, 2963m, 2924m, 1645s, 1608s, 1573s, 1496s, 1468s, 1452s, 1389s, 1363m,
1308m, 1265w, 1227m, 1191m, 1157w, 1122m, 1097s, 1075w, 1055w, 1031w, 1020m, 995s, 922w, 8 56w, 749s, 699s,

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663w, 622w. 1H-NMR: 7.17 7.00 (m, 6 arom. H); 6.90 6.81 (m, 3 arom. H); 3.00 (s, MeN); 2.93 (s, PhCH2); 1.42
(s, Me). 13C-NMR: 174.8( s, CˆN); 145.0, 135.9, 133.3 (s, 3 arom. C); 130.0, 129.8, 128.1, 128.0, 127.8, 126.4,
122.9, 120.2, 106.4 (9d, 9 arom. CH); 49.7 (s, C(3)); 46.6 (t, PhCH2); 26.6 (q, MeN); 24.4 (q, Me). CI-MS: 252
‡
(18), 251 (100, [M ‡ 1 À H2O] ).
6.2. 1,3-Dihydro-2-imino-1,3-dimethyl-3-(2-methylpropyl)-2H-indole Hydrate (15b). According to GP 3,
with 14b (25 mg, 0.08 mmol), 30% aq. NaOH (2.5 ml), stirring for 25 min. Yield: 17 mg (88%) of 15b. Colorless
viscous oil. IR (film): 3305m, 3054m, 2958s, 2870m, 1647s, 1608s, 1496s, 1468s, 1388m, 1363m, 1309m, 1262m,
1210m, 1125s, 1086m, 1046m, 1020m, 999m, 978m, 918w, 746s, 699w, 622w. 1H-NMR: 7.16 (t-like, 1 arom. H); 7.03
(d-like, 1 arom. H); 6.89 (t-like, 1 arom. H); 6.70 (d-like, 1 arom. H); 5.55 (br. s, NH); 3.27 (s, MeN); 1.79 1.71
(m, CH2); 1.28( s, Me); 1.22 1.12 (m, CH); 0.60, 0.47 (2d-like, J ˆ 6.7, 2 Me). 13C-NMR: 176.1 (s, CˆN); 144.7,
134.4 (2s, 2 arom. C); 127.7, 122.5, 121.1, 107.1 (4d, 4 arom. CH); 48.8 (s, C(3)); 48.3 (t, CH2); 28.1 (q, MeN); 27.5
.
‡
(q, Me); 25.4 (d, CH); 23.8, 23.3 (2q, 2 Me). GC/EI-MS: 216 (11, [M À H2O] ), 173 (19), 160 (100), 159 (77),
144 (12), 130 (9), 117 (12), 77 (5). Anal. calc. for C14H22N2O (234.34): C 71.76, H 9.46, N 11.95; found: C 72.00,
H 9.29, N 11.76.
6.3. 1',3'-Dihydro-2'-imino-1'-methylspiro[cyclobutane-1,3'-[2H]indole] Hydrate (15c). According to GP 3,
with 14c (100 mg, 0.36 mmol), 30% aq. NaOH (10 ml), stirring for 2 h. Yield: 70 mg (94%) of 15c. Pale yellow
viscous oil. IR (film): 3302m, 2948s, 1651s, 1600s, 1494s, 1388s, 1345s, 1273s, 1230s, 1160s, 1125s, 1054m, 1020m,
983s, 8 47m, 748s, 701s, 605w. 1H-NMR ((D6)DMSO): 7.33 (t-like, 2 arom. H); 7.08( t-like, 1 arom. H); 6.92 (d-
like, 1 arom. H); 3.20 (s, MeN); 2.33 2.21 (m, 2 H); 2.05 1.88 (m, 1 H); 1.82 1.70 (m, 2 H); 1.50 1.35 (m,
1 H). 13C-NMR ((D6)DMSO): 168.1 (s, CˆN); 148.5 (s, 1 arom. C); 129.2, 123.3, 122.2 (3d, 4 arom. CH); 63.7 (s,
‡
C(3)); 42.3 (q, MeN); 37.0 (t, 2 CH2); 15.4 (t, CH2). CI-MS: 188 (18), 187 (100, [M ‡ 1 À H2O] ).
6.4. 1',3'-Dihydro-2'-imino-1'-methylspiro[cyclopentane-1,3'-[2H]indole] Hydrate (15d). According to
GP 3, with 14d (50 mg, 0.17 mmol), 30% aq. NaOH (5 ml), stirring for 2 h. CC (MeOH/CH2Cl2 1.5 :10)
yielded 35 mg (92%) of 15d. Colorless viscous oil. IR (film): 3302m, 3053m, 2955s, 2870m, 1645s, 1607s, 1495s,
1467s, 1428m, 1387s, 1362m, 1301m, 1272w, 1216m, 1179w, 1158w, 1141m, 1124m, 1097m, 1065m, 1022m, 962s,
922w, 8 49w, 743s, 693w. 1H-NMR ((D6)DMSO): 7.20 7.15 (m, 2 arom. H); 6.87 (t-like, 1 arom. H); 6.82 (d-like,
1 arom. H); 3.65 (br. s, NH); 3.14 (s, MeN); 2.02 1.85, 1.81 1.67 (m, 4 CH2). 1H-NMR: 7.13 (t-like, 1 arom. H);
7.07 (d-like, 1 arom. H); 6.85 (t-like, 1 arom. H); 6.63 (d-like, 1 arom. H); 5.07 (br. s, NH); 3.18( s, MeN); 2.00
1.82 (2m, 4 CH2). 13C-NMR ((D6)DMSO): 174.9 (s, CˆN); 144.3, 137.0 (2s, 2 arom. C); 127.3, 121.8, 120.4, 106.5
(4d, 4 arom. CH); 53.8( s, C(3)); 40.3, 25.7 (2t, 4 CH2); 26.8( q, MeN). 13C-NMR: 177.8( s, CˆN); 144.5, 137.4
(2s, 2 arom. C); 127.4, 121.9, 120.8, 106.5 (4d, 4 arom. CH); 54.7 (s, C(3)); 41.0, 26.5 (2t, 4 CH2); 26.5 (q, MeN).
.
‡
‡
GC/EI-MS: 201 (2, [M ‡ 1 À H2O] ), 200 (14, [M À H2O] ), 160 (13), 159 (100), 144 (6).
6.5. 1',3'-Dihydro-2'-imino-1'-methylspiro[cyclohexane-1,3'-[2H]indole] Hydrate (15e). According to GP 3,
with 14e (64 mg, 0.21 mmol), 30% aq. NaOH (6.4 ml), stirring for 2 h. Yield: 47 mg (96%) of 15e. Colorless oil,
which solidified at 08. IR (KBr): 3278s, 3055m, 2931s, 2854s, 1635s, 1603s, 1496s, 1466s, 1449s, 1393s, 1364m,
1311s, 1298m, 1228s, 1187m, 1159m, 1124s, 1074m, 1028m, 995s, 935m, 916m, 8 53m, 8 17m, 793m, 759m, 742s,
693m, 674w. 1H-NMR ((D6)DMSO): 7.73 (d-like, 1 arom. H); 7.42 (t-like, 1 arom. H); 7.11 7.02 (m, 2 arom. H);
3.32 (s, MeN); 2.07 1.87, 1.80 1.54 (2m, 5 CH2). 13C-NMR ((D6)DMSO): 173.8( s, CˆN); 144.6, 134.7 (2s, 2
arom. C); 127.3, 124.0, 119.4, 106.5 (4d, 4 arom. CH); 46.9 (s, C(3)); 34.6, 24.5, 20.8(3 t, 5 CH2); 26.6 (q, MeN).
‡
CI-MS: 216 (16), 215 (100, [M ‡ 1 À H2O] ).
6.6. 1',3'-Dihydro-2'-imino-1'-methylspiro[cycloheptane-1,3'-[2H]indole] Hydrate (15f). According to
GP 3, with 14f (60 mg, 0.19 mmol), 30% aq. NaOH (6.0 ml), stirring for 2 h. Yield: 45 mg (96%) of 15f. Pale
yellow viscous oil. IR (film): 3323m, 3051m, 2923s, 2852s, 1644s, 1604s, 1494s, 1464s, 1386s, 1358m, 1307m,
1264m, 1216m, 1160m, 1123m, 1081m, 1045m, 1025m, 1008m, 990s, 961w, 741s, 690m. 1H-NMR ((D6)DMSO):
7.32 (d-like, 1 arom. H); 7.16 (t-like, 1 arom. H); 6.85 (t-like, 1 arom. H); 6.78( d-like, 1 arom. H); 3.09 (s, MeN);
1.90 1.55 (m, 6 CH2). 13C-NMR ((D6)DMSO): 175.2 (s, CˆN); 144.2, 137.0 (2s, 2 arom. C); 127.3, 122.4, 119.8,
106.5 (4d, 4 arom. CH); 50.0 (s, C(3)); 26.5 (q, MeN); 38.7, 30.5, 23.2 (3t, 6 CH2). CI-MS: 230 (17, [M À OH ‡
.
‡
‡
‡
1] ), 229 (100, [M À OH] or [M À NH3] ).
6.7. 1,3-Dihydro-2-imino-5-methoxy-1,3,3-trimethyl-2H-indole Hydrate (15g). According to GP 3, with 14g
(61.5 mg, 0.21 mmol), 30 % aq. NaOH (6 ml), stirring for 2 h. Yield: 46.5 mg (99%) of 15g. Colorless viscous oil.
IR (film): 3304m, 3035m, 2963s, 2929s, 2865m, 2834m, 1645s, 1599s, 1503s, 1471s, 1437s, 1388s, 1363m, 1290s,
1242s, 1213s, 1182m, 1114s, 1068m, 1032s, 1005s, 946m, 909w, 8 74m, 8 53s, 8 01s, 715w, 695m, 615w, 603m.
1H-NMR ((D6)DMSO): 6.91 6.89, 6.78 6.68 (2m, 3 arom. H); 3.70 (s, MeO); 3.09 (s, MeN); 1.27 (s, 2 Me).
13C-NMR ((D6)DMSO): 174.7 (s, CˆN); 154.1, 138.3, 137.1 (3s, 3 arom. C); 111.7, 109.8, 106.5 (3d, 3 arom. CH);
‡
55.5 (q, MeO); 44.0 (s, C(3)); 26.6 (q, MeN); 26.2 (q, 2 Me). CI-MS: 206 (15), 205 (100, [M ‡ 1 À H2O] ).

Helvetica Chimica Acta Vol. 87 (2004)
2399
7. Reaction of 3H-Indolium Tetrafluoroborates 14 with Ac2O/Pyridine. General Procedure 4 (GP 4). A soln.
of 14 in pyridine/Ac2O 1:1 (v/v) was stirred at ca. 238 for 16 h. Then, the solvent was evaporated, and the residue
was dissolved in CHCl3, washed with H2O and brine, and dried (Na2SO4). After filtration, evaporation, and CC
with the proper solvent mixture, two products 16 and 17 were isolated.
7.1. N-(3-Benzyl-1,3-dihydro-1,3-dimethyl-2H-indol-2-yliden)acetamide (16a) and 3-Benzyl-1,3-dihydro-
1,3-dimethyl-2H-indol-2-one (17a). According to GP 4, with 14a (647 mg, 1.91 mmol), pyridine/Ac2O (6.5 ml
each), CC (Et2O/hexane 2 :5). The two products were purified by means of HPLC (AcOEt/hexane 2 :10, 0.5 ml/
min, 13 atm). Crystallization of the main product from hexane yielded 233 mg (42%) of 16a. Colorless prisms.
M.p. 99.78. Crystals suitable for an X-ray crystal-structure determination were grown from hexane. IR (KBr):
3052w, 2964w, 2926w, 1669s, 1639s, 1603s, 1494s, 1470m, 1379m, 1354m, 1288m, 1224s, 1209m, 1199s, 1154w,
1125m, 1102m, 1079w, 1062m, 1025w, 998w, 952m, 943m, 8 07w, 764m, 748m, 710s, 675w, 650w, 602m. 1H-NMR:
7.21 6.98( m, 6 arom. H); 6.91 6.84 (m, 2 arom. H); 6.54 (d-like, 1 arom. H); 3.53, 3.01 (AB, J ˆ 12.7, PhCH2);
2.89 (s, MeN); 2.33 (s, MeCO); 1.58( s, Me). 13C-NMR: 181.7 (s, CˆO); 165.1 (s, CˆN); 143.7, 136.2, 134.2 (3s, 3
arom. C); 129.7, 127.8, 127.2, 126.2, 122.5, 121.8, 107.5 (7d, 9 arom. CH); 52.3 (s, C(3)); 46.8( t, PhCH2); 28.1, 27.5
‡
(2q, MeCO, MeN); 22.4 (q, Me). CI-MS: 294 (16), 293 (100, [M ‡ 1] ). Anal. calc. for C19H20N2O (292.37): C
78.05, H 6.89, N 9.58; found: C 78.07, H 7.04, N 9.57.
As a minor product, 79 mg (16%) of 17a was obtained. Crystallization from hexane gave colorless prisms
suitable for an X-ray crystal-structure determination. M.p. 96.58 ([42]: 89 948). IR (KBr): 3058w, 3029w,
2971m, 2922m, 1703s, 1613s, 1496s, 1473m, 1449s, 1422w, 1377s, 1350m, 1266m, 1245w, 1124m, 1103m, 1086w,
1053w, 1026m, 941w, 913w, 757s, 738m, 701s, 604w. 1H-NMR: 7.21 7.02 (m, 6 arom. H); 6.88 6.83 (m, 2 arom.
H); 6.64 6.59 (d-like, 1 arom. H); 3.11, 3.00 (AB, J ˆ 13, PhCH2); 2.98( s, MeN); 1.48( s, Me). 13C-NMR: 179.8
(s, CˆO); 143.1, 136.1, 132.9 (3s, 3 arom. C); 129.7, 127.6, 127.4, 126.3, 123.2, 121.9, 107.6 (7d, 9 arom. CH); 49.8
‡
(s, C(3)); 44.5 (t, PhCH2); 25.7 (q, MeN); 22.6 (q, Me). CI-MS: 270 (5), 269 (32, [M ‡ NH4] ), 253 (18), 252
‡
(100, [M ‡ 1] ). Anal. calc. for C17H17NO (251.32): C 81.24, H 6.82, N 5.57; found: C 81.29, H 6.70, N 5.56.
7.2. N-[1,3-Dihydro-1,3-dimethyl-3-(2-methylpropyl)-2H-indol-2-yliden]acetamide (16b) and 1,3-Dihydro-
1,3-dimethyl-3-(2-methylpropyl)-2H-indol-2-one (17b). According to GP 4, with 14b (300 mg, 0.99 mmol),
pyridine/Ac2O (3 ml each). CC (Et2O/hexane 3 :10) yielded 863 mg (34%) of 16b. Colorless oil. IR (film):
3055w, 2957s, 2928s, 2870m, 1651s, 1603s, 1493s, 1470s, 1432s, 1378s, 1352s, 1290s, 1211s, 1158m, 1133s, 1091s,
1061w, 1021m, 999m, 978m, 944s, 8 8 w5, 8 55w, 8 04w, 749s, 716w, 654m, 600s. 1H-NMR: 7.45 (t-like, 1 arom. H);
7.30 (d-like, 1 arom. H); 7.22 (t-like, 1 arom. H); 7.00 (d-like, 1 arom. H); 3.41 (s, MeN); 2.49 (s, MeCO); 2.32
2.22, 1.99 1.90 (2m, CH2); 1.68( s, Me); 1.61 1.44 (m, CH); 0.96, 0.70 (2d, 2 Me). 13C-NMR: 181.1 (s, CˆO);
165.6 (s, CˆN); 143.6, 135.6 (2s, 2 arom. C); 127.6, 122.2, 122.0, 107.8(4 d, 4 arom. CH); 50.6 (s, C(3)); 47.7 (t,
.
‡
CH2); 28.6, 27.3 (2q, MeCO, MeN); 27.6 (q, Me); 25.7 (d, CH); 23.5, 23.2 (2q, 2 Me). EI-MS: 258(13, M ), 243
(8), 215 (35), 202 (88), 187 (7), 173 (30), 160 (100), 159 (70), 158 (12), 144 (17), 132 (10), 117 (12). Anal. calc.
for C16H22N2O (258.36): C 74.38, H 8.58, N 10.84; found: C 74.10, H 8.71, N 10.61.
As a minor product, 34 mg (16%) of 17b was obtained. Colorless oil. IR (film): 3055m, 2958s, 2870s, 1719s,
1613s, 1493s, 1471s, 1452s, 1423m, 1377s, 1347s, 1309m, 1250m, 1174m, 1157w, 1126s, 1086s, 1050m, 1024s, 98 1w,
920w, 753s, 741s, 699m, 640w. 1H-NMR: 7.28( t-like, 1 arom. H); 7.15 (d-like, 1 arom. H); 7.07 (t-like, 1 arom. H);
6.85 (d-like, 1 arom. H); 3.22 (s, MeN); 2.00 1.92, 1.80 1.72 (2m, CH2); 1.32 (s, Me); 1.31 1.18( m, CH); 0.65,
0.61 (2d, 2 Me). 13C-NMR: 180.9 (s, CˆO); 143.1, 134.1 (2s, 2 arom. C); 127.4, 122.7, 122.2, 107.8(4 d, 4 arom.
CH); 47.9 (s, C(3)); 46.7 (t, CH2); 26.0 (q, MeN); 25.4 (d, CH); 24.0 (q, Me); 22.7 (q, 2 Me). GC/EI-MS: 217 (10,
.
‡
M
), 162 (11), 161 (100), 160 (57), 130 (13), 117 (10). Anal. calc. for C14H19NO (217.31): C 77.38, H 8.81, N
6.45; found: C 77.08, H 8.76, N 6.41.
7.3. N-(1',3'-Dihydro-1'-methylspiro[cyclobutane-1,3'-[2H]indol]-2'-yliden)acetamide (16c) and 1',3'-Dihy-
dro-1'-methylspiro[cyclobutane-1,3'-[2H]indol]-2'-one (17c). According to GP 4, with 14c (200 mg, 0.73 mmol),
pyridine/Ac2O (2 ml each). CC (Et2O/hexane 2 :5) yielded 73 mg (53%) of 17c. Colorless oil. The acetamide
16c could not be isolated, but was identified by EI-GC/MS.
Data of 17c: IR (film): 3567w, 3055m, 2987m, 2936s, 2884m, 1713s, 1614s, 1493s, 1470s, 1423m, 1375s, 1349s,
1
1313m, 1273m, 1250m, 1165m, 1120m, 1100s, 1062m, 1007m, 942w, 750s, 698m. H-NMR: 7.53 7.47 (d-like, 1
arom. H); 7.30 7.22 (t-like, 1 arom. H); 7.12 7.05 (t-like, 1 arom. H); 6.8 6.76 ( d-like, 1 arom. H); 3.19 (s,
MeN); 2.70 2.61 (m, CH2); 2.41 2.24 (m, 2 CH2). 13C-NMR: 180.1 (s, CˆO); 142.9, 134.3 (2s, 2 arom. C);
127.7, 122.4, 122.1, 107.5 (4d, 4 arom. CH); 48.0 (s, C(3)); 31.2 (t, 2 CH2); 26.0 (q, MeN); 16.6 (t, CH2). GC/EI-
.
‡
MS: 188 (3), 187 (33, M ), 160 (10), 159 (100), 131 (24), 130 (39), 115 (4), 103 (7), 89 (9), 77 (10). Anal. calc.
for C12H13NO (187.24): C 76.98, H 7.00, N 7.48; found: C 76.91, H 7.03, N 7.46.
7.4. N-(1',3'-Dihydro-1'-methylspiro[cyclopentane-1,3'-[2H]indol]-2'-yliden)acetamide (16d) and 1',3'-Di-
hydro-1'-methylspiro[cyclopentane-1,3'-[2H]indol]-2'-one (17d). According to GP 4, with 14d (200 mg,

2400
Helvetica Chimica Acta Vol. 87 (2004)
0.69 mmol), pyridine/Ac2O (2 ml each). CC (AcOEt/hexane 1:5) yielded 84 mg (50%) of 16d. Colorless oil. IR
(film): 3054w, 2955s, 2871m, 1711s, 1651s, 1604s, 1492s, 1470s, 1428m, 1376s, 1352s, 1292m, 1281m, 1211s, 1170m,
1126m, 1086s, 1023m, 965s, 925w, 8 53w, 8 00w, 746s, 697w, 655w, 600m. 1H-NMR: 7.28 7.15 ( m, 2 arom. H); 7.03
(t-like, 1 arom. H); 6.80 (d-like, 1 arom. H); 3.20 (s, MeN); 2.43 2.32, 2.09 1.80 (2m, 4 CH2); 2.28( s, MeCO).
13C-NMR: 180.8 (s, CˆO); 167.3 (s, CˆN); 142.9, 138.9 (2s, 2 arom. C); 127.3, 122.4, 121.8, 107.7 (4d, 4 arom.
.
‡
CH); 56.1 (s, C(3)); 39.8, 26.6 (2t, 4 CH2); 29.2, 27.3 (2q, MeCO, MeN). GC/EI-MS: 243 (3), 242 (23, M ), 227
(11), 214 (22), 202 (8), 201 (79), 160 (100), 159 (60), 130 (38), 115 (13).
As a minor product, 57 mg (41%) of 17d was obtained. Colorless oil, which solidified in h.v. to give a white
solid. M.p. 58.78 ([43]: 58 59 8). IR (KBr): 3054w, 2955m, 2870w, 1711s, 1613s, 1493s, 1470s, 1421w, 1376s, 1348s,
1317w, 1301w, 1264w, 1159w, 1124m, 1094w, 1078m, 1021w, 969w, 746m, 697w. 1H-NMR: 7.28 7.15 ( m, 1 arom.
H); 7.04 (t-like, 1 arom. H); 6.81 (d-like, 1 arom. H); 3.20 (s, MeN); 2.21 1.92, 1.87 1.78 (2m, 4 CH2).
13C-NMR: 181.8 (s, CˆO); 142.8, 136.7 (2s, 2 arom. C); 127.2, 122.4, 122.1, 107.6 (4d, 4 arom. CH); 53.8( s, C(3));
.
‡
38.2, 26.5 (2t, 4 CH2); 26.1 (q, MeN). GC/EI-MS: 202 (4), 201 (33, M ), 161 (12), 160 (100), 159 (13), 144 (6),
130 (17). Anal. calc. for C13H15NO (201.27): C 77.58, H 7.51, N 6.96; found: C 77.28, H 7.28, N 6.92.
7.5. N-(1',3'-Dihydro-1'-methylspiro[cyclohexane-1,3'-[2H]indol]-2-yliden)acetamide (13e) and 1',3'-Dihy-
dro-1'-methylspiro[cyclohexane-1,3'-[2H]indol]-2'-one (17e). According to GP 4, with 14e (152 mg,
0.50 mmol), pyridine/Ac2O (1.5 ml each). CC (AcOEt/hexane 1:2) yielded 73 mg (57%) of 16e. Slightly
yellow oil. IR (film): 3054w, 2934s, 2866m, 1711 1652s (br.), 1604s 1490s, 1470s, 1376s, 1353s, 1302m, 1283s,
1217s, 1161w, 1144w, 1126m, 1100m, 1085s, 1029m, 993m, 939s, 908w, 8 61w, 746s, 694m, 600m. 1H-NMR: 7.56 (d-
like, 1 arom. H); 7.29 (t-like, 1 arom. H); 7.02 (t-like, 1 arom. H); 6.85 (d-like, 1 arom. H); 3.17 (s, MeN); 2.28( s,
MeCO); 2.10 1.97, 1.89 1.75, 1.67 1.57 (3m, 5 CH2). 13C-NMR: 180.1 (s, CˆO); 165.6 (s, CˆN); 143.5, 135.8
(2s, 2 arom. C); 127.5, 124.4, 121.7, 108.1 (4d, 4 arom. CH); 49.9 (s, C(3)); 33.7, 24.7, 21.1 (3t, 5 CH2); 29.7, 27.3
‡
(2q, MeCO, MeN). CI-MS: 258(18), 257 (100, [ M ‡ 1] ), 216 (34).
As a minor product, 57 mg (32%) of 17e was obtained. Colorless viscous oil (cf. [44]). IR (film): 3054w,
2933s, 2854s, 1712s, 1645m, 1612s, 1493s, 1470s, 1449s, 1421m, 1377s, 1351s, 1313m, 1295m, 1252s, 1161m, 1144m,
1122m, 1092m, 1081m, 1066m, 1027m, 1007m, 935m, 912w, 8 57w, 757s, 745s, 694m. 1H-NMR: 7.45 (d-like, 1
arom. H); 7.30 (t-like, 1 arom. H); 7.07 (t-like, 1 arom. H); 6.85 (d-like, 1 arom. H); 3.21 (s, MeN); 2.01 1.51 (m,
5 CH2). 13C-NMR: 180.6 (s, CˆO); 142.7, 135.3 (2s, 2 arom. C); 127.3, 123.7, 121.8, 107.7 (4d, 4 arom. CH); 47.4 (s,
.
‡
‡
C(3)); 32.9, 25.1, 21.1 (3t, 5 CH2); 26.0 (q, MeN). CI-MS: 217 (16), 216 (100, [M ‡ 1] ), 215 (12, M ).
The reaction described above was also carried out with hydrate 15e as the starting material: 15e (144 mg,
0.62 mmol), pyridine/Ac2O (1.5 ml each). CC (AcOEt/hexane 1:2) yielded 98.5 mg (62%) of 16e and 21.6 mg
(16%) of 17e.
7.6. N-(1',3'-Dihydro-1'-methylspiro[cycloheptane-1,3'-[2H]indol]-2'-yliden)acetamide (16f) and 1',3'-Dihy-
dro-1'-methylspiro[cycloheptane-1,3'-[2H]indol]-2'-one (17f). According to GP 4, with 14f (110 mg,
0.35 mmol), pyridine/Ac2O (1.1 ml each). CC (AcOEt/hexane 1:2) yielded 45 mg (48%) of 16f. Slightly
yellow oil. IR (film): 3054m, 2923s, 2855s, 1711 1651s (br.), 1604s 1490s, 1463s, 1351s, 1292s, 1275s, 1245s, 1212s,
1167m, 1130m, 1113m, 1092s, 1028m, 1013m, 992m, 963s, 915m, 8 92m, 8 56w, 8 03w, 744s, 723m, 693m, 651w, 600s.
1H-NMR: 7.38( d-like, 1 arom. H); 7.25 (t-like, 1 arom. H); 7.05 (t-like, 1 arom. H); 6.81 (d-like, 1 arom. H); 3.15
(s, MeN); 2.28( s, MeCO); 2.19 2.05, 1.98 1.83, 1.82 1.58 (3m, 6 CH2). 13C-NMR: 180.1 (s, CˆO); 165.5 (s,
CˆN); 143.2, 137.9 (2s, 2 arom. C); 127.5, 123.1, 122.3, 108.0 (4d, 4 arom. CH); 52.5 (s, C(3)); 30.0, 27.1 (2q,
‡
MeCO, MeN); 38.1, 31.0, 24.0 (3t, 6 CH2). CI-MS: 272 (16), 271 (100, [M ‡ 1] ), 230 (27), 210 (23), 196 (15),
134 (5), 122 (9).
As a minor product, 24.5 mg (31%) of 17f was obtained. Colorless oil. IR (film): 3054m, 2923s, 2854s, 1714s,
1612s, 1494s, 1471s, 1420m, 1377s, 1346s, 1307m, 1282w, 1258s, 1238m, 1170m, 1125s, 1112m, 1082s, 1025m,
1012m, 965s, 926w, 904w, 8 8 w3, 8 57w, 744s, 693m, 652w. 1H-NMR: 7.35 (d-like, 1 arom. H); 7.25 (t-like, 1 arom.
H); 7.04 (t-like, 1 arom. H); 6.81 (d-like, 1 arom. H); 3.18( s, MeN); 2.05 1.91, 1.83 1.65 (2m, 6 CH2).
13C-NMR: 182.3 (s, CˆO); 142.5, 137.3 (2s, 2 arom. C); 127.2, 122.6, 122.2, 107.7 (4d, 4 arom. CH); 50.0 (s, C(3));
‡
36.8, 31.1, 23.7 (3t, 6 CH2); 26.0 (q, MeN). CI-MS: 231 (16), 230 (100, [M ‡ 1] ).
7.7. N-(1,3-Dihydro-5-methoxy-1,3,3-trimethyl-2H-indol-2-yliden)acetamide (16g) and 1,3-Dihydro-5-
methoxy-1,3,3-trimethyl-2H-indole-2-one (17g). According to GP 4, with 14g (151.5 mg, 0.52 mmol), pyridine/
Ac2O (1.5 ml each). CC (AcOEt/hexane 3.5 :10) yielded 30.2 mg (24%) of 16g. Pale yellow oil. IR (film): 2968s,
2931s, 2836m, 1709s, 1650s, 1502s, 1437s, 1383s, 1356s, 1305s, 1281s, 1213s, 1125s, 1058s, 1028s, 1002m, 949s, 925m,
1
909m, 8 78s, 8 03s, 729s, 692w, 645w, 627w, 600m. H-NMR: 6.83 6.69 (m, 3 arom. H); 3.81 (s, MeO); 3.20 (s,
MeN); 2.28( s, MeCO); 1.51 (s, 2 Me). 13C-NMR: 181.0 (s, CˆO); 165.2 (s, CˆN); 156.0, 138.6, 136.2 (3s, 3
arom. C); 111.8, 109.3, 108.1 (3d, 3 arom. CH); 55.7 (q, MeO); 47.2 (s, C(3)); 28.7, 27.3 (2q, MeCO, MeN); 25.9

Helvetica Chimica Acta Vol. 87 (2004)
2401
‡
(q, 2 Me). CI-MS: 247 (19, [M ‡ 1] ), 206 (100), 77 (19). Anal. calc. for C14H18N2O2 (246.30): C 68.27, H 7.37, N
11.37; found: C 68.12, H 7.36, N 11.21.
As a second product, 41.1 mg (39%) of 17g was obtained. Colorless viscous oil. (cf. [44]). IR (film): 3061m,
2967s, 2835m, 1714s, 1603s, 1494s, 1383s, 1355s, 1290s, 1246s, 1217s, 1180s, 1120s, 1067s, 1049s, 1028s, 946m, 8 8 2s,
869m, 8 05s, 754w, 744m, 729m, 697s, 624m, 612m. 1H-NMR: 6.95 6.70 (m, 3 arom. H); 3.80 (s, MeO); 3.20 (s,
MeN); 1.36 (s, 2 Me). 13C-NMR: 181.0 (s, CˆO); 156.1, 137.3, 136.2 (3s, 3 arom. C); 111.7, 110.1, 108.2 (3d, 3
‡
arom. CH); 55.9 (q, MeO); 44.6 (s, C(3)); 26.3 (q, MeN); 24.4 (q, 2 Me). CI-MS: 411 (17, [2 M ‡ 1] ), 207 (14),
.
‡
‡
206 (100, [M ‡ 1] ), 205 (13, M ). Anal. calc. for C12H15NO2 (205.25): C 70.22, H 7.37, N 6.82; found: C 70.06, H
7.39, N 6.84.
7.8. N- (1,3-Dihydro-1,3,3-trimethyl-5-nitro-2H-indol-2-yliden)acetamide (16h) and 1,3-dihydro-1,3,3-tri-
methyl-5-nitro-2H-indole-2-one (17h). According to GP 4, with 14h (172.2 mg, 0.56 mmol), pyridine/Ac2O
(1.7 ml each). CC (AcOEt/hexane 1:2) yielded 42.8mg (29%) of 16h. Yellow powder. M.p. 136.4 138.28. IR
(KBr): 3086w, 2968w, 2929m, 1729m, 1695s, 1658s, 1610s, 1498s, 1466m, 1439m, 1390m, 1332s, 1263s, 1202s, 1123s,
1058s, 1031m, 1002m, 949s, 8 8 5w, 8 35w, 8 25m, 797m, 758m, 737m, 703w, 677m. 1H-NMR: 8.22, 8.01, 6.85 (3d-like,
3 arom. H); 3.26 (s, MeN); 2.32 (s, MeCO); 1.58( s, 2 Me). 13C-NMR: 181.7 (s, CˆO); 163.8( s, CˆN); 148.7,
142.8, 137.4 (3s, 3 arom. C); 125.4, 117.6, 107.0 (3d, 3 arom. CH); 46.4 (s, C(3)); 28.3, 27.2 (2q, MeCO, MeN); 25.7
.
‡
‡
(q, 2 Me). CI-MS: 263 (15), 262 (100, [M ‡ 1] ), 238(12), 232 (26), 210 (12). EI-MS: 261 (47, M ), 246 (100),
231 (18), 218 (12), 204 (24).
As a minor product, 6.4 mg (5%) of 17h was obtained. Yellow solid. M.p. 202.3 203.38 ([45]: 204 2058).
IR (KBr): 3109w, 2977w, 2928w, 1725s, 1615s, 1509s, 1492s, 1463m, 1434w, 1416m, 1390m, 1378m, 1351s, 1332s,
1295s, 1266m, 1237m, 1195w, 1132m, 1119s, 1104m, 1049m, 1040s, 942m, 8 95m, 8 36m, 794w, 757m, 737w, 710w,
662w. 1H-NMR: 8.25, 8.09, 6.92 (3d-like, 3 arom. H); 3.28( s, MeN); 1.44 (s, 2 Me). 13C-NMR: 181.3 (s, CˆO);
148.4, 143.8, 136.5 (3s, 3 arom. C); 125.2, 118.3, 107.6 (3d, 3 arom. CH); 44.2 (s, C(3)); 26.7 (q, MeN); 24.2 (q, 2
.
‡
Me). GC/EI-MS: 221 (13), 220 (100, M ), 206 (10), 205 (80), 190 (10), 174 (10), 159 (37), 130 (23). CI-MS :
.
‡
‡
‡
239 (13), 238(100, [ M ‡ NH4] ), 221 (11, [M ‡ 1] ), 220 (7, M ), 192 (6), 191 (47).
8. Hydrolysis of Compounds 15 and 16. General Procedure 5 (GP 5). A soln. of 15 in H2O/THF 1:1 (v/v)
was heated to reflux for up to several days and then extracted with Et2O. The org. phase was washed with brine
and dried (Na2SO4). Evaporation of the solvent, followed by CC, gave 17. General Procedure 6 (GP 6). A soln.
of 16 in aq. HCl (10%) was either heated to reflux for 1 2 h or stirred at r.t. overnight and then extracted with
Et2O. The org. phase was washed with aq. NaHCO3 soln., and brine, and dried (Na2SO4). Evaporation of the
solvent, followed by CC, gave 17.
8.1. Hydrolysis of 15a and 16a. According to GP 5, with 15a (126 mg, 0.47 mmol) and H2O/THF (19 ml
each). Heating to reflux for 2 d yielded 109 mg (92%) of 17a. According to GP 6, with 16a (20 mg, 0.07 mmol)
and 10% aq. HCl (2 ml). Heating to reflux for 2 h gave 15.2 mg (88%) of 17a.
8.2. Hydrolysis of 15b and 16b. According to GP 5, with 15b (15 mg, 0.06 mmol) and H2O/THF (2.5 ml
each). Heating to reflux for 2 d yielded 13 mg (94%) of 17b. According to GP 6, with 16b (80 mg, 0.31 mmol)
and 10% aq. HCl (8ml). Stirring at r.t overnight. CC (Et 2O/hexane 3 :10) yielded 54 mg (80%) of 17b.
8.3. Hydrolysis of 15c. According to GP 5, with 15c (30 mg, 0.15 mmol) and H2O/THF (4.5 ml each).
Heating to reflux for 2 d yielded 23.8mg (87%) of 17c.
8.4. Hydrolysis of 15d and 16d. According to GP 5, with 15d (45 mg, 0.47 mmol) and H2O/THF (7 ml each).
Heating to reflux for 2 d yielded 39 mg (94%) of 17d. According to GP 6, with 16d (50 mg, 0.21 mmol) and 10%
aq. HCl (5 ml). Heating to reflux for 1 h yielded 39 mg (94%) of 17d.
8.5. Hydrolysis of 15e and 16e. According to GP 5, with 15e (15.5 mg, 0.07 mmol) and H2O/THF (1.5 ml
each). Heating to reflux for 3 d yielded 13 mg (91%) of 17e. According to GP 6, with 16e (50 mg, 0.20 mmol)
and 10% aq. HCl (5 ml). Heating to reflux for 1 h gave 39 mg (93%) of 17e.
8.6. Hydrolysis of 15f and 16f. According to GP 5, with 15f (16 mg, 0.07 mmol) and H2O/THF (2 ml each).
Heating to reflux for 3 d yielded 13.3 mg (89%) of 17f. According to GP 6, with 16f (20 mg, 0.07 mmol) and
10% aq. HCl (2 ml). Heating to reflux for 1 h gave 14.6 mg (86%) of 17f.
8.7. Hydrolysis of 15g and 16g. According to GP 5, with 15g (20 mg, 0.07 mmol) and H2O/THF (3 ml each).
Heating to reflux for 3 d yielded 13.34 mg (95%) of 17g. According to GP 6, with 16g (20 mg, 0.08mmol) and
10% aq. HCl (2 ml). Heating to reflux for 1 h gave 14.9 mg (89%) of 17g.
8.8. Hydrolysis of 16h. According to GP 6, with 16h (14 mg, 0.054 mmol) and 10% aq. HCl (2 ml). Heating
to reflux for 1 h yielded 4 mg (34%) of 17h.
9. Reaction of 2H-Azirin-3-amines 1g and 1h with Thiobenzoic S-Acid. General Procedure 7 (GP 7). To a
well stirred soln. of thiobenzoic S-acid (1 equiv.) in abs. MeCN at 08, a soln. of the corresponding azirine 1 (1
equiv.) in MeCN was added. The soln. was allowed to warm to r.t. and was stirred overnight. Then, the solvent

2402
Helvetica Chimica Acta Vol. 87 (2004)
was evaporated, the residue was dissolved in CH2Cl2, and the org. phase was washed with sat. NaHCO3 and
brine, and dried (Na2SO4). Pure product was obtained after CC.
9.1. N-{1,1-Dimethyl-2-[(4-methoxyphenyl)(methyl)amino]-2-thioxoethyl}benzamide (13a). With thioben-
zoic S-acid (43.5, 0.31 mmol) in 1.5 ml of MeCN and 1g (64.3 mg, 0.31 mmol) in 0.6 ml of MeCN. CC (MeOH/
CH2Cl2 0.1:10) yielded 93.1 mg (88%) of 13a. White solid. M.p. 158.2 159.38. IR (KBr): 3258s, 3061m, 3003m,
2935w, 2836w, 1637s, 1605m, 1579m, 1543s, 1501s, 1463s, 1431m, 1385s, 1369s, 1321s, 1291s, 1251s, 1213w, 1178m,
1165m, 1108s, 1096s, 1076m, 1033m, 994m, 940w, 930w, 920w, 8 44m, 8 19w, 8 04w, 760w, 724s, 695m, 670w, 635w,
621w. 1H-NMR: 7.68( AA'BB', 2 arom. H); 7.43 7.34 (m, 3 arom. H); 7.12 (AA'BB', 2 arom. H); 6.75 (d-like, 2
arom. H); 3.74 (s, MeO, MeN); 1.76 (s, 2 Me). 13C-NMR: 209.1 (s, C ˆ S); 165.0 (s, CˆO); 159.0, 139.8, 135.1 (3s,
3 arom. C); 131.1, 128.4, 127.2, 126.8, 114.4 (5d, 9 arom. CH); 62.8( s, Me2C); 55.3, 51.7 (2q, MeO, MeN); 29.0 (q,
‡
2 Me). CI-MS: 344 (36), 343 (79, [M ‡ 1] ), 289 (10), 242 (11), 222 (100), 139 (60).
9.2. N-{1,1-Dimethyl-2-[(methyl)(4-nitrophenyl)amino]-2-thioxoethyl}benzamide (13b). With thiobenzoic
S-acid (56 mg, 0.41 mmol) in 2 ml of MeCN and 8h (90 mg, 41 mmol) in 0.7 ml of MeCN. CC (AcOEt/hexane
2 :5) yielded 135 mg (92%) of 13b. Bright yellow solid. M.p. 150.5 151.38. IR (KBr): 3293m, 3104w, 3064m,
2989w, 2930w, 1642s, 1606m, 1591s, 1524s, 1489s, 1456s, 1433s, 1388s, 1346s, 1310s, 1260m, 1215m, 1172m, 1100s,
1027m, 1015m, 998w, 928w, 912w, 8 66m, 8 51m, 8 02m, 761w, 723m, 706s, 694m, 652m, 616w. 1H-NMR: 8.08, 7.55
(AA'BB', 4 arom. H); 7.45 7.35 (m, 5 arom. H); 6.62 (br. s, NH); 3.72 (s, MeN); 1.86 (s, 2 Me). 13C-NMR: 209.4
(s, C ˆ S); 165.4 (s, CˆO); 153.5, 146.5, 133.8(3 s, 3 arom. C); 131.8, 128.4, 126.9, 126.6, 124.9 (5d, 9 arom. CH);
‡
62.8( s, Me2C); 49.4 (q, MeN); 30.7 (q, 2 Me). CI-MS: 359 (23), 358(100, [ M ‡ 1] ), 342 (12), 341 (10), 340 (47),
Table 6. Crystallographic Data of Compounds 14f, 16a, and 17a
14f
16a
17a
Crystallized from
EtOH
hexane
hexane
Empirical formula
Formula weight [g molÀ1
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
C15H21BF4N2
316.15
colorless, needle
0.05 Â 0.10 Â 0.25
160(1)
C19H20N2O
292.38251.33
colorless, prism
0.28 Â 0.33 Â 0.480.25
173(1)
C17H17NO
]
colorless, prism
 0.30  0.38
173(1)
Crystal system
Space group
monoclinic
P21/n
monoclinic
P21/c
monoclinic
C2/c
Z
4
4
8
Reflections for cell determination
3649
25
25
2q Range for cell determination [8]
4
55
36 40
36 40
Unit-cell parameters a [ä]
6.5212(1)
11.7323(2)
19.8657(5)
94.1542(8)
1515.91(5)
1.385
0.115
f and w
55
9.708(2)
16.472(2)
10.947(1)
114.283(9)
1595.7(4)
1.217
0.07580.0757
w/2q
55
14.014(5)
12.895(5)
15.863(4)
108.01(2)
2726(2)
1.225
b [ä]
c [ä]
b [8]
V [ä3]
Dx [g cm3]
m(MoKa) [mmÀ1
Scan type
]
w/2q
55
2q(max) [8]
Total reflections measured
Symmetry-independent reflections
Reflections used [I > 2s(I)]
Parameters refined
30898
3479
2540
207
4012
3666
2634
200
3404
3133
1995
173
Final
R
wR
0.0491
0.0504
3.097
0.0471
0.0472
0.04580.0402
1.9681.909
2.3(1) Â 10À6
0.0002
Goodness-of-fit
Secondary extinction coefficient
Final Dmax /s
D1 (max; min) [e äÀ3
4.2(4) Â 10À7
0.0003
0.0004
0.33; À 0.26
]
0.24; À 0.280.22;
À 0.24

Helvetica Chimica Acta Vol. 87 (2004)
2403
324 (8), 323 (7), 312 (6), 311 (31), 223 (25). Anal. calc. for C18H19N3O3S (357.43): C 60.49, H 5.36, N 11.76, S
8.97; found: C 60.27, H 5.63, N 11.75, S 8.68.
10. X-Ray Crystal-Structure Determination of 14f, 16a, and 17a (see Table 6, and Figs. 1 and 2)3). All
measurements were conducted using graphite-monochromated MoKa radiation (l 0.71073 ä) on a Rigaku
AFC5R diffractometer fitted to a 12-kW rotating-anode generator (16a and 17a) or on a Nonius KappaCCD
area-detector diffractometer [46] equipped with an Oxford Cryosystems Cryostream 700 cooler (14f). The data
collection and refinement parameters are given in Table 6, and views of the molecules are shown in Figs. 1 and 2.
Data reduction for 14f was performed with HKL Denzo and Scalepack [47]. The intensities were corrected for
Lorentz and polarization effects, but not for absorption. Each structure was solved by direct methods using
SIR92 (14f and 17a) [48] or SHELXS97 (16a) [49], which revealed the positions of all non-H-atoms. The non-H-
atoms were refined anisotropically. The amine H-atoms of 14f were placed in the positions indicated by a
difference-electron-density map, and their positions were allowed to refine together with individual isotropic
displacement parameters. All remaining H-atoms of 14f and all H-atoms of 16a and 17a were placed in
geometrically calculated positions, and each was assigned a fixed isotropic displacement parameter with a value
equal to 1.2Ueq of its parent C-atom. Refinement of each structure was carried out on F using full-matrix least-
squares procedures, which minimized the function Sw(j Fo jÀj Fc j )2 where w ˆ [s2(Fo) ‡ (pFo)2]À1. A correction
for secondary extinction was applied in the cases of 16a and 17a. For 14f, three reflections, whose intensities
were considered to be extreme outliers, were omitted from the final refinement. Neutral-atom-scattering factors
for non-H-atoms were taken from [50a], and the scattering factors for H-atoms were taken from [51].
Anomalous dispersion effects were included in Fc [52]; the values for f' and f'' were those of [50b]. The values of
the mass attenuation coefficients are those of [50c]. All calculations were performed using the teXsan
crystallographic software package [53].
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Received March 18, 2004