Cathodic reduction of N-(2-iodophenyl)-N-alkylcinnamides: A novel sequential electrochemical radical cyclisation and hydroxylation

Article abstract of DOI:10.1039/b100418m

In recent years, intramolecular aryl radical cyclisation has emerged as a useful route for the synthesis of benzannulated heterocycles and carbocycles. The aryl radicals are generated in situ from aryl halides (iodides or bromides) with tributylstannyl hydride-AIBN, SmI₂, Co(I) or under photochemical conditions. The present work envisages the generation of aryl radicals by cathodic reduction of the carbon-iodine bond of N-(2-iodophenyl)-N-alkylcinnamides and their intramolecular cyclisation. The cathodic reduction of N-(2-iodophenyl)-N-alkyl-cinnamides under deaerated conditions in DMF gave 1-alkyl-3-benzylindolin-2-ones regioselectively and in the presence of oxygen yielded surprisingly 1-alkyl-3-hydroxy-3-benzylindolin-2-ones. Both these products were formed by a 5-exo-trig process in good yields. A mechanism for the formation of the products has been proposed through the use of cyclic voltammetry, coulometry and controlled-potential electrolysis as well as deuterium labelling.

Full text of DOI:10.1039/b100418m

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Cathodic reduction of N-(2-iodophenyl)-N-alkylcinnamides: a novel
sequential electrochemical radical cyclisation and hydroxylation
Raja Munusamy,a Kaveripatnam Samban Dhathathreyan,a
Kalpattu Kuppusamy Balasubramanianb and Chitoor Sivaramakrishnan Venkatachalamb
2
a Centre for Energy Research, SPIC Science Foundation, 111, Mount Road, Guindy,
Chennai-600032, India
b Department of Chemistry, Indian Institute of Technology, Madras, Chennai-600036, India
Received (in Cambridge, UK) 9th January 2001, Accepted 27th April 2001
First published as an Advance Article on the web 11th June 2001
In recent years, intramolecular aryl radical cyclisation has emerged as a useful route for the synthesis of
benzannulated heterocycles and carbocycles. The aryl radicals are generated in situ from aryl halides (iodides or
bromides) with tributylstannyl hydride–AIBN, SmI2, Co() or under photochemical conditions. The present work
envisages the generation of aryl radicals by cathodic reduction of the carbon–iodine bond of N-(2-iodophenyl)-
N-alkylcinnamides and their intramolecular cyclisation. The cathodic reduction of N-(2-iodophenyl)-N-alkyl-
cinnamides under deaerated conditions in DMF gave 1-alkyl-3-benzylindolin-2-ones regioselectively and in the
presence of oxygen yielded surprisingly 1-alkyl-3-hydroxy-3-benzylindolin-2-ones. Both these products were formed
by a 5-exo-trig process in good yields. A mechanism for the formation of the products has been proposed through
the use of cyclic voltammetry, coulometry and controlled-potential electrolysis as well as deuterium labelling.
Table 1 Various amides of N-(2-iodophenyl)-N-alkylanilines and
α,β-unsaturated acids
Introduction
There continues to be an immense interest in intra- and inter-
molecular electrochemical cyclisation reactions of dicarbonyl,
olefinic carbonyl and α,β-unsaturated carbonyl compounds
with respect to the mechanistic details of the cyclisation pro-
cesses and subsequent developments of practical electro-
syntheses based on the electrolyses of these compounds.1 The
electrochemically induced intramolecular tethering of a variety
of activated carbonyls,2 and olefinic3 and allenic groups4 on to
an aldehyde or a ketone and electrochemically induced Diels–
Alder reactions1,5 and electrocyclic ring6 closure reactions
are well known. The utility of tributylstannyl radical-mediated
cyclisation in the syntheses of benzannulated carbocycles7 and
heterocycles8 is well documented. Intramolecular cyclisation
of N-(2-iodophenyl)-N-α,β-unsaturated carboxamides under
Pd()-catalyzed,9 Sm()10 or Co()11 and photochemically
induced12 conditions has been investigated. These reactions
led to a mixture of products while the tributylstannyl radical-
mediated cyclisation of N-(2-iodophenyl)-N-alkylcinnamides
Compound
R1
R2
R3
X
1a
1b
1c
1d
1e
1f
1g
1h
1i
CH3
CH3
CH3
CH3
CH3
CH3
Cl
Cl
Br
H
H
PhCH2
PhCH2
H
CH3
PhCH᎐CH
PhCH᎐CH
PhCH᎐CH
PhCH᎐CH
PhCH᎐CH
PhCH᎐CH
PhCH᎐CH
I
—
I
I
I
I
I
I
I
᎐
᎐
᎐
᎐
᎐
᎐
᎐
᎐
CH3
CH3CH2
PhCH2
CH3
PhCH2
PhCH2
CH3
PhCH᎐CH
PhCH᎐CH
PhCH᎐CH
1j
1k
I
I
᎐
᎐
PhCH2
afforded
1-alkyl-3-benzylindolin-2-ones
regioselectively.13
alkylcinnamides in aerated media undergo reductive cyclisation
to form 1-alkyl-3-benzylindolin-2-ones, which get oxidized
to 1-alkyl-3-hydroxy-3-benzylindolin-2-ones by the superoxide
generated in situ from the cathodic reduction of oxygen.
Though α-hydroxylation of ketones17 and indolin-2-ones18 by
oxygen in alkaline media and the anodic hydroxylations of
carbonyl compounds19 in methanol containing potassium
iodide are known, the hydroxylation of carbonyl compounds
under cathodic conditions in the presence of oxygen has not
yet been reported.
Strangely, reports on the electrochemically induced aryl radical
cyclisation are scarce and mainly confined to 2-halo-
benzanilides,14 iodobenzylisoquinolinium salts15 and enamin-
ones.16 The potential of this technique for radical cyclisation
methodology has not been fully explored. It will be interesting
to generate the aryl radical or aryl anion of N-(2-iodophenyl)-
N-alkylcinnamides by cathodic reduction of the carbon–iodine
bond and study the chemical behavior of these radicals/anions
(Scheme 1), particularly in the light of published work on
the intramolecular cyclisation of these amides under tributyl-
stannyl radical-mediated (tributylstannyl hydride–AIBN)
conditions.13 N-(2-Iodophenyl)-N-alkylcinnamides undergo
cathodic cyclisation and afforded 1-alkyl-3-benzylindolin-2-
ones regioselectively. Surprisingly, electrolyses of N-(2-iodo-
phenyl)-N-alkylcinnamides in DMF solutions in the presence
of oxygen yielded 1-alkyl-3-hydroxy-3-benzylindolin-2-ones.
This has prompted us to investigate the mechanism of this
cathodic cyclisation and hydroxylation using deuterium-
labelled substrates, which revealed that N-(2-iodophenyl)-N-
Results and discussion
Cyclic voltammetry of N-(2-iodophenyl)-N-alkylcinnamides
Various N-(2-iodophenyl)-N-alkylcinnamides were prepared
according to the literature procedure13 and characterised (Table
1). The cyclic voltammetric (CV) studies of 1a–1k (5.0 × 10Ϫ3
M, Table 2) at a hanging mercury drop electrode (hmde) and
at various sweep rates were performed in DMF containing
1154
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b100418m

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Scheme 1
Table 2 CV data of amides 1a–1k (5.0 × 10Ϫ3 M) in DMF at 100 mV
Ϫ1 sweep rate
s
First cathodic peak
Second cathodic peak
Potential
Current
ip,cI/µA
Potential
Current
ip,cII/µA
Compound
ϪEp,cI/Va
ϪEp,cII/Va
1a
1b
1c
1d
1e
1f
1g
1h
1i
1.49
1.69
1.47
1.59
1.59
1.48
1.32
1.20
1.14
1.57
1.43
30.19
24.10
25.90
47.10
43.50
40.90
40.61
31.30
36.90
52.46
37.58
—
—
2.12
1.74
1.75
1.77
1.68
1.72
1.64
1.66
1.74
1.62
15.33
28.70
24.10
23.90
20.30
19.62
25.50
34.05
24.42
19.70
1j
1k
Fig. 1 Cyclic voltammogram of 1f (5.0 × 10Ϫ3 M) in DMF at 100 mV
Ϫ1 sweep rate.
a Measured versus a silver quasi-reversible electrode.
s
Table 3 Anodic peak currents ip,aIII of 1f under cyclic voltammetric
conditions during potential-hold experiments
tetrabutylammonium perchlorate (TBAP) as the supporting
electrolyte. These studies were carried out to ascertain the
reduction potentials of the C–I bond and C᎐C double bond in
Duration of
holding/s
Anodic peak
current ip,aIII/µA
᎐
the substrates. The CV data obtained are presented in Table 2.
It may be pointed out that N-(2-iodo-4-methylphenyl)-N-
benzylacetamide, 1a, gave an irreversible peak at Ϫ1.49 V and
N-(4-methylphenyl)-N-benzylcinnamide, 1b, gave two irrevers-
ible cathodic peaks at Ϫ1.69 and Ϫ2.12 V, respectively. All the
other amides, 1c–1k showed two irreversible cathodic peaks.
The first cathodic peak is due to the reduction of the C–I bond,
0
10
20
30
40
50
60
75
90
4.01
7.37
8.65
8.83
8.85
8.91
8.95
9.43
9.41
whereas the second cathodic peak is due to C᎐C bond reduc-
᎐
tion. Linear plots of the square root of the sweep rates versus
the cathodic peak currents of 1a–1k, passing through the origin
at all concentrations, suggest the diffusion-limited nature of the
electrode processes. A typical cyclic voltammogram of 1f is
shown in Fig. 1.
While scanning in the reverse direction, a quasi-reversible
anodic peak III (Fig. 1) appeared in the potential region of 0
to Ϫ0.4 V at all sweep rates. The anodic peak III appeared
even when the potential scan was stopped and reversed at the
potential of the first cathodic peak (C–I bond reduction). The
appearance of anodic peak III in the reverse scan of 1f in DMF
is due to the oxidation of the species formed on the electrode
surface at the end of the first cathodic peak. This observation
has been confirmed by potential-hold experiments as described
below. When the potential of the working electrode (hmde) in
cyclic voltammetry at a given sweep rate was held at Ϫ1.55 V
(called the switching potential after the first cathodic peak) for
small intervals of time (0 to 90 s) and then the sweep reversed,
the anodic peak currents ip,aIII were found to increase gradually
with holding time (Table 3) and then reached a limiting value
when the holding time was further increased to 90 s. These
findings clearly indicate that the anodic peak III is due to the
oxidation of the species generated at the cathodic potential
corresponding to the first cathodic peak during the forward
scan.
Microcoulometry
Microcoulometric studies of 1a–1d (Table 4) were carried out
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166
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Percentage yields of the electrolysis products 1-alkyl-
3-benzylindolin-2-ones 7d–7k
Table 4 Microcoulometric data of amides 1a–1d in DMF
Table 5
Potential of
Substrate
electrolysis ϪE/Va
nb
Cyclised
Carbon–iodine
compound
7c–7k
reduction
product 6c–6k
Compound
1a
1b
1c
1d
1.8
1.8
1.8
1.8
1.90
2.00
3.90
2.00
1c
1d
1e
1f
1g
1h
1i
—
70
75
85
75
80
85
75
80
75
10
5
—
—
—
—
10
—
a Measured vs. a silver quasi-reversible electrode. b No. of electrons
transferred.
under polarographic conditions in DMF in order to find out
the number of electrons transferred in the reduction process.
The amides 1a and 1b, respectively, consumed two electrons
1j
1k
each corresponding to the reduction of the C–I and C᎐C bonds.
᎐
Although the amides 1c and 1d, as mentioned earlier, showed
two cathodic peaks (irreversible) under cyclic voltammetric
conditions, they displayed only a single wave in polarography.
The microcoulometric studies of amide 1d at the limiting region
of the polarogram (corresponding to the second cathodic peak
in cyclic voltammetry) indicate a transfer of two electrons,
which is in contrast to 1c for which a transfer of four electrons
was observed in the reduction (Table 4). In the normal course
of independent reduction of the C–I bond and reduction of
C᎐O of the electrolysis product, 7d, is shifted further downfield
᎐
viz. to 176.94 ppm. The spectral data clearly indicate that the
product 7d is 1,5-dimethyl-3-benzylindolin-2-one and not 1,6-
dimethyl-4-phenyl-3,4-dihydroquinolin-2(1H)-one. The struc-
tures of the electrolysis products (7d and 7f) in the cases of 1d
and 1f have been further confirmed by comparison with respec-
tive authentic samples prepared independently by chemical
methods.13 The IR spectrum of the other electrolysis product
with Rf = 0.60 showed a band at 1650 cmϪ1 due to C᎐O and
᎐
the C᎐C bond, the number of electrons transferred would have
another band at 1603 cmϪ1 due to the C᎐C bond. Furthermore,
᎐
᎐
been four, but microcoulometric experiments in the case of 1d
(at the end of the second wave, Ϫ1.80 V) showed a transfer of
only two electrons. The number of electrons transferred for the
reduction of the above amides in DMF (1d–1k) was further
confirmed independently from current vs. time (i–t) curves
under potentiostatic conditions and was found to be two.
the signals at δ (ppm) 6.10 (1H, d, J1,2 = 16 Hz, -NCOCH᎐
᎐
CHPh) and 7.55–7.78 (1H, d, J1,2 = 16 Hz, -NCOCH᎐CHPh) in
᎐
1
the H NMR spectrum and 13 signals in the 13C NMR spec-
trum revealed it to be the product of simple reduction of the
C–I bond, namely 6d, an observation which has been further
confirmed by comparison with an authentic sample of 6d.
The cathodic cyclisation of the amides 1d–1k was found to be
highly regioselective. It may be pointed out that the compound
1c on macroelectrolysis (at Ϫ1.5 V vs. a silver quasi-reversible
electrode) afforded only the product of hydrogenolysis of
the C–I bond, viz. N-(4-methylphenyl)cinnamide. A similar
behavior was observed in tributylstannyl radical-mediated
cyclisation of 1c, which led only to simple reduction of the C–I
bond instead of any cyclisation.13 Since amides exhibit dynamic
E and Z isomerism, a mechanistic rationale based on restricted
rotation about the carbon–nitrogen bond was proposed to
account for the failure of the cyclisation of 1c.13,14a In the
cathodic reactions reported here, single-electron reduction
results in the formation of an aryl radical that tethers to the
Controlled-potential electrolysis
The controlled-potential electrolyses of 1c–1k (10.0 × 10Ϫ3 M)
were performed on a mercury pool cathode at Ϫ1.50 V in DMF
under deaerated conditions (electrolytic hydrogen–argon). For
example, the catholyte of 1d, after work-up, afforded a viscous
liquid in 90% yield (crude). According to Scheme 1, the electro-
reduction of the C–I bond leads to either the aryl radical or
aryl anion depending on the number of electrons transferred,
namely, one or two. The aryl radical/anion thus generated can
undergo intramolecular cyclisation by either a 5-exo-trig or a
6-endo-trig process, as outlined in Scheme 1, to afford 1,5-
dialkyl-3-benzylindolin-2-one or 1,6-dialkyl-3-phenyl-2-quinol-
one, respectively.
α-position of the C᎐C bond by a 5-exo-trig process (Scheme 1).
᎐
The yield of 1-alkyl-3-benzylindolin-2-one is marginally influ-
enced by the substituents on the aromatic ring and the alkyl
group on the nitrogen atom. For example, when the N-methyl
group (1d) was replaced by bulkier benzyl group (1f), the
yield of the cyclised compound rose to 85% (Table 5) and
the reaction was found to be general for all the amides studied.
Thin layer chromatography of the crude product of elec-
trolysis of 1d (6d and 7d, Table 5) showed two spots (Rf = 0.70
and 0.60), which were separated by flash column chrom-
atography over silica. The major product, 7d with Rf =
0.70, showed a molecular ion-peak at 251.131085 in the high
resolution mass spectrum (HRMS). The molecular ion-peak
observed at 251.131085 in HRMS was very close to that calcu-
lated for the molecular formula, C17H17NO. The 1H NMR spec-
trum of 7d showed signals at δ (ppm) 2.21 (3H, s, -CH3), 2.77–
2.92 (1H, dd, J1,1Ј = 13 Hz, 8 Hz, -CHCH2Ph), 3.12 (s, 3H,
-NCH3), 2.86 (1H, dd, J1,1Ј = 13 Hz, J1,2 = 4 Hz, -CHCH2Ph),
3.69 (1H, dd, J1,2 = 4 Hz, J1,2 = 8 Hz, -CHCH2Ph), 6.65 (2H,
m, Ph), 6.93–7.30 (6H, m, Ph). The 13C NMR spectrum of 7d
exhibited signals at δ (ppm) 21.04 (q), 26.08 (q), 36.81 (t), 47.07
(d), 107.52 (d), 125.38 (d), 126.54 (s), 127.88 (s), 128.42 (d),
128.87 (d), 129.37 (d), 131.42 (d), 138.03 (s), 141.80 (s), 176.94
Mechanism
The observation of a two electron-transfer in the reduction of
amides 1a, 1b and 1d and cathodic cyclisation of 1d–1k to give
the corresponding cyclised and C–I bond reduced products
suggests an electrochemical and chemical reaction sequence.
The first step is the generation of aryl radical 2 (Scheme 2) by
single-electron reduction of the C–I bond. The subsequent step
may involve either the intramolecular aryl radical cyclisation by
a 5-exo-trig process to furnish 7 or transfer of another electron
by a cathodic process to an anion, 3, which is further proton-
ated to give the C–I bond reduced product 6 (Scheme 2). Since
these reactions are parallel reactions, the relative rates of intra-
molecular cyclisation of the aryl radical (2 to 4, Scheme 2) and
the reduction of the aryl radical (2 to 3) will determine the ratio
of the products. The proposed mechanism outlined in Scheme 2
for the formation of 1-alkyl-3-benzylindolin-2-ones is an ECEC
(C᎐O). The IR spectrum of 7d showed a band at 1699 cmϪ1 due
᎐
to the carbonyl group. A remarkable feature in the IR spectrum
is that the band at 1619 cmϪ1 due to the C᎐C bond [which was
᎐
present in the substrate (depolariser)] was absent and the band
at 1654 cmϪ1due to the C᎐O group was shifted to 1699 cmϪ1. In
᎐
the 13C NMR spectrum, the signal due to the carbon of C᎐O of
᎐
1d appears at 166.43 ppm, whereas that of the carbon of the
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Scheme 2
Table 6 Percentage yields of the electrolysis products 1-alkyl-3-
hydroxy-3-benzylindolin-2-ones 8d–8k
molecular ion peak at 343.154184 in its high resolution mass
spectrum (HRMS), close to that calculated for the molecular
formula, C23H21NO2. The IR spectrum of 8f showed a sharp
band at 1705 cmϪ1 due to the C᎐O group and, surprisingly,
Substrate
Yield of 8 (%)
᎐
a band at 3328 cmϪ1 and also confirmed the absence of a C᎐C
᎐
1d
1f
1g
1h
1i
1j
1k
75a
85a
80
85
85
bond.
The 1H NMR spectrum of 8f showed signals at δ (ppm)
2.25 (3H, s, -CH3), 3.25–3.44 (3H, AB q and s, J1,1Ј = 13 Hz,
-C(OH)CH2Ph), 4.41 (1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 4.95
(1H, d, J1,1Ј = 13 Hz, -NCH2Ph), 6.30 (1H, d, J1,2 = 7 Hz,
Ph), 6.66 (2H, m, Ph), 6.92 (2H, m, Ph), 7.1 (8H, m, Ph). The
13C NMR spectrum of 8f exhibited signals at δ (ppm) 21.06 (q),
43.69 (t), 44.82 (t), 76.36 (s), 109.30, 125.07, 126.63, 126.89,
127.24, 128.04, 128.59, 129.15, 129.96, 130.42, 132.53, 133.92,
75
85
a The dimers, 11d and 11f, respectively, were also isolated as minor
products in the case of the cathodic reduction of 1d and 1f at higher
concentrations.
135.02, 140.28, 177.61 (C᎐O). The broad signal at δ 3.25 ppm
᎐
disappeared on shaking with D2O indicating it to be due to an
OH proton. This observation and the band at 3328 cmϪ1 in the
IR spectrum suggest the presence of a hydroxy group in 8f,
which is further confirmed by the formation of 3-acetoxy-1,3-
dibenzyl-5-methylindolin-2-one, 9f, in 90% yield upon treat-
ment with acetic anhydride (Scheme 3), while under acidic
conditions, 8f underwent dehydration to give a mixture of E
and Z isomers of 1-benzyl-3-benzylidene-5-methylindolin-2-
one, 10f, in 75% yield.
In the case of 8k (Table 6), the structure of the product was
further confirmed by comparison with an authentic sample,
which was synthesized independently by chemical methods as
outlined in Scheme 4.20
(electrochemical–chemical–electrochemical–chemical) type pro-
cess, whereas the formation of the C–I bond reduced product is
of the EEC (electrochemical–electrochemical–chemical) type as
outlined in Scheme 2.
Cathodic cyclisation and hydroxylation of N-(2-iodophenyl)-N-
alkylcinnamides
Cathodic cyclisation of N-(2-iodophenyl)-N-alkylcinnamides
in the presence of oxygen. The controlled-potential electrolyses
of the solutions of 1d–1k (10.0 × 10Ϫ3 M) in DMF at Ϫ1.5 V vs.
a silver quasi-reversible electrode were carried out using a
mercury pool cathode in the presence of oxygen. For example,
the catholyte of 1f, after work-up, afforded a solid product
(mp 213–214 ЊC), 8f, in 85% yield which has not been reported
in the literature (Scheme 3, Table 6). The product 8f showed a
Scheme 4
The AB quartet centered at δ 3.25 ppm (J1,1 = 13 Hz) in
1
the H NMR spectrum is due to the diastereotopic benzylic
protons at 3-C. The signal at δ 77.64 ppm (s) in the 13C NMR
spectrum of 8f can be assigned to the carbon atom at the
3-position of the indole ring. All the amides (1d–1k, Table 6)
on electrolysis afforded the corresponding 1-alkyl-3-hydroxy-
3-benzylindolin-2-ones (8d–8k) in good yields. It is interesting
to note that electrolyses of 1d and 1f in DMF solutions at
higher concentrations (20 mM) afforded dimers, 11d and 11f
(Scheme 5), respectively, in minor amounts together with the
hydroxylated products, 8d and 8f. All the electrolysis products
were isolated and thoroughly characterized by spectral
means.
Scheme 3
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Mechanistic studies. While formation of the hydroxylated
product in the present work under cathodic conditions is quite
unprecedented, the formation of the tertiary alcohol 8 (Scheme
5) was even more intriguing as the sequential single-electron
reduction of the C–I bond, 5-exo-trig cyclisation and hydroxyl-
ation of the resulting radical, 3, should have led to secondary
alcohol 14 and not to 8 (Scheme 6).
As the cathodic cyclisation N-(2-iodophenyl)-N-alkyl-
cinnamides 1d–1k (presented in Scheme 6) is very similar to
tributylstannyl radical-mediated cyclisations,13 we examined
the radical cyclisation of 1f (Table 6) with tributylstannyl-
deuteride–AIBN (Scheme 9) and that of 1l with tributylstannyl
hydride–AIBN (Scheme 10) in order to find out whether any
A mechanism involving the rearrangement of the secondary
radical 4 to the more stable tertiary radical 12 was initially
conceived to account for the formation of 8 and the dimer 11
(Scheme 6). Since 1,2-hydrogen shifts are rarely encountered in
free radical rearrangements, it became imperative to establish
the 1,2-hydrogen shift envisaged in Scheme 6 by labelling
experiments.
(a) Isotope labelling experiments. The α-deuteriocinnamide,
1l was synthesized as outlined in Scheme 7. Electrolysis of
α-deuteriocinnamide 1l was performed in DMF in the presence
of oxygen. According to the mechanism speculated in Scheme
6, the cathodic reductive cyclisation of 1l should have furnished
3-(α-deuterobenzyl)-3-hydroxyindolin-2-one, 8p through a 1,2-
deuterium shift (Scheme 8). However, characterisation of the
electrolysis product by NMR spectroscopy and mass spec-
trometry showed the absence of deuterium in the product and
confirmed it to be 8f (Scheme 8).
Scheme 7
Scheme 5
Scheme 8 Cathodic cyclisation of 1l in DMF in the presence of oxygen.
Scheme 6
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ring, it can be expected to be acidic enough to undergo
exchange by rapid enolisation–ketonisation under silica gel
chromatographic conditions and thus 7l might have undergone
rapid exchange. This was apparent from the fact that when
compound 7f was dissolved in CDCl3 and the solution of 7f was
allowed to equilibrate with D2O and the NMR spectrum
subsequently recorded, the 1H NMR spectrum clearly revealed
that the 3-C proton, α to the carbonyl group had undergone
exchange. The spectrum exhibited signals at δ (ppm) 2.25 (3H,
s, -CH3), 3.15 (1H, d, J1,1 = 14 Hz, -CDCH2Ph ), 3.40 (d, 1H,
J1,1 = 14 Hz, -CDCH2Ph), 4.60 (d, 1H, J1,1 = 16 Hz, -NCH2Ph),
4.98 (1H, d, J1,1 = 16 Hz, -NCH2Ph), 6.40 (1H, d, J1,2 = 8 Hz,
Ph), 6.80–6.90 (4H, m, Ph), 7.06–7.34 (8H, m, Ph). The signal
at δ (ppm) 3.5 (dd), due to the hydrogen at 3-C, disappeared
and so did the coupling of this hydrogen with neighboring
protons at δ (ppm) 3.15 and 3.40. The 13C NMR spectrum
after exchange with D2O exhibited signals at δ (ppm) 21.03
(q), 36.21 (t), 43.63 (t), 47.07 (deuterium-attached carbon),
109.06 (d), 125.24 (d), 126.64 (d), 126.74 (d), 127.29 (d),
128.19 (d), 128.58 (d), 129.59 (d), 132.07 (d), 135.07, 136.95,
Scheme 9 Radical cyclisation of 1f (Bu3SnD–AIBN).
140.56, 177.89 (C᎐O). The D O was removed from the NMR
᎐
2
tube with the help of a syringe and water was added, the
NMR solution shaken and the NMR spectrum was recorded
again and was identical to that of 7f. These studies confirm
the labile nature of the deuterium at the 3-carbon of indolin-
2-one 7l.
1,2-Hydrogen migrations in free radical reactions are much
less prevalent and more important only for aryl21 and halogen22
migrating groups. The direction of the rearrangement is
normally towards the formation of the more stable radical.
Hence, the tributylstannyl radical-mediated cyclisation of 1n
(Scheme 11) was carried out in order to find out whether such
Scheme 10 Cathodic and radical cyclisation of 1l (Bu3SnH–AIBN).
1,2-hydrogen shift occurs in these radical cyclisation reac-
tions. However, radical cyclisation of 1f with tributylstannyl
deuteride–AIBN furnished only 7m (Scheme 9) and none of 7l.
The same outcome has been further confirmed by performing
electrochemically induced cyclisations of compound 1l (Scheme
10), which, after aqueous work-up, led only to the formation of
product 7f and not 7m, thus ruling out the mechanism origin-
ally envisaged (Scheme 6). Likewise, tributylstannyl radical-
mediated cyclisation of 1l afforded only 7f (Scheme 10) and
none of 7l or the product of 1,2-deuterium shift, viz. 7m. The
formation of the product 7f was rather surprising. It was
suspected that the deuterium-labelled product 7l, formed by
the cyclisation, might have undergone reverse exchange with
water during work-up. To rule this out, the product of radical-
mediated cyclisation of 1l was isolated from a non-aqueous
work-up by evaporating the toluene under vacuum and sub-
jecting the crude product to column chromatographic purifi-
cation. Characterization of the product by NMR spectroscopy
revealed that it was nothing but 7f. This could be possible only
if the deuterium at 3-C is highly labile. Since the deuterium is
Scheme 11 Radical cyclisation of 1n (Bu3SnH–AIBN).
a 1,2-free radical rearrangement occurs when hydrogen is
replaced by a phenyl group. This reaction afforded 7n as the
only product and not 7o (Scheme 11), suggesting that there is
no rearrangement of the radical formed during the cyclisation
process.
(b) Electrolysis products and time of electrolysis. To follow
the course of the above electrochemical cyclisation and
hydroxylation reaction, controlled-potential electrolysis of 1f
(10.0 × 10Ϫ3 M) was carried out in DMF in the presence of
oxygen at various time intervals and the yields of the products
were determined (Table 7). It was found that at the beginning
of the electrolysis 1,3-dibenzyl-5-methylindolin-2-one 7f, is
formed. The percentage yields of 1,3-dibenzyl-5-methylindolin-
2-one, 7f and 1,3-dibenzyl-3-hydroxy-5-methylindolin-2-one 8f
at different intervals of time are given in Table 7.
bonded to a carbon that is α to the C᎐O group and aromatic
᎐
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166
1159

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Scheme 12
Table 7 Percentage yields of 7f and 8f during the electrolysis of 1f
in DMF
Yield (%)
Electrolysis
time/min
7f
8f
45
90
150
240
300
30
25
15
10
0
40
55
70
80
85
It can be seen from Table 7 that the product 7f, which is
formed immediately, undergoes hydroxylation to form 8f. This
observation suggests that the transformation of 1 to 8 occurs
through the hydroxylation of an intermediate, 7 (Scheme 12),
by oxygen to form 8. The oxidation of 7 to 8 is found to be an
electrochemical reaction and not a chemical reaction as shown
by the following observations. In a controlled experiment,
purging a solution of 1,3-dibenzyl-5-methylindolin-2-one 7f in
DMF (containing TBAP supporting electrolyte) with oxygen
did not yield 1,3-dibenzyl-3-hydroxy-5-methylindolin-2-one, 8f.
On the other hand, electrolysis of 7f under aerated conditions
at Ϫ0.8 V vs. a silver quasi-reversible electrode in DMF solu-
tions (in an H-shaped divided cell equipped with a mercury
pool cathode and platinum foil anode) afforded 8f in 85% yield.
(c) Cyclic voltammetry of 7f in the presence of oxygen. With a
view to understanding the mechanism of the electrochemical
hydroxylation reaction of 7 to 8 (Scheme 12), a cyclic voltam-
metric study of 7f (5.0 × 10Ϫ3 M) in DMF was undertaken. The
cyclic voltammogram of oxygen (saturated) in DMF solution
at a hanging mercury drop electrode and 300 mV sϪ1 sweep
Fig. 2 Cyclic voltammograms of oxygen saturated in DMF (a) in the
absence of 1,3-dibenzyl-5-methylindolin-2-one 7f and (b) in the pres-
ence of 5.0 × 10Ϫ3 M of 1,3-dibenzyl-5-methylindolin-2-one 7f at a
sweep rate of 300 mV sϪ1
.
Ϫ
rate showed a quasi-reversible cathodic peak (due to O2
᝽
formation) at Ϫ0.75 V vs. a quasi-reversible silver electrode23
(Fig. 2).
It may be mentioned that 1,3-dibenzyl-5-methylindolin-2-
one, 7f was not electro-active in the potential region from 0 to
Ϫ1.5 V. During the reverse scan, the decrease in the anodic
current in the cyclic voltammogram of oxygen in the presence
of 7f (Fig. 2) suggests the formation of an intermediate at the
electrode/solution interface due to the interaction of the
superoxide radical generated in situ (by reduction of oxygen)
with 1,3-dibenzyl-5-methylindolin-2-one 7f. The involvement
of 1,3-dibenzyl-5-methylindolin-2-one 7f in the depletion of
superoxide from the mercury surface (electrode) is further
1160
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166

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Table 10 Percentage yields of 8f during the hydroxylation of 7f
Table 8 CV data of oxygen for the first cathodic peak in the presence
of various concentrations of 1,3-dibenzyl-5-methylindolin-2-one 7f in
DMF at 100 mV sϪ1 sweep rate
NaH : 7f
mole ratio
Yield (%)
Concentration/
mM
Cathodic peak
current ip,cI/µA
Anodic peak
current ip,aI/µA
2.00
1.00
0.50
0.15
85
88
87
85
0
5
7.5
10
15
94.3
93.9
93.4
92.0
93.2
27.2
8.9
4.4
3.4
1.5
ations afford a mixture of products. The electrochemical
method of cyclisation reported in the present work is not only
novel, but also complementary to the existing radical cyclis-
ationmethodologies,viz.tributylstannylradical-mediatedcyclis-
ation and SmI2-mediated radical cyclisation for the synthesis of
1-alkyl-3-benzylindolin-2-ones. In the presence of oxygen, elec-
trolyses of N-(2-iodophenyl)-N-alkylcinnamides afford 1-alkyl-
3-hydroxy-3-benzylindolin-2-ones. The experimental evidence
suggests a reaction pathway as outlined in Scheme 12, in which
the formation of 1-alkyl-3-hydroxy-3-benzylindolin-2-ones
involves the interaction of 1-alkyl-3-benzylindolin-2-one with
the superoxide generated in situ from molecular oxygen by
cathodic reduction. The transformation involving the sequen-
tial radical cyclisation and hydroxylation under cathodic
conditions is novel, of mechanistic interest and also without
precedence.
Table 9 Percentage yields of 8f during the electrolysis of 7f
Quantity of
electricity passed/
F moleϪ1
Yield (%)
4.5
1.0
0.5
0.1
85
87
88
85
confirmed by the effect of varying the concentration of 1,3-
dibenzyl-5-methylindolin-2-one 7f on the anodic peak currents
due to superoxide oxidation in cyclic voltammetry. Table 8 sug-
gests that with an increase in the concentration of 7f, the anodic
peak currents due to the oxidation of superoxide to oxygen
decreased substantially. The decrease in the anodic peak cur-
rents is attributed to the depletion of superoxide caused by the
interaction of superoxide with 1,3-dibenzyl-5-methylindolin-2-
one intermediate, 7f, and hence is not available for oxidation
(Table 8). The mechanism depicted in Scheme 12 would account
for the observed sequential electrochemical reductive cyclis-
ation and hydroxylation.
The hydroxylation reaction of 1,3-dibenzyl-5-methylindolin-
2-one, 7f with superoxide may proceed by abstraction of either
hydrogen or a proton to form a radical, 12, or an anion, 15
(Scheme 12). Enolates similar to 15 generated from 3-alkyl-
indolin-2-ones are known to react with molecular oxygen to
furnish 3-hydroxy-3-alkylindolin-2-ones.17 In the present case
also the anion of 1,3-disubstituted indolin-2-ones (generated in
DMF by reaction of 7f with NaH) underwent oxidation to give
8f presumably through the radical, 12.18 With a view to finding
out whether oxidation of 7f is a chain reaction initiated by the
electrochemically generated superoxide or a stoichiometric
process involving superoxide, the electrolysis of a solution of 7f
was carried out by passing various amounts of current (nitro-
gen containing 3% oxygen was bubbled through the solution
continuously at a flow rate of 100 mL minϪ1). The percentage
yields of 8f obtained in the electrolysis are presented in Table 9.
The yield of 8f did not depend on the quantity of electricity
passed, which suggests that a catalytic amount of electricity is
sufficient for the completion of the reaction (Table 9).
Experimental
General
Solvents were dried by standard methods and freshly distilled
1
prior to use. H NMR (200 MHz) and 13C NMR (50 MHz)
spectra were recorded on a Bruker spectrometer at room tem-
perature using CDCl3 as solvent and tetramethylsilane as the
reference, unless otherwise mentioned. Mass spectral analyses
were carried out using a Shimadzu mass detector model
GCMS-QP 5000 at 70 eV. High resolution mass spectral data
were obtained on a Finnigan Mat8230 spectrometer. Melting
points are uncorrected. All the electrochemical studies were
carried out with microprocessor-controlled potentiostat/
galvanostat, EG&G, Princeton Applied Research Corporation,
USA.
Preparation of N-(2-iodo-4-substituted-phenyl)-N-alkyl-
cinnamides (1a–1k)
The substrate molecules (1a–1k, Table 1) were prepared by
acylation of the corresponding 2-iodoanilines (2-iodo-4-
methylaniline, 2-iodo-4-chloroaniline, 2-iodo-4-bromoaniline,
and 2-iodoaniline, respectively) with cinnamoyl chloride, fol-
lowed by alkylation of the resulting amides with NaH and the
corresponding alkyl halide (CH3I, PhCH2Br and EtBr) in DMF
according to the procedure previously reported.13 Likewise,
deuterium-labelled
N-(2-iodophenyl)-N-benzyl(α-deuterio)-
The hydroxylation of 7f by oxidation of its conjugate base
15f (Scheme 12) was also investigated. The amount of base was
varied and the yields of the hydroxylated product 8f were
estimated and the results are shown in Table 10. As can be seen
from the data given in Table 10, the hydroxylation of 7f occurs
smoothly using a catalytic amount of NaH in the presence of
oxygen. Further, the above observations clearly indicate that the
hydroxylation reaction of 7f is a chain reaction as shown in
Scheme 12.
cinnamide, 1k, was prepared using PhCH᎐CDCOCl, 2-iodo-4-
methylaniline and benzyl bromide.
᎐
Preparation of ꢀ-deuteriocinnamic acid
A mixture of 8.3 × 10Ϫ3 mol of methyl α-bromocinnamate,
1.0 × 10Ϫ2 mol of tributylstannyl deuteride and 1.0 × 10Ϫ4 mol
of AIBN in toluene was left under a nitrogen atmosphere for
8 h. The toluene was distilled off under vacuum and the
reaction mixture was dissolved in 25 mL of a water–methanol
mixture (1 : 1 v/v). The reaction mixture was treated with 1.0 g
of ammonium fluoride to convert the tributyltin compound
into the tin fluoride. The product was extracted with ethyl
acetate and the tin fluoride was removed as an insoluble solid.
Methyl (α-deuterio)cinnamate was hydrolyzed by boiling with
20 mL of an aqueous 1 M NaOH solution under refluxing
Conclusions
The cathodic cyclisation of N-(2-iodophenyl)-N-alkyl-
cinnamides in DMF under deaerated conditions affords regio-
selectively the product of a 5-exo-trig process in good yields,
whereas the photochemical and samarium()-induced cyclis-
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166
1161

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conditions. The reaction was acidified with 25 mL of 1 M sul-
furic acid and the product was precipitated. The product was
recrystallised from methanol. This method gave α-deuterio-
cinnamic acid with 85% deuterium incorporation. The deuter-
distilled off under vacuum and the residue was dissolved in 25
mL of a methanol–water mixture (1 : 1). The reaction mixture
was treated with 0. 5 g of ammonium fluoride to remove the tin
compounds and the compound extracted with ethyl acetate and
purified by column chromatography. The yield of the product 7i
was 85%.
1
ium content was determined by integration of the H NMR
signal at δ (ppm) 6.47 (J1,2 = 16.0 Hz) and 7.81 (J1,2 = 16.0 Hz)
relative to the α- (unlabelled) and β-protons, respectively, of the
acid. The literature method24 for the preparation of α-deuterio-
cinnamic acid by Dobner condensation of benzaldehyde with
CD2(COOD)2 in boiling pyridine afforded α-deuteriocinnamic
acid with an isotopic purity of 75%. Mp 130–131 ЊC. 1H NMR
(200 MHz; CDCl3) δ (ppm) 6.50 (0.15H, J1,2 = 16.0 Hz, iso-
Synthesis of 3-hydroxy-1,3-dibenzylindolin-2-one from indoline-
2,3-dione
A mixture of 1-benzylindoline-2,3-dione (4.5 × 10Ϫ3 mol),
benzyl bromide (5.0 × 10Ϫ3 mol), 0.50 mL of HBr (48% wt in
water) and 1.0 × 10Ϫ2 mol of tin powder (100 mesh) in THF was
refluxed for 10 h. The solvent was distilled off under vacuum
and the product was extracted with ethyl acetate and purified by
column chromatography.20 The yield of the product 8k was
75%. The spectral data of 8k obtained by this method were
compared with those for the electrolytically obtained 8k and
were found to be the same.
topic impurity, PhCH᎐CHCOOH), 7.25 (3H, m, Ph), 7.50 (2H,
᎐
m, Ph), 7.80 (1H, s, PhCH᎐CDCOOH), 9.80 (1H, br signal,
᎐
-COOH). 13C NMR (50 MHz; CDCl3) δ (ppm) 117.28, 128.34,
128.35, 128.53, 128.93, 130.71, 133.09, 133.99, 172.50 (C᎐O).
᎐
MS (70 eV) m/z (%) 150 (6), 149 (53), 148 (78), 132 (16), 104
(48), 103 (37), 92 (24), 78 (38), 77 (48).
Cathodic cyclisation of 1d–1k under deaerated conditions
N-(2-Iodo-4-methylphenyl)-N-benzylacetamide, 1a
The cyclic voltammetric studies of 1d–1k (5.0 × 10Ϫ3 M) in
DMF at various sweep rates were carried out using a hanging
mercury drop electrode (Metrohm, Switzerland) as working
electrode, a quasi-reversible silver electrode as a reference
electrode and a platinum electrode as the counter electrode.
Tetrabutylammonium perchlorate (TBAP) was used as the
supporting electrolyte throughout. The macroscale controlled-
potential electrolyses of 1d–1k (10.0 × 10Ϫ3 M) in DMF
solutions were performed in an H-type divided cell at –1.5 V
on a mercury pool cathode (10 cm2 area) under deaerated
conditions. For deaerating purposes, electrolytic hydrogen was
used.
Viscous liquid; νmax(CHCl3)/cmϪ1 1680 (C᎐O); δ (200 MHz;
CDCl3) 1.75 (3H, s, -COCH3), 2.30 (3H, s, -CH3), 3.70 (1H,
d, J1,1Ј = 16.0 Hz, -NCH2Ph), 5.60 (1H, d, J1,1Ј = 16.0 Hz,
-NCH2Ph), 6.5–7.50 (m, 7H, Ph) and 7.70 (m, 1H, Ph).
᎐
H
N-(4-Methylphenyl)-N-benzylcinnamide, 1b
Mp 82–83 ЊC (methanol); νmax(CHCl3)/cmϪ1 1660 (conj. C᎐O)
᎐
and 1619 (conj. C᎐C); λmax(CHCl3)/nm 284; δH (200 MHz;
᎐
CDCl3) 2.25 (3H, s, -CH3), 4.90 (2H, s, -NCH2Ph), 6.25 (1H, d,
J1,2 = 16 Hz, -NCOCH=CHPh), 6.75 (2H, d, J1,2 = 7 Hz, Ph),
7.50 (2H, d, J1,2 = 7 Hz, Ph), 7.55–7.60 (10H, m, Ph) and 7.75
(1H, d, J1,2 = 16 Hz, -NCOCH᎐CHPh); δ (50 MHz; CDCl3)
᎐
C
21.04, 53.27, 118.79, 125.77, 127.22, 127.80, 127.99, 128.29,
128.57, 129.42, 130.00, 135.16, 137.50, 137.63, 139.26, 142.16,
and 166.12.
Cathodic cyclisation of N-(2-iodophenyl)-N-alkylcinnamides in
the presence of oxygen
During the electrolyses of N-(2-iodophenyl)-N-alkyl-
cinnamides (10.0 × 10Ϫ3 M) in DMF solutions in the presence
of oxygen, the concentration of oxygen in the catholyte was
maintained steady and low by purging the electrolyte with
nitrogen containing 3% oxygen (flow rate 50 to 200 mL minϪ1).
The course of the reaction was monitored as a function of time
by coulometry and thin layer chromatography. The electrolysis
was stopped when the initial current (80 mA) reached a con-
stant minimum value of 15 mA after about 8 to 10 h. The DMF
was distilled off under vacuum and the products were isolated
by flash column chromatography. A mixture of ethyl acetate
and hexane was used as eluant.
N-(2-Iodo-4-methylphenyl)cinnamide, 1c
Mp 115–116 ЊC (methanol); νmax(CHCl3)/cmϪ1 1651 (conj.
C᎐O) and 1628 (conj. C᎐C); λmax(CHCl3)/nm 280; δH (200
᎐
᎐
MHz; CDCl3) 2.30 (3H, s, -CH3), 6.57 (1H, d, J1,2 = 16.0 Hz,
-NCOCH᎐CHPh), 7.20 (1H, d, J1,2 = 7 Hz, Ph), 7.30–7.60 (8H,
᎐
m, Ph), 7.70 (1H, d, J1,2 = 16.0 Hz, -NCOCH᎐CHPh) and 8.20
(1H, m, Ph).
᎐
N-(2-Iodo-4-methylphenyl)-N-methylcinnamide, 1d
Starting from 5.0 g of 2-iodo-4-methylaniline, 5.8 g of 1d were
obtained (75%); mp 117–118 ЊC (methanol); νmax(CHCl3)/cmϪ1
1654 vs (conj. C᎐O) and 1619 vs (conj. C᎐C); λmax(CHCl3)/nm
285; δH (200 MHz; CDCl3) 2.38 (3H, s -CH3), 3.35 (s, 3H,
᎐
᎐
Radical cyclisation of 1d, 1f, 1l and 1n
Reactant (1.0 × 10Ϫ2 mol) (1d, 1f, 1l and 1n), NaBH4 (2.0 × 10Ϫ2
mol), tributylstannyl chloride (3.5 × 10Ϫ4 mol) and AIBN
(1.0 × 10Ϫ4 mol) were refluxed in 100 mL of a toluene–
methanol mixture (20 : 1 v/v) under a nitrogen atmosphere for
8 h. The toluene–methanol was distilled off under vacuum and
the residue was dissolved in 25 mL of a methanol–water
mixture (1 : 1 v/v). The reaction mixture was treated with 0.5 g
ammonium fluoride to convert the tributyltin compound to the
tin fluoride. The products were extracted with ethyl acetate and
purified by column chromatography. The yields of the products
(7d, 7f, 7l and 7n) were 80, 85, 85 and 85%, respectively. The
spectral data of 7d and 7f obtained by electrochemical methods
were compared with those of the chemically synthesized 7d
and 7f.
-NCH3), 6.10 (1H, d, J1,2 = 16 Hz, -NCOCH᎐CHPh), 7.06–7.33
(4H, m, Ph), 7.55–7.78 (7H, m, Ph), 7.70 (1H, d, J1,2 = 16 Hz,
᎐
-NCOCH᎐CHPh) and 7.95 (1H, d, J1,3 = 3 Hz, Ph); δC (50
᎐
MHz; CDCl3) 21.03 (q), 36.83 (q), 99.89, 118.65, 128.33,
129.04, 129.32, 129.94, 131.08, 135.64, 140.64, 140.96, 142.73,
143.50 and 166.43 (C᎐O).
᎐
N-(2-Iodo-4-methylphenyl)-N-ethylcinnamide, 1e
Starting from 5.0 g of 2-iodo-4-methylaniline, 6.1 g of 1e were
obtained (70%); mp 44-45 ЊC (hexane); νmax(CHCl3)/cmϪ1 1660
vs (conj. C᎐O) and 1625 vs (conj. C᎐C); λmax(CHCl3)/nm 283;
᎐
᎐
δH (200 MHz; CDCl3) 1.1 (3H, t, J1,2 = 7 Hz, -NCH2CH3), 2.38
(3H, s, -CH3), 3.35 (2H, q, J1,2 = 7 Hz, -NCH2CH3), 6.10 (1H,
d, J1,2 = 16 Hz, -NCOCH᎐CHPh), 7.06–7.33 (4H, m, Ph) and
᎐
7.55–7.78 (2H, d and m, J1,2 = 16 Hz, -NCOCH᎐CHPh, Ph);
δC (50 MHz; CDCl3) 21.03 (q), 36.83 (q), 99.89, 118.65, 128.33,
129.32, 129.94, 131.08, 135.64, 140.64, 140.96, 142.73, 143.50
᎐
Radical cyclisation of 1f with tributystannyl deuteride
A mixture of 1e (1.0 × 10Ϫ2 mol), tributylstannyl deuteride
(1.5 × 10Ϫ2 mol) and AIBN (3.5 × 10Ϫ4 mol) was refluxed in
toluene under an inert atmosphere for 10 h. The toluene was
and 166.43 (C᎐O); m/z 265 (40%), 264 (100), 236 (18), 131 (70),
᎐
103 (55) and 77 (24).
1162
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166

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N-(2-Iodo-4-methylphenyl)-N-benzylcinnamide, 1f
N-(2-Iodophenyl)-N-benzylcinnamide, 1k
Starting from 5.0 g of 2-iodo-4-methylaniline, 7.8 g of 1f were
obtained (80%); mp 157–158 ЊC (methanol); νmax(KBr)/cmϪ1
Starting from 5.0 g of 2-iodoaniline, 8.4 g of 1k were obtained
(80%); mp 88–89 ЊC (hexane); νmax(CHCl3)/cmϪ1 1664 vs (conj.
1651 vs (conj. C᎐O) and 1616 vs (conj. C᎐C); λmax(CHCl3)/nm
C᎐O) and 1619 vs (conj. C᎐C); λmax(CHCl3)/nm 280; δH (200
᎐ ᎐
᎐
᎐
282; δH (200 MHz; CDCl3) 2.34 (3H, s, -CH3), 4.05 (1H, d,
J1,1Ј = 16 Hz, -NCH2Ph), 5.70 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph),
MHz; CDCl3) 4.35 (1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 5.55
(1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 6.10 (1H, d, J1,2 = 16 Hz,
6.03–6.20 (1H, d, J1,2 = 16 Hz, -NCOCH᎐CHPh), 6.65 (1H,
-NCOCH᎐CHPh), 6.95–7.10 (1H, m, Ph), 6.93–7.10 (1H, m,
᎐
᎐
d, J1,3 = 3 Hz, Ph), 7.05 (1H, m, Ph), 7.26–7.28 (10H, m, Ph)
Ph), 7.36 (11H, m, Ph), 7.50–7.58 (2H, m, Ph), 7.71–7.84 (1H,
and 7.85 (2H, d, J1,2 = 16 Hz, -NCOCH᎐CHPh); δ (50 MHz;
d, J1,2 = 16 Hz, -NCOCH᎐CHPh) and 7.99–8.04 (1H, m, Ph);
᎐
᎐
C
CDCl3) 20.54 (q), 51.96 (t), 100.26, 119.50, 127.44, 127.87,
128.31, 128.57, 129.44, 129.52, 129.89, 130.54, 135.10, 137.00,
δC (50 MHz; CDCl3) 52.76, 117.45, 125.50, 127.74, 127.86,
128.49, 128.62, 129.21, 129.47, 129.80, 132.54, 133.72, 134.68,
140.18, 140.52, 140.83, 142.79 and 165.81 (C᎐O).
134.86, 136.38, 143.64, 147.21 and 165.52 (C᎐O); m/z 438 (10),
᎐
᎐
312 (62), 180 (21), 131 (70), 103 (57), 91 (100) and 77 (45);
HRMS: calculated: 442.06612 observed: ion not seen.
N-(2-Iodo-4-chlorophenyl)-N-methylcinnamide, 1g
Starting from 5.0 g of 2-iodo-4-chloroaniline, 5.1 g of 1g were
obtained (70%); mp 122–123 ЊC (hexane); νmax(CHCl3)/cmϪ1
N-(2-Iodo-4-methylphenyl)-N-benzyl(ꢀ-deuterio)cinnamide, 1l
Starting from 1.0 g of (α-deuterio)cinnamic acid 1.72 g of 1l
were obtained (80%); mp 110–111 ЊC (methanol); νmax(CHCl3)/
cmϪ1 1651 (C᎐O) and 1616 (C᎐C); λmax(CHCl3)/nm 282; δH (200
1667 vs (conj. C᎐O) and 1628 vs (conj. C᎐C); λmax(CHCl3)/
᎐
᎐
nm 280; δH (200 MHz; CDCl3) 3.50 (3H, s, -NCH3), 6.30
(1H, d, J1,2 = 16 Hz, -NCOCH᎐CHPh), 7.37–7.54 (6H, m, Ph),
᎐
᎐
᎐
MHz; CDCl3) 2.20 (3H, s, -CH3), 4.00 (1H, d, J1,1Ј = 14 Hz,
-NCH2Ph), 5.67 (1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 6.65 (0.15H,
7.64–7.54 (2H, d, J1,2 = 7 Hz, Ph), 7.86–7.90 (1H, d, J1,2
=
16 Hz, -NCOCH᎐CHPh) and 8.18 (1H, d, J1,4 = 1 Hz);
᎐
d, J1,2 = 16 Hz, -NCOCH᎐CHPh, isotopic impurity), 6.65
δC (50 MHz; CDCl3) 36.30 (q), 100.09, 117.56, 127.91, 128.66,
᎐
(1H, d, J1,2 = 7 Hz, Ph), 6.94 (1H, dd, J1,2 = 7 Hz, J1,3 = 3 Hz,
Ph), 7.10–7.35 (10H, m, Ph) and 7.70 (2H, m, Ph and
-NCOCH᎐CHPh ); δ (50 MHz; CDCl3) 20.54 (q), 51.96 (t),
100.26, 118.24, 119.50, 127.44 (d), 127.87 (d), 128.31 (d), 128.57
(d), 129.44 (d), 129.52 (d), 129.89 (d), 130.54 (d), 135.10,
129.73, 129.92, 130.07, 134.65, 134.86, 139.50, 142.95, 144.43
and 165.67 (C᎐O). HRMS calculated: 396.972895, observed:
᎐
396.972282.
᎐
C
N-(2-Iodo-4-chlorophenyl)-N-benzylcinnamide, 1h
137.00, 140.18, 140.52 (d), 140.83, 142.79 (d) and 165.81 (C᎐O);
᎐
Starting from 5.0 g of 2-iodo-4-chloroaniline, 7.0 g of 1h were
obtained (70%); mp 108–109 ЊC (hexane); νmax(CHCl3)/cmϪ1
m/z 454 (10%), 327 (54), 132 (62), 104 (15) and 91 (100).
1667 vs (conj. C᎐O), 1622 vs (conj. C᎐C); λmax(CHCl3)/nm 284;
᎐
᎐
N-(2-Iodo-4-methylphenyl)-N-benzyl(2-phenyl)cinnamide, 1n
δH (200 MHz; CDCl3) 4.05 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph),
5.75 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph), 5.97–6.05 (1H, d, J1,2
16 Hz, -NCOCH᎐CHPh), 6.70 (1H, d, J1,2 = 7 Hz, Ph), 7.25–
Starting from 5.0 g of 2-iodo-4-methylaniline, 8.57 g of 1n
were obtained (75%); mp 110–111 ЊC (hexane); νmax(CHCl3)/
cmϪ1 1638 br (conj. C᎐O and conj. C᎐C); λmax(CHCl3)/nm 290;
=
᎐
᎐
᎐
7.40 (12H, m, Ph), 7.80 (1H, d, J = 16 Hz, -NCOCH᎐CHPh)
᎐
δH (200 MHz; CDCl3) 2.25 (3H, s, -CH3), 4.24 (1H, d, J1,1Ј
=
and 8.00 (1H, d, J1,3 = 2 Hz, Ph); δC (50 MHz; CDCl3)
51.80 (t), 100.99, 117.63, 127.70, 127.94, 128.44, 128.67,
129.34, 129.44, 131.54, 134.76, 134.83, 136.56, 139.52, 142.21,
16 Hz, -NCH2Ph), 5.75 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph), 6.14
(1H, d, J1,2 = 7 Hz, Ph), 6.68 (1H, m, 1H, J1,2 = 7 Hz, J1,3 = 3 Hz,
Ph), 6.75–7.38 (15H, m, Ph) and 7.74 (1H, d, J1,3 = 3 Hz, Ph);
δC (50 MHz; CDCl3) 20.27 (q), 51.95 (t), 99.83, 127.35 (d),
127.49 (d), 127.76 (d), 128.05 (d), 128.19 (d), 128.70 (d), 128.80
(d), 129.26 (d), 129.35 (d), 131.27 (d), 132.99 (d), 135.41,
136.78, 138.08, 139.12, 139.91 (d), 140.46 and 170.81.
143.60 and 165.49 (C᎐O); m/z 473 (4%), 131 (20), 103 (8) and
᎐
91 (100).
N-(2-Iodo-4-bromophenyl)-N-benzylcinnamide, 1i
Starting from 5.0 g of 2-iodo-4-bromoaniline, 6.2 g of 1i were
obtained (70%); mp 126–127 ЊC (hexane); νmax(CHCl3)/cmϪ1
N-(4-Methylphenyl)-N-methylcinnamide, 6d
1648 vs (conj. C᎐O) and 1603 s (conj. C᎐C); λmax(CHCl3)/nm
᎐
᎐
Mp 76–77 ЊC (hexane); νmax(CHCl3)/cmϪ1 1607 vs (conj. C᎐O)
᎐
280; δH (200 MHz; CDCl3) 4.05 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph),
5.75 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph), 5.97–6.05 (1H, d, J1,2 = 16
and 1600 vs (conj. C᎐C); λmax(CHCl3)/nm 280; δH (200 MHz;
᎐
CDCl3) 2.25 (3H, s, -CH3), 3.30 (3H, s, -CH3), 6.25 (1H, d,
Hz, -NCOCH᎐CHPh), 6.60 (d, 1H, J1,2 = 7 Hz, Ph), 7.25–7.40
᎐
J1,2 = 16.0 Hz, -NCOCH᎐CHPh), 6.75–7.40 (9H, m, Ph) and
᎐
(12H, m, Ph), 7.80 (1H, d, J1,2 = 16 Hz, -NCOCH᎐CHPh) and
᎐
7.50 (d, J1,2 = 16.0 Hz, -NCOCH᎐CHPh); δ (50 MHz; CDCl )
᎐
C
3
8.12 (1H, d, J1,3 = 2 Hz, Ph); δC (50 MHz; CDCl3) 51.73 (t),
101.49, 117.57, 122.73, 127.67, 127.92, 128.44, 128.64, 129.40,
129.78, 131.94, 132.29, 134.78, 136.52, 142.18, 142.65, 143.58
21.01, 37.60, 118.68, 126.95, 127.77, 128.56, 129.40, 130.16,
135.11, 137.48, 140.84, 141.63 and 166.33; m/z 250 (2%), 131
(76), 103 (80), 91 (14) and 77 (100).
and 165.36 (C᎐O); m/z 517 (2%), 131 (15), 103 (6) and 91 (100);
᎐
HRMS calculated: 516.95417, observed: 516.95586.
N-(4-Methylphenyl)-N-ethylcinnamide, 6e
N-(2-Iodophenyl)-N-methylcinnamide, 1j
Mp 54–55 ЊC (hexane); νmax(CHCl3)/cmϪ1 1607 vs (conj. C᎐O)
᎐
and 1600 vs (conj. C᎐C); λmax(CHCl3)/nm 280; δH (200 MHz;
᎐
Starting from 5.0 g of 2-iodoaniline, 5.9 g of 1j were obtained
(70%); mp 108–109 ЊC (hexane); νmax(CHCl3)/cmϪ1 1654 vs
CDCl3) 1.05 (3H, t, J1,2 = 7 Hz, -NCH2CH3), 2.25 (3H, s, -CH3),
3.76 (2H, q, J1,2 = 7 Hz, -NCH2CH3), 6.10 (1H, d, J1,2 = 14 Hz,
(conj. C᎐O) and 1610 vs (conj. C᎐C); λmax(CHCl3)/nm 280;
᎐
᎐
-NCOCH᎐CHPh), 6.95 (2H, d, J1,2 = 7 Hz, Ph), 7.15 (7H, m,
᎐
δH (200 MHz; CDCl3), 3.2 (3H, s, -NCH3), 6.00 (1H, d, J1,2 = 15
Ph) and 7.58 (1H, d, J1,2 = 14 Hz, -NCOCH᎐CHPh); δ (50
᎐
C
Hz, -NCOCH᎐CHPh), 6.97–7.38 (9H, m, Ph), 7.60 (1H, d,
᎐
MHz; CDCl3) 13.05 (q), 21.10 (q), 44.45 (t), 119.31, 127.81,
128.15, 128.61, 129.33, 130.17, 135.38, 137.64, 139.31, 141.47
J1,2 = 15 Hz, -NCOCH᎐CHPh) and 7.85 (1H, d, J1,2 = 7 Hz,
᎐
Ph); δC (50 MHz; CDCl3) 26.16 (q), 117.87 (d), 127.68 (d),
127.93 (d), 128.46 (d), 128.67 (s), 129.28 (d), 129.42 (s), 129.78
(d), 134.86 (s), 140.02 (d), 142.29 (d), 145.41 (s) and 165.65
and 165.69 (C᎐O); m/z 250 (2%), 131 (76), 103 (80), 91 (14) and
᎐
77 (100).
(C᎐O); m/z 364 (2), 237 (18), 236 (100), 208 (10), 131 (88), 103
(18) and 77 (14); HRMS: calculated: 364.019662, observed:
364.017677.
᎐
N-(4-Chlorophenyl)-N-methylcinnamide, 6g
Mp 77–78 ЊC (hexane); νmax(CHCl3)/cmϪ1 1630 vs (conj. C᎐O);
᎐
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166
1163

View Article Online
δH (200 MHz; CDCl3) 3.45 (3H, s, -CH3), 6.25 (1H, d, J1,2 = 16.0
Hz, -NCOCH᎐CHPh ), 7.15–7.40 (9H, m, Ph) and 7.58 (1H, d,
47.03 (d), 109.85 (d), 124.76 (d) 126.75 (d), 126.80 (d), 127.40
(d), 127.77 (d), 128.33 (d), 128.64 (d), 129.54 (d), 129.56,
᎐
J1,2 = 16.0 Hz, -NCOCH᎐CHPh); δ (50 MHz; CDCl3) 37.52,
118.26, 127.86, 128.58, 128.70, 129.66, 129.80, 133.29, 135.00,
129.77, 134.98 (d), 136.69, 141.87 and 176.21 (C᎐O); m/z
348 (3%), 346 (10), 131 (100), 103 (57) and 91 (78); HRMS:
calculated: 347.107715, observed: 347.108165.
᎐
᎐
C
142.22, 142.30 and 166.02 (C᎐O).
᎐
1,5-Dimethyl-3-benzylindolin-2-one, 7d
1,3-Dibenzyl-5-bromoindolin-2-one, 7i
0.50 g of 1d were electrolysed; mp 91–92 ЊC (hexane);
0.50 g of 1i were electrolysed; mp 114–115 ЊC (hexane);
νmax(CHCl3)/cmϪ1 1699 vs (C᎐O); λmax(CHCl3)/nm 260; δH (200
νmax(CHCl3)/cmϪ1 1724 vs (conj. C᎐O); λmax(CHCl3)/nm 267;
᎐
᎐
MHz; CDCl3) 2.21 (3H, s, -CH3), 2.77–2.92 (1H, dd, J1,1Ј = 13,
J1,2 = 8 Hz, -CHCH2Ph), 3.12 (3H, s, -NCH3), 2.86 (1H,
dd, J1,1Ј = 13, J1,2 = 4 Hz, -CHCH2Ph), 3.69 (1H, dd, J1,2 = 4,
J1,2 = 8 Hz, -CHCH2Ph), 6.65 (2H, m, Ph) and 6.93–7.30 (6H,
m, Ph); δC (50 MHz; CDCl3) 21.04 (q), 26.08 (q), 36.81 (t), 47.07
(d), 107.52 (d), 125.38 (d), 126.54, 127.88, 128.42 (d), 128.87
δH (200 MHz; CDCl3) 3.10–3.20 (1H, dd, J1,1Ј = 14, J1,2 =
8 Hz, -CHCH2Ph), 3.40–3.59 (1H, dd, J1,1Ј = 14, J1,2 = 4 Hz,
-CHCH2Ph), 3.80–3.85 (1H, dd, J1,2 = 8, J1,2 = 4 Hz, -CHCH2-
Ph), 4.57 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph), 6.37 (1H, d, J1,1Ј = 16
Hz, -NH2Ph), 6.37 (1H, d, J1,2 = 7 Hz, Ph), 6.88 (2H, m, Ph),
and 7.08–7.34 (11H, m, Ph); δC (50 MHz; CDCl3) 36.23 (t),
43.53 (d), 47.02 (t), 110.40 (d), 114.80, 125.80 (d), 126.79 (d),
127.44 (d), 127.57 (d), 128.36 (d), 128.67 (d), 129.58 (d), 130.21,
(d), 129.37 (d), 131.42 (d), 138.03, 141.80 and 176.94 (C᎐O);
᎐
m/z 251 (65%), 174 (4), 160 (100), 91 (20) and 77 (6). HRMS:
calculated: 251.131015, observed: 251.131085.
130.72 (d), 134.98, 136.72, 142.40 and 176.14 (C᎐O); m/z 393
᎐
(20%), 391 (20), 302 (10), 302 (10), 187 (10) and 91 (100);
HRMS: 391.0577 observed: 391.058843.
1-Ethyl-3-benzyl-5-methylindolin-2-one, 7e
0.50
g of 1e were electrolysed; mp 65–66 ЊC (hexane);
1-Methyl-3-benzylindolin-2-one, 7j
νmax(CHCl3)/cmϪ1 1715 br (conj. C᎐O); λmax(CHCl3)/nm 263;
᎐
δH (200 MHz; CDCl3) 1.00 (t, 3H, J = 7 Hz), 2.13 (s, 3H), 2.76–
2.93 (dd, 1H, J = 14 Hz, J = 7 Hz), 3.35 (dd, 1H, J = 14 Hz,
J = 5 Hz), 3.40–3.80 (m, 3H), (d ϩ s, 2H, J = 7 Hz) and 6.90–
7.20 (m, 6H); δC (50 MHz; CDCl3) 12.40 (q), 21.00 (q), 34.42 (t),
36.76 (t), 46.99 (d), 107.65 (d), 125.48 (d), 125.83 (d), 126.48 (d),
128.06 (d), 128.67, 129.45 (d), 131.21, 137.73, 140.91 and
0.50 g of 1j were electrolysed; mp 67–68 ЊC (hexane);
νmax(CHCl3)/cmϪ1 1705 vs (C᎐O); λmax(CHCl3)/nm 258; δH (200
᎐
MHz; CDCl3) 2.77–2.92 (1H, dd, J1,1Ј = 13, J1,2 = 8 Hz,
-CHCH2Ph), 3.12 (3H, s, -NCH3), 2.86 (1H, dd, J1,1Ј = 13,
J1,2 = 4 Hz, -CHCH2Ph), 3.69 (1H, dd, J1,2 = 4, J1,2 = 8 Hz,
-CHCH2Ph), 6.65 (2H, d, J1,2 = 7Hz, Ph), 6.85 (1H, t, J1,2 = 7,
J1,3 = 2 Hz, Ph) and 6.93–7.30 (6H, m, Ph); δC (50 MHz;
CDCl3) 26.05 (q), 36.78 (t), 47.00 (d), 107.84, 121.98, 124.47,
126.55, 127.88, 128.22, 128.34, 129.34, 137.90, 144.15, 177.01
176.50 (C᎐O); m/z 265 (80%), 188 (7), 174 (100), 146 (10),
᎐
91 (30) and 77 (7).
(C᎐O); m/z 237 (5%), 146 (12), 91 (100) and 77 (8).
᎐
1,3-Dibenzyl-5-methylindolin-2-one, 7f
0.50 g of 1f were electrolysed; mp 110–111 ЊC (hexane);
1,3-Dibenzylindolin-2-one, 7k
νmax(CHCl3)/cmϪ1 1718 vs (C᎐O); λmax(CHCl3)/nm 270; δH (200
᎐
MHz; CDCl3) 2.25 (3H, s, -CH3), 3.00–3.10 (1H, q, J1,1Ј = 14,
0.50 g of 1k were electrolysed; mp 98–99 ЊC (hexane);
J1,2 = 8 Hz, -CHCH2Ph), 3.40–3.59 (1H, dd, J1,1Ј = 14, J1,2
=
νmax(CHCl3)/cmϪ1 1718 br (C᎐O); λmax(CHCl3)/nm 263;
᎐
4 Hz, -CHCH2Ph), 3.40–3.50 (q, 1H, J1,2 = 8, J1,2 = 4 Hz,
-CHCH2Ph), 4.57 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph), 5.05 (1H, d,
J1,1Ј = 16 Hz -NCH2Ph), 6.37 (1H, d, J1,2 = 7 Hz, Ph), 6.78 (4H,
m, Ph) and 7.08–7.34 (8H, m, Ph); δC (50 MHz; CDCl3) 21.02
(q), 36.04 (t), 43.45t), 47.07 (d), 108.68 (d), 119.49, 125.22 (d),
126.55 (d), 126.83 (d), 127.19 (d), 128.05 (d), 128.17 (d), 128.54
(d), 129.61 (d), 131.48, 135.59, 137.37, 140.95 and 176.78
δH (200 MHz; CDCl3) 3.00 (1H, dd, J1,2 = 13, J = 8 Hz,
-CHCH2Ph), 3.36–3.45 (1H, dd, J1,1Ј = 13, J1,2 = 4 Hz, -CHCH2-
Ph), 3.71–3.78 (1H, dd, J1,2 = 8, J1,2 = 4 Hz, -CHCH2Ph), 4.52
(1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 4.93 (1H, d, J1,1Ј = 14 Hz,
-NCH2Ph), 6.44 (1H, d, J1,2 = 7 Hz, Ph), 6.78–6.88 (4H, m,
J1,2 = 8, J1,3 = 3 Hz, Ph) and 6.94–7.25 (9H, m, Ph); δC (50 MHz;
CDCl3) 36.36 (t), 43.40 (t), 46.97 (d), 108.94 (d), 122.00 (d),
124.35 (d), 126.55 (d), 126.81 (d), 127.22 (d), 127.80 (d), 128.09,
128.18, 128.54 (d), 129.57 (d), 135.45, 137.27, 143.30 and
(C᎐O); m/z 327 (41%), 236 (63), 91 (100) and 77 (6); HRMS:
᎐
calculated: 327.162315, observed: 327.159564.
176.80 (C᎐O); m/z 313 (35%), 222 (50) and 91 (100); HRMS:
᎐
calculated: 313.146650, observed: 313.147285.
1-Methyl-3-benzyl-5-chloroindolin-2-one, 7g
0.50 g of 1g were electrolysed; mp 115–116 ЊC (hexane);
1,3-Dibenzyl-5-methyl-3-deuterioindolin-2-one, 7l
Mp 110–111 ЊC (hexane); νmax(CHCl3)/cmϪ1 1718 vs (C᎐O);
νmax(CHCl3)/cmϪ1 1721 vs (conj. C᎐O); λmax(CHCl3)/nm 260;
᎐
δH (200 MHz; CDCl3) 2.78–2.95 (1H, dd, J1,1Ј = 14, J1,2
=
᎐
8 Hz, -CHCH2Ph), 3.13 (3H, s, -NCH3), 3.37–3.51 (1H, dd,
J1,1Ј = 14, J1,2 = 7 Hz, -CHCH2Ph), 3.66–3.73 (1H, q, J1,2 = 8,
J1,2 = 4 Hz -CHCH2Ph), 6.63–6.80 (2H, m, Ph) and 7.11–
7.40 (6H, m, Ph); δC (50 MHz; CDCl3) 26.20 (q), 36.62 (t), 47.09
(d), 108.71 (d), 124.94 (d), 126.85 (d), 127.38, 127.83 (d), 128.39
(d), 129.29 (d), 129.93 and 137.29; m/z 273 (2.8%), 271 (9), 182
(4), 180 (12) and 91 (100); HRMS: calculated: 271.072423,
observed: 271.07176.
λmax(CHCl3)/nm 270; δH (200 MHz; CDCl3) 2.45 (3H, s, -CH3),
3.00 (1H, d, J1,1Ј = 14 Hz, -CDCH2Ph), 3.45 (1H, d, J1,1Ј = 14
Hz, -CDCH2Ph), 4.25 (1H, d, J1,1Ј = 13 Hz, -NCH2Ph), 4.50
(1H, d, J1,1Ј = 13 Hz, -NCH2Ph), 6.15 (1H, d, J1,2 = 7 Hz, Ph),
6.40 (1H, m, Ph), 6.8 (4H, m, Ph) and 7.1–7.4 (8H, m, Ph);
δC (50 MHz; CDCl3) 21.02 (q), 36.04 (-CDCH2Ph), 43.45 (t),
47.07 (d), 108.68 (d), 119.49, 125.22 (d), 126.55 (d), 126.83 (d),
127.19 (d), 128.05 (d), 128.17 (d), 128.54 (d), 129.61 (d), 131.48,
135.59, 137.37, 140.95 and 176.78 (C᎐O); m/z 328 (38%), 327
᎐
(38), 237 (27), 236 (38) and 91 (100).
1,3-Dibenzyl-5-chloroindolin-2-one, 7h
0.50 g of 1h were electrolysed; mp 120–121 ЊC (hexane);
1-Benzyl-3-(α-deuteriobenzyl)-5-methylindolin-2-one, 7m
Mp 110–111 ЊC (hexane); νmax(CHCl3)/cmϪ1 1718 vs (C᎐O);
λmax(CHCl3)/nm 270; δH (200 MHz; CDCl3) 2.25 (3H, s,
-CH3), 3.00 (0.5H, d, J1,2 = 7 Hz, -CHCHDPh), 3.45 (0.5H, d,
J1,2 = 7 Hz, -CHCHDPh), 3.85 (1H, m, J1,3 = 3, J1,2 = 7 Hz,
-CHCHDPh), 4.25 (1H, d, J1,1Ј = 13 Hz, -NCH2Ph), 4.50 (1H,
νmax(CHCl3)/cmϪ1 1718 vs (C᎐O); λmax(CHCl3)/nm 275; δH (200
᎐
MHz; CDCl3) 3.00–3.10 (1H, dd, J1,1Ј = 14, J1,2 = 8 Hz, -CHCH2-
Ph), 3.31–3.40 (1H, dd, J1,1Ј = 14, J1,2 = 4 Hz, -CHCH2Ph),
3.70–3.75 (1H, q, J1,2 = 8, J1,2 = 4 Hz, -CHCH2Ph), 4.47 (1H, d,
J1,1Ј = 16 Hz, -NCH2Ph), 6.32 (1H, d, J1,1Ј = 7 Hz, Ph) and 6.77–
7.25 (12H, m, Ph); δC (50 MHz; CDCl3) 36.16 (t), 43.49 (t),
᎐
1164
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166

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d, J1,1Ј = 13 Hz, -NCH2Ph), 6.15 (1H, d, J1,2 = 7 Hz, Ph), 6.40
(4H, m, Ph) and 7.25 (8H, m, Ph); δC (50 MHz; CDCl3) 21.02
(q), 36.04 (3 equally intense signals), 43.45 (t), 47.07 (d), 108.68
(d), 119.49, 125.22 (d), 126.55 (d), 126.83 (d), 127.19 (d), 128.05
(d), 128.17 (d), 128.54 (d), 129.61 (d), 131.48, 135.59, 137.37,
13 Hz, -C(OH)CH2Ph), 2.84 (1H, d, J1,1Ј = 13 Hz, -C(OH)-
CH2Ph), 4.05 (d, 1H, J1,1Ј = 16 Hz, -NCH2Ph), 4.31 (1H, d,
J1,1Ј = 16 Hz, -NCH2Ph), 6.01 (2H, m, Ph), 6.27 (2H, dd, J1,2 = 7,
J1,3 = 2 Hz, Ph), 6.38 (2H, d, J1,2 = 7 Hz, Ph), 6.57–6.7 (7H, m,
Ph) and 6.90 (1H, d, J1,3 = 2 Hz, Ph); δC (50 MHz; CDCl3) 42.42
(t), 43.13 (t), 76.67 (q), 110.32 (d), 124.58 (d), 125.36 (d),
126.31, 126.59 (d), 127.05 (d), 127.78 (d), 128.38 (d), 128.74 (d),
140.95 and 176.78 (C᎐O); m/z 328 (50%), 237 (28), 236 (60), 92
᎐
(23) and 91 (100); HRMS: calculated: 328.17614, observed:
328.17543.
130.09 (d), 132.51, 134.27, 135.32, 141.11 and 176.54 (C᎐O);
᎐
m/z 365 (5%), 363 (15), 274 (8), 272 (24) and 91 (100); HRMS:
calculated: 363.102105, observed: 363.10528.
1,3-Dibenzyl-3-phenyl-5-methylindolin-2-one, 7n
Mp 116–117 ЊC (hexane); νmax(CHCl3)/cmϪ1 1718 vs (conj.
C᎐O); λmax(CHCl3)/nm 282; δH (200 MHz; CDCl3) 2.25 (3H, s,
᎐
3-Hydroxy-1,3-dibenzyl-5-bromoindolin-2-one, 8i
-CH3), 3.45 (1H, d, J1,1Ј = 13 Hz, -CH2Ph), 3.85 (1H, d, J1,1Ј = 13
Hz, -CH2Ph), 4.40 (d, 1H, J1,1Ј = 16 Hz, -NCH2Ph), 4.80 (d, 1H,
J1,1Ј = 16 Hz, -NCH2Ph), 6.24 (1H, d, J1,2 = 7 Hz, Ph), 6.56 (2H,
t, J1,2 = 7, J1,3 = 3 Hz, Ph), 6.80 (3H, m, Ph) 6.94–7.14 (7H,
m, Ph), 7.17–7.32 (3H, m, Ph) and 7.46 (2H, t, J = 7 Hz, Ph);
δC (50 MHz; CDCl3) 21.9 (q), 43.37 (t), 43.64 (t), 58.37 (q),
109.11 (d), 125.98 (d), 126.56 (d), 126.63 (d), 127.00 (d), 127.06
(d), 127.19 (d), 127.35 (d), 127.76 (d), 128.41 (d), 128.45 (d),
128.60 (d), 130.42 (d), 131.44, 131.65, 135.34, 135.83, 140.56
0.50 g of 1i were electrolysed; mp 230–231 ЊC (CHCl3);
νmax(CHCl3)/cmϪ1 3328
w (OH) and 1715 vs (C᎐O);
᎐
λmax(CHCl3)/nm 260; δH (200 MHz; CDCl3) 2.61 (1H, d,
J1,1Ј = 13 Hz, -C(OH)CH2Ph), 2.90 (1H, d, J1,1Ј = 13 Hz,
-C(OH)CH2Ph), 4.04 (1H, d, J1,1Ј = 16 Hz, -NCH2Ph), 4.31 (d,
1H, J1,1Ј = 16 Hz, -NCH2Ph), 5.97 (2H, t, J1,2 = 7, J1,3 = 2 Hz,
Ph), 6.27 (2H, dd, J1,2 = 7, J = 3 Hz, Ph), 6.40 (2H, dd, J = 7,
2 Hz, Ph), 6.56–6.68 (6H, m, Ph), 6.79–6.84 (1H, dd, J = 7,
J = 3 Hz, Ph) and 6.95 (1H, d, J1,3 = 3 Hz, Ph); m/z 407 (10%),
405 (10), 315 (15), 313 (15), 131 (14) and 91 (100); HRMS:
calculated: 407.05209, observed: 407.05654.
and 177.57 (C᎐O); m/z 403 (10%), 312 (18), 237 (82), 160 (45),
᎐
131 (100), 117 (25), 103 (54) and 91 (62); HRMS: calculated:
403.193615, observed: 403.195804.
3-Hydroxy-1,3-dibenzylindolin-2-one, 8k
3-Hydroxy-3-benzyl-1,5-dimethylindolin-2-one, 8d
0.50 g of 1k were electrolysed; mp 178–179 ЊC (CHCl3);
νmax(CHCl3)/cmϪ1 3360 s (OH) and 1715 vs (C᎐O); λ
0.50 g of 1d were electrolysed; mp 139–140 ЊC (CCl4);
᎐
max
νmax(CHCl3)/cmϪ1 3376
w (O–H) and 1724 vs (C᎐O);
᎐
(CHCl3)/nm 260; δH (200 MHz; CDCl3) 3.15–3.45 (2H, AB q,
J1,1Ј = 13 Hz, -C(OH)CH2Ph), 4.08 (1H, br s, D2O exchanged,
-C(OH)CH2Ph), 4.31 (1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 4.89
(1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 6.36 (1H, d, J1,2 = 7 Hz), 6.59
(2H, d, J1,2 = 7 Hz, Ph), 6.85 (2H, d, J1,2 = 7 Hz, Ph), 6.95–7.21
(8H, m, Ph) and 7.24–7.33 (1H, m, Ph); δC (50 MHz; CDCl3)
43.68 (t), 44.73 (t), 77.66 (q), 109.54 (d), 122.96 (d), 124.39 (d),
126.60 (d), 126.84 (d), 127.25 (d), 128.02 (d), 128.60 (d), 129.34,
λmax(CHCl3)/nm 265; δH (200 MHz; CDCl3) 2.25 (3H, s, -CH3),
2.95 (3H, s, -NCH3), 3.10–3.40 (2H, ABq, J1,1Ј = 13 Hz, -C(OH)-
CH2Ph), 5.70 (1H, br s, D2O exchanged, -C(OH)CH2Ph),
6.50 (1H, d, 1H, J1,2 = 7 Hz, Ph) and 7.22 (7H, m, Ph); δC (50
MHz; CDCl3) 21.08 (q), 25.82 (q), 44.80 (t), 77.63 (q), 107.78
(d), 125.19, 125.60 (d), 127.52 (d), 129.49 (d), 129.52, 130.17
(d), 132.26 (d), 134.17, 140.62 and 178.19 (C᎐O); m/z 267
᎐
(12%), 176 (100) and 91 (18).
129.63 (d), 130.39 (d), 133.89, 134.85, 142.61 and 177.98 (C᎐O);
᎐
m/z 329 (5%), 312 (23.57), 238 (59.28), 237 (35.54) and 91 (100);
HRMS: calculated: 332.165055, observed: 332.165055.
3-Hydroxy-1,3-dibenzyl-5-methylindolin-2-one, 8f
0.50 g of 1f were electrolysed; mp 213–214 ЊC (CHCl3);
νmax(CHCl3)/cmϪ1 3328
s (O᎐H) and 1705 vs (C᎐O);
3-Acetoxy-1,3-dibenzyl-5-methylindolin-2-one, 9f
᎐ ᎐
λmax(CHCl3)/nm 269; δH (200 MHz; CDCl3) 2.25 (3H, s, -CH3),
3.25–3.44 (3H, AB q and s, J1,1Ј = 13 Hz, 1H, D2O exchanged,
-C(OH)CH2Ph), 4.41 (1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 4.95
(1H, d, J1,1Ј = 14 Hz, -NCH2Ph), 6.30 (1H, d, J1,2 = 7 Hz, Ph),
6.66 (2H, m, Ph), 6.92 (2H, m, Ph) and 7.1 (8H, m, Ph); δC (50
MHz; CDCl3) 21.06 (q), 43.69 (t), 44.82 (t), 76.36 (q), 109.30,
125.07, 126.63, 126.89, 127.24, 128.04, 128.59, 129.15, 129.96,
Mp 132–133 ЊC (hexane); νmax(CHCl3)/cmϪ1 1753 (C᎐O) and
᎐
1728 (C᎐O); λmax(CHCl3)/nm 264; δH (200 MHz; CDCl3) 2.07
᎐
(3H, s, -OCOCH3), 2.25 (3H, s, -CH3), 3.25 (2H, ABq, J1,1Ј
=
16 Hz, -C(OAc)CH2Ph), 4.74 (2H, d, J1,1Ј = 13 Hz, -NCH2Ph),
6.27 (1H, d, J1,1Ј = 7 Hz, Ph), 6.84–7.50 (12H, m, Ph); δC (50
MHz; CDCl3) 20.74, 21.05, 42.61, 43.87, 80.77, 109.18, 123.86,
126.68, 127.10, 127.86, 128.53, 129.94, 130.78, 131.84, 132.71,
135.38, 140.77, 168.74 and 174.11.
130.42, 132.53, 133.92, 135.02, 140.28 and 177.61 (C᎐O);
᎐
m/z 343 (18.8%), 251 (100) and 91 (94); HRMS: calculated:
343.157230, observed: 343.154184.
1,1Ј,5,5Ј-Tetramethyl-3,3Ј-dibenzyl-3,3Ј-biindoline-2,2Ј-dione,
11d
3-Hydroxy-1-methyl-3-benzyl-5-chloroindolin-2-one, 8g
Mp 240–241 ЊC (hexane); νmax(CHCl3)/cmϪ1 1696 vs (C᎐O);
᎐
0.50 g of 1g were electrolysed; mp 170–171 ЊC (CHCl3);
λmax(CHCl3)/nm 262; νmax(CHCl3)/cmϪ1 3532 w (OH) and 1721
λmax(CHCl3)/nm 268; δH (200 MHz; CDCl3) 2.20 (3H, s, -CH3),
3.52 (3H, s, -NCH3), 3.85 (1H, d, J1,1Ј = 13 Hz, -CCH2Ph), 4.18
(1H, d, J1,1Ј = 13 Hz, -C(OAc)CH2Ph), 6.12 (1H, d, J1,2 = 7 Hz,
Ph), 6.75 (1H, m, Ph) and 7.05 (6H, m, Ph); δC (50 MHz;
CDCl3) 20.99 (q), 25.34 (q), 35.06 (t), 57.48 (s), 106.54 (d),
124.56, 124.66 (d), 125.77, 127.15 (d), 127.99 (d), 128.19 (d),
vs (C᎐O); δ (200 MHz; CDCl3) 2.95 (3H, s, -NCH3), 3.24
᎐
H
(2H, AB q, J1,1Ј = 13 Hz, -C(OH)CH2Ph), 4.22 (1H, br s, D2O
exchanged, -C(OH)CH2Ph), 6.55 (1H, d, J1,2 = 6 Hz), 6.90 (2H,
m, Ph) and 7.15 (5H, m, Ph); δC (50 MHz; CDCl3) 26.00 (q),
44.87 (t), 77.62 (q), 109.12 (d), 124.94 (d), 127.00 (d), 127.82 (d),
128.28, 129.37 (d), 130.11 (d), 131.03, 133.46, 141.57 and
130.63 (d), 136.17, 140.62 and 176.78 (C᎐O); m/z 500 (8.21%),
᎐
251 (64.93), 250 (85), 222 (53.75) and 91 (100); HRMS:
calculated: 508.30898, observed: 508.305358.
177.67 (C᎐O); m/z 289 (3%), 287 (9), 197 (20), 196 (78), 195 (14)
᎐
and 91 (100); HRMS: calculated: 287.070805, observed:
287.067525.
1,1Ј,3,3Ј-Tetrabenzyl-5,5Ј-dimethyl-3,3Ј-biindoline-2,2Ј-dione,
3-Hydroxy-1,3-dibenzyl-5-chloroindolin-2-one, 8h
11f
0.50 g of 1h were electrolysed; mp 218–219 ЊC (CHCl3);
νmax(CHCl3)/cmϪ1 3350 w (OH) and 1718 vs (C᎐O); λ
Mp 144–145 ЊC (hexane); νmax(CHCl3)/cmϪ1 1720 (C᎐O),
λmax(CHCl3)/nm 268; δH (200 MHz; CDCl3) 2.25 (3H, s, -CH3),
3.85 (2H, d, J1,1Ј = 13 Hz, -CHCH2Ph), 4.25 (2H, AB q,
᎐
᎐
max
(CHCl3)/nm 264; δH (200 MHz; CDCl3) 2.65 (1H, d, J1,1Ј
=
J. Chem. Soc., Perkin Trans. 2, 2001, 1154–1166
1165

View Article Online
5281; (b) B. Burns, R. Grigg, V. Santhakumar, V. Sridharan,
J1,1Ј = 16 Hz, -NCH2Ph), 4.99 (1H, d, J1,1Ј = 13 Hz, -CCH2Ph),
5.85 (1H, d, J1,2 = 6 Hz, Ph), 6.62 (3H, d, J1,2 = 6 Hz, Ph) and
6.80–7.39 (9H, m, Ph); δC (50 MHz; CDCl3) 21.16 (q), 35.47 (t),
45.38 (t), 57.78 (s), 108.30 (d), 125.03 (d), 126.11 (d), 126.56 (d),
126.98 (d), 127.58 (d), 128.15 (s), 128.31 (d), 128.44 (d), 130.88
P. Stevenson and T. Worakun, Tetrahedron, 1992, 48, 7297.
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(d), 135.01 (s), 136.06 (s), 140.30 (s) and 176.76 (C᎐O); m/z M
᎐
(unobserved), 327 (58.62%), 326 (76.28), 146 (13.84) and 91
(100).
12 (a) P. G. Gassman, in Photoinduced Electron Transfer Part C.
Photoinduced Electron Transfer Reaction: Organic Substrates;
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Acknowledgements
M. R. is thankful to the management of the SPIC Science
Foundation, Chennai for their support. The authors thank
RSIC, IIT, Madras, Dr S. Narasimhan, Centre for Natural
Products, SPIC Science Foundation, Chennai for spectral data.
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