Reactions of 2-[(2-arylimino-2-cyano-1,1-dimethylethyl)arylamino]-3-methylbut-2-enenitrile with copper(II) acetate: Synthesis of 2-(2,3-dihydro-2,2-dimethyl-3-oxo-1H-indol-1-yl)-3-methylbut-2-enenitriles

Article abstract of DOI:10.1039/b207530j

Treatment of 2-[(2-arylimino-2-cyano-1,1-dimethylethyl)arylamino]-3-methylbut-2-enenitrile 15, prepared by reactions of N-aryl α-cyanoenamines 3 with Cu(OAc)₂·H₂O (2 equiv.) in the presence of pyridine (2 equiv.) in EtOH at reflux, and with Cu(OAc)₂·H₂O (1 equiv.) in HOAc at reflux gave 2-(2,3-dihydro-2,2-dimethyl-3-oxo-1H-indol-1-yl)-3-methylbut-2-enenitriles 11 in moderate to good yields.

Full text of DOI:10.1039/b207530j

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Reactions of 2-[(2-arylimino-2-cyano-1,1-dimethylethyl)arylamino]-
3-methylbut-2-enenitrile with copper(II) acetate: synthesis of
2-(2,3-dihydro-2,2-dimethyl-3-oxo-1H-indol-1-yl)-3-methylbut-
2-enenitriles
1
Sangmin Yun and Kyongtae Kim*
School of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742,
Korea. E-mail: kkim@plaza.snu.ac.kr.; Fax: 82 2874 8858; Tel: 82 2880 6636
Received (in Cambridge, UK) 1st August 2002, Accepted 13th September 2002
First published as an Advance Article on the web 7th October 2002
Treatment of 2-[(2-arylimino-2-cyano-1,1-dimethylethyl)arylamino]-3-methylbut-2-enenitrile 15, prepared by
reactions of N-aryl α-cyanoenamines 3 with Cu(OAc)2ؒH2O (2 equiv.) in the presence of pyridine (2 equiv.) in EtOH
at reflux, and with Cu(OAc)2ؒH2O (1 equiv.) in HOAc at reflux gave 2-(2,3-dihydro-2,2-dimethyl-3-oxo-1H-indol-1-
yl)-3-methylbut-2-enenitriles 11 in moderate to good yields.
Introduction
N-Alkyl-α-cyanoenamines 1 and N-methyl-N-phenyl-α-cyano-
enamines 2 have received considerable attention as starting
materials for the preparation of a variety of organic com-
pounds.1 Nevertheless, no radical reactions of 1 and 2 have been
reported. Recently we found that, unlike α-cyanoenamines 1
and 2,2 N-aryl α-cyanoenamines 3 were slowly autoxidized to
α-hydroperoxy-N-arylimidoyl cyanides 4 in either crystalline
or solution state in air.1 The mechanism for the formation
of hydroperoxides 4 is uncertain. A coupling between triplet
oxygen and a radical 5 formed by oxidation of 33 may be
envisaged as a possible route leading to 4. We were interested in
the generation of 5 and 6 since the coupling product formed
from 5 and 6 could be utilized as a new precursor for the prep-
aration of 1,2-dihydroindol-3-one derivatives which are useful
synthetic intermediates for the synthesis of biologically active
compounds.4
With this in mind, we examined the reactivity of 3 toward
Cu() acetate which is known as a good single electron oxidant5
under various reaction conditions. The results are described
herein.
Results and discussion
(i) In acetic acid at room temperature
Treatment of α-cyanoenamine 3a (R1 = R2 = Me, R3 = H, R4 =
Ph) with Cu(OAc)2ؒH2O (2 equiv.) in HOAc for 19 h at rt under
Scheme 1
a nitrogen atmosphere gave α-hydroperoxyimidoyl cyanide 4a
(7%), α-acetoxyimidoyl cyanide 7 (18%), α-anilinoimidoyl
cyanide 8 (10%), along with unreacted 3a (50%) (Scheme 1). In
order to trap any cationic intermediate which might cause the
formation of 7 and/or 8, the same reaction was carried out in
the presence of anisole6 in air. However, no anisole-derived
product was detected. Instead, hydroperoxide 4a (34%) which
was the only identifiable product, was obtained, together with
complex mixtures.
2360
J. Chem. Soc., Perkin Trans. 1, 2002, 2360–2369
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b207530j

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The formation of hydroperoxide 4a in different yields under
a nitrogen atmosphere and in air indicates the involvement
of oxygen. A single electron transfer from 3a by either self-
oxidation (vide infra) or from Cu(OAc)2ؒH2O, followed by
deprotonation would give radicals 5a (R1 = R2 = Me, Ar = Ph)
and 6a (R1 = R2 = Me, Ar = Ph), which would react with oxygen
to give 4a.
The formation of 7 and 8 may be rationalized by assuming an
intermediate 9 in which copper() acetate makes a complex on
the nitrogen radical center of 5a to give a Cu() intermediate
97 (Scheme 2). As a result the C᎐C double bond may be acti-
᎐
Scheme 2
Scheme 3
vated to give the acetoxy compound 7 via a pericyclic transition
state. On the other hand the reaction of the intermediate 9
with aniline would give anilino compound 8. Alternatively
nucleophilic attack of acetic acid and aniline on a cation 10,8
generated via oxidation of 5a and/or 6a by copper() acetate
might give 7 and/or 8, respectively.
an increase in the solubility of Cu(OAc)2ؒH2O.11 Therefore, it
was desirable to find better conditions giving rise to radicals 5a
and 6a in order to obtain 11a in a higher yield.
(iii) Solvent effects
For higher concentrations of 5 and 6, we chose non-acidic polar
solvents such as absolute EtOH, DMF, and DMSO wherein
Cu(OAc)2ؒH2O was more soluble than in HOAc. From the
reaction of 3a with Cu(OAc)2ؒH2O in such solvents were iso-
lated the head-to-head dimer 14a, head-to-tail dimer 15a,
and N-phenyl-2-hydroxy-2-methylpropionamide 16 (Scheme 4).
It is uncertain whether the intermediate cation 10 is directly
formed from either 5a or 6a, or via Cu() intermediate 9.
(ii) In acetic acid at reflux
The foregoing reaction was carried out at reflux in expectation
of a shorter reaction time. The reaction was allowed to proceed
until no spot corresponding to 3a was observed on TLC. Con-
trary to expectation, the reaction was not completed in a
shorter time. From the reactions having no anisole as a cation
trapping agent, were obtained 7 (6%), 2,3-dihydro-1H-indole
derivative 11a (8%), isobutyramide 12 (7%), acetanilide 13
(35%), and complex mixtures which were unidentifiable
(Scheme 3). Similarly, 7 (19%), 11a (2%), 12 (3%), 13 (38%),
and unidentifiable complex mixtures were obtained from the
reaction where anisole was added.
Amide 12 is envisaged to be formed by hydrolysis of 3a,
which is analogous to the formation of an amide by treatment
of 2-alkylaminoalk-2-enenitrile with anhydrous HCl in EtOH.9
The formation of 13 may be explained by the reaction of aniline
with Cu(OAc)2ؒH2O10 at reflux. The structure of 1,2-dihydro-
indol-3-one 11a was determined based on spectroscopic (1H
and 13C NMR, IR, MS) and analytical data. An examination
of the structure 11a suggested that the coupling of radicals 5a
and 6a, followed by an intramolecular cyclization, was
involved. From the reaction carried out in the presence of
anisole under the same conditions were obtained the same
products, 7, 11a, 12, and 13. However, no anisole-incorporating
product was detected.
Scheme 4
The quantities of 3a and Cu(OAc)2ؒH2O, solvent, temperature,
reaction times, and yields of 14a, 15a, and 16 are summarized
in Table 1.
Table 1 shows that compound 16 is formed in DMSO and in
wet or dried DMF. An independent experiment showed that
N-phenyl-2-methylpropionamide was inert to Cu(OAc)2ؒH2O
in DMF at 120 ЊC. However, Compound 3a underwent self-
oxidation in DMF at 120 ЊC to give 4a1 (Scheme 5), which was
monitored by TLC and GC–MS. Addition of Cu(OAc)2ؒH2O
The formation of 11a, albeit in low yield at reflux tempera-
ture may be due to an increase in the concentrations of 5a and
6a because it is expected that oxidation by Cu(OAc)2ؒH2O at an
elevated temperature is more favorable than at rt as a result of
J. Chem. Soc., Perkin Trans. 1, 2002, 2360–2369
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Table 1 Reactions of 3a with Cu(OAc)2ؒH2O in various solvents
Yielda (%)
Entry
3a/mmol
Cu(OAc)2ؒH2O/mmol
Solvent
T /ЊC
t/h
14a
15a
16
1
2
3
1.05
1.08
0.77
2.10
2.16
1.69
EtOH
DMF
Dried
DMF
DMSO
Reflux/Ar
120
120/Ar
48
24
24
36
41
19
25
15
12
0
27
32
4
1.29
2.84
120
24
37
0
28
a Isolated yields.
Table 2 Reactions of 3a with different concentrations of Cu(OAc)2 ؒH2O in EtOH
Yielda (%)
14a
Entry
3a/mmol
Cu(OAc)2ؒH2O/mmol
Additive
t/h
15a
17a
1
2
3
4
5
6
7
1.05
0.72
0.99
0.78
3.31
5.01
1.47
2.10
4.43
1.98
1.72
6.62
48
48
48
48
48
96
48
36
22
30
11
44
26
27
25b
21
20
10
34
30
22
Styrene
Hex-1-ene
Pyridine
Pyridine
7c
20
15.03
3.23d
a Isolated yields. b Unreacted 3a was recovered in 24% yield. c Unreacted 3a was recovered in 13% yield. d Mn(OAc)3 was used as an oxidant.
Table 3 Reactions of 3 with Cu(OAc)2ؒH2O in the presence of
pyridine
Yielda (%)
Scheme 5
Compound
R1
R2
Ar
t/h
14
15
17
(2 equiv. based on 3a) to the mixture produced by self-oxidation
gave 16 in 47% yield.
3a
3b
3c
3d
3e
3f
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Ph
48
60
48
24
24
22
12
22
48
48
a 44
b 21
c 24
d 34
e 37
f 37
g 15
h 25
i 20
j 0
a 34
b 34
c 35
d 8
e 31
f 33
g 0
h 17
i 29
j 41
a 7
b 24
c 18
Conversion of 4a into 16 may be explained by assuming a
complex formed by interaction between the imino nitrogen
of 4a and Cu(OAc)2ؒH2O acting as a Lewis acid,12 followed
by hydrolysis of the imidoyl cyanide complex to give an α-
hydroperoxyamide in which the O–O bond is readily cleaved by
the action of Cu(OAc)2ؒH2O to give 16. An analogous cleavage
of the O–O bond has been reported.7
4-ClC6H4
4-BrC6H4
2-MeC6H4
3-MeC6H4
4-MeC6H4
4-MeOC6H4
4-MeC6H4
Ph
3g
3hb
3i
–(CH2)5–
Et Et
3j
Ph
(iv) Concentrations of Cu(OAc)2ؒH2O
a Isolated yields. b A mixture of (E)-and (Z)-3h (1.2:1) was used.
Since ethanol was found to be a better solvent than any of the
other solvents tried for 15a, dependence of the yield of 15a with
respect to the concentrations of Cu(OAc)2 was examined in
EtOH. The results are summarized in Table 2. When the con-
centration of Cu(OAc)2ؒH2O increased from 2 equiv. (entry 1)
to 6 equiv. (entry 2), yields of both 14a and 15a decreased
somewhat. Addition of either styrene (entry 3) or hex-1-ene
(entry 4) to the solution of 3a containing Cu(OAc)2ؒH2O (2
equiv.), did not lead to the formation of a radical-incorporating
product. Yields of 14a and 15a increased to 44% and 34%,
respectively, when the reaction was carried out in the presence
of pyridine (2 equiv.), which was reported to increase the
oxidation potential of Cu()5a under the foregoing conditions.
Interestingly, compound 17a, which is envisaged to be formed
by the substitution of one of the cyano groups of 14a by an
ethoxy group, was formed in 7% yield (entry 5). The yield of
17a (20%) increased significantly at the expense of the yields
of 14a and 15a when a higher concentration of Cu(OAc)2ؒH2O
(3 equiv.) and a longer reaction time (96 h) was allowed
(entry 6). Use of Mn(OAc)3 13 in place of Cu(OAc)2ؒH2O as an
oxidant caused a decrease in the yields of 14a and 15a (entry 7).
We chose the conditions represented by entry 5 for other
reactions of cyanoenamines. Reaction times and yields of 14,
15, and 17 are summarized in Table 3.
and 2-Me (24 h) have shorter reaction times compared with
those with an electron-withdrawing group on the Ar, i.e., 4-Cl
(60 h), and 4-Br (48 h). Moreover, in the case of the Ar having
an electron-withdrawing group, compounds 17b,c were formed
in comparable yields to those of 14b,c, respectively. The result
indicates that the yields of 17 increase with the reaction times.
In addition, it is noteworthy that when R1 = R2 = Et, no head-
to-head product 14j is formed. This must be due to the severe
steric hindrance arising from two ethyl groups of 5 (R1 = R2 =
Et). In contrast, no head-to-tail product 15g was detected. This
might be due to the instability of radicals 5g (R1 = R2 = Me, Ar
= 4-MeOC6H4) and 6g (R1 = R2 = Me, Ar = 4-MeOC6H4) and/or
dimers 14g and 15g, which have an electron-donating group, in
view of the relatively short reaction time (12 h) and a lower
yield of 14g compared with those of other head-to-head
dimers.
Table 3 shows that the reactions of 3 bearing an electron-
donating group on the Ar group, i.e., 3-Me (24 h), 4-Me (22 h),
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Attempts to separate a mixture of stereoisomers 3h (E:Z =
1.2:1) were unsuccessful. Their reaction afforded a mixture of
diastereomers 14h and 15h, respectively, which were inseparable
by column chromatography. However, the structures of dia-
stereomeric mixtures of 14h and 15h together with the ratios of
diastereomers 14h and 15h, were determined based on 1H NMR
and high resolution mass spectroscopy (vide infra).
the presence of Cu(OAc)2ؒH2O indicates the importance of
Cu(OAc)2ؒH2O as a Lewis acid catalyst. When the aryl group
has a 3-Me group on it, regioisomers 11e(I) and 11e(II) were
obtained in 14% and 58% yields, respectively. The predominant
formation of 11e(II) rather than 11e(I) may be due to the lesser
steric interaction in the course of the cyclization. When one
of the R groups is an ethyl group (R2 = Et), a longer reaction
time was required than with R2 = Me, presumably due to the
steric hinderance. It took 48 h for the reaction of 15j which has
two ethyl groups. This indicates the significance of the steric
hindrance.
To the best of our knowledge, this type of compound 11 has
never been reported although several methods of synthesizing
1,2-dihydroindol-3-ones are known.14 1,2-Dihydroindol-3-ones
are an important class of organic compound because not only
have they been utilized as intermediates for the synthesis of
various biologically active compounds such as indomethacin,15
tryptamin,16 ellipticine,17 but also some natural products,
i.e., austamide18 and brevianamide19 consist of this skeleton.
There have been numerous methods for the synthesis of 1,2-
dihydroindol-3-ones which comprise mainly the cyclization of
alkyl o-azidoaryl ketones under the basic conditions,20 the
reaction of 2-phenylindol-3-one with a Grignard reagent,21 and
MCPBA mediated oxidation of 1-substituted 3-formyl-1H-
indoles.22 In summary, it has been found that the title com-
pound 8 undergoes an intramolecular cyclization, analogous to
a Friedel–Craft acylation, in the presence of copper() acetate
in HOAc at reflux to give 1,2-dihydro-2,2-dimethylindol-3-ones
having an α-cyanoisobutenyl group at N-1 of the indol-3-ones.
It would appear worthwhile to explore further the synthetic
utility of 1,2-dihydroindol-3-ones, and such research is
currently in progress.
(v) Cyclization of head-to-tail dimers 15
Compound 11a was obtained from the reaction of 3a with
Cu(OAc)2ؒH2O in HOAc at reflux under an argon atmosphere.
In order to gain information about the mechanistic pathway,
compounds 14a and 15a were subjected to the same reaction
conditions. Interestingly, treatment of 14a with Cu(OAc)2ؒH2O
(1.1 equiv.) in HOAc at reflux gave inseparable unknown
mixtures, whereas compound 15a under the same conditions as
for 14a afforded 2-(2,3-dihydro-2,2-dimethyl-3-oxo-1H-indol-
1-yl)-3-methylbut-2-enenitrile 11a in 75% yield. The same
reaction in the presence of AlCl3 (2.0 equiv.) instead of Cu(OA-
c)2ؒH2O in benzene at rt afforded 11a and imino compound 18
in 12% and 35% yields, respectively (Scheme 6).
Experimental
1
The H and 13C NMR spectra were recorded at 300 and 75
MHz, respectively, for samples in CDCl3 solution containing
tetramethylsilane as internal standard: J-values are given in Hz.
IR spectra were recorded for KBr discs or thin-film samples
on KBr plates. Mass spectra were obtained by electron impact
at 70 eV, unless otherwise specified. Elemental analyses
were determined by the National Center for Inter-University
Research Facilities, Seoul National University. Column
chromatography was performed using silica gel (Merck, 70–230
mesh ASTM). Mps were determined on a Fisher-Johns
melting-point apparatus and are uncorrected. α-Chloroalkyl-
aldehydes23 and α-chloroaldimines24 were prepared according
to literature precedures.
General procedure for the synthesis of 3-alkyl-2-arylaminoalk-2-
enenitriles 3
To a solution of α-chloroaldehyde (38–84 mmol) in CCl4
(20 cm3) were added aniline derivatives (38–84 mmol) and
potassium carbonate (23–91 mmol). The mixture was stirred for
12 h at rt and then heated for 1 h at reflux. The cooled reaction
mixture was filtered to remove the solid which was washed with
CH2Cl2 (50 × 3 cm3). The filtrate was concentrated, followed
by addition of CH3CN (120–150 cm3). Potassium cyanide
(115–224 mmol) was added to the solution, which was heated
for 8–13 h at reflux. The cooled reaction mixture was filtered
and then washed with CH2Cl2. Removal of the solvent in vacuo
gave a brown liquid, which was chromatographed on a silica gel
column (2 × 20 cm) using a mixture of n-hexane and EtOAc
(5:1) to give the title compound.
Scheme 6
In order to ascertain the generality of the transformation of
15 into 11, compound 15 was subjected to the conditions under
which compound 11a was obtained (Scheme 6). In contrast
to the reactions of 14, which gave rise to complex mixtures,
reactions of compounds 15b–j under the same conditions
afforded 3-alkyl-2-(2,2-dialkyl-2,3-dihydro-3-oxo-1H-indol-1-
yl)alk-2-enenitriles 11b–j in good yields except for 15j (R1 = R2 =
Et). Quantities of reactants, reaction times, and yields of 11 are
summarized in Table 4.
3-Methyl-2-phenylaminobut-2-enenitrile 3a. 2-Chloro-2-
methylpropionaldehyde (6.38 g, 59.3 mmol) was treated with
aniline (5.52 g, 59.3 mmol) in the presence of K2CO3 (9.84 g,
71.2 mmol) in CCl4, followed by addition of KCN (7.73 g, 118.6
The reactions of compound 15a in the presence (1.1–1.8
equiv.) and in the absence of Cu(OAc)2ؒH2O gave 11a in
75% and 56% yields, respectively. The higher yield of 11a in
J. Chem. Soc., Perkin Trans. 1, 2002, 2360–2369
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Table 4 Quantities of reactants, reaction times, and yields of 11
Compound
R1
R2
X
mmol
Cu(OAc)2ؒH2O/mmol
t/h
14
30
28
14
14
6
Compound
11 Yielda (%)
15a
15a
15c
15b
15d
15e
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
H
4-Br
4-Cl
2-Me
3-Me
0.48
0.80
0.17
0.36
0.19
0.69
0.53
0
0.20
0.65
0.23
0.83
a (X = H)
a(X = H)
75
56
45
86
68
14
58
92
60b
15
b (X = 5-Br)
c(X = 5-Cl)
d (X = 7-Me)
e (I) (X = 4-Me)
e (II)(X = 6-Me)
f (X = 5-Me)
h (X = 5-Me)
j (X = H)
15f
15h
15j
Me
Me
Et
Me
Et
Et
4-Me
4-Me
H
0.38
0.20
0.33
0.46
0.24
0.40
4
30
480
a Isolated yields. b A mixture of (E)- and (Z)-stereoisomers.
mmol) in CH3CN (150 cm3). Work-up of the reaction mixture
in accordance with the above general procedure gave 3a (5.62 g,
55%).
CH3), 2.11 (3H, s, CH3), 3.74 (3H, s, OCH3), 4.65 (1H, br s,
NH), 6.67 (2H, d, J 8.9 Hz, ArH) and 6.83 (2H, d, J 8.9 Hz,
ArH); δC 19.06, 21.99, 55.68, 110.00, 114.88, 116.19, 122.82,
137.58, 147.18 and 153.94; m/z 202 (Mϩ, 91%), 187 (Mϩ – CH3,
100).
2-(4-Chlorophenylamino)-3-methylbut-2-enenitrile 3b. 2-
Chloro-2-methylpropionaldehyde (6.65 g, 61.8 mmol) was
treated with 4-chloroaniline (7.89 g, 61.8 mmol) in the presence
of K2CO3 (10.26 g, 74.2 mmol) in CCl4, followed by addition of
KCN (8.05 g, 123.6 mmol) in CH3CN (180 cm3). Work-up
of the reaction mixture in accordance with the above general
procedure gave 3b (5.62 g, 50%).
(E )- and (Z )-3-Methyl-2-(p-tolylamino)pent-2-enenitrile (E )-
and (Z )-3h. 2-Chloro-2-methylbutyraldehyde (4.98 g, 41.3
mmol) was treated with aniline (4.29 g, 40.0 mmol) in the
presence of K2CO3 (3.31 g, 24.0 mmol) in CCl4, followed by
addition of KCN (8.07 g, 123.9 mmol) in CH3CN (120 cm3).
Work-up of the reaction mixture in accordance with the above
general procedure gave a mixture of (E)- and (Z)-3h (4.45 g,
56%); liquid (Found: C, 77.9; H, 8.1; N, 13.9. C13H16N2 requires
C, 78.0; H, 8.05; N 14.0%); νmax (KBr)/cmϪ1 3352, 2960, 2920,
2208 and 1611; (Z)-isomer, δH 0.95 (3H, t, J 7.6 Hz, CH3), 2.05
(3H, d, J 1.2 Hz, CH3), 2.19 (3H, s, ArCH3), 2.26 (2H, q, J 7.6
Hz, CH2), 4.56 (1H, s, NH), 6.48–6.57 (2H, m, ArH) and 6.97
(2H, d, J 8.2 Hz, ArH); (E)-isomer, 1.10 (3H, t, J 7.5 Hz, CH3),
1.80 (3H, s, CH3), 2.19 (3H, s, ArCH3), 2.43 (2H, q, J 7.6 Hz,
CH2), 4.56 (1H, s, NH), 6.48–6.57 (2H, m, ArH) and 6.97 (2H,
d, J 8.2 Hz, ArH); m/z 200 (Mϩ, 97%), 185 (Mϩ – CH3, 100).
2-(4-Bromophenylamino)-3-methylbut-2-enenitrile 3c. 2-
Chloro-2-methylpropionaldehyde (8.37 g, 77.8 mmol) was
treated with 4-bromoaniline (13.39 g, 77.8 mmol) in the
presence of K2CO3 (6.45 g, 46.7 mmol) in CCl4, followed by
addition of KCN (15.20 g, 223.5 mmol) in CH3CN (230 cm3).
Work-up of the reaction mixture in accordance with the above
general procedure gave 3c (8.21 g, 42%).
3-Methyl-2-(o-tolylamino)but-2-enenitrile 3d. 2-Chloro-2-
methylpropionaldehyde (8.17 g, 76.0 mmol) was treated with o-
toluidine (8.14 g, 76.0 mmol) in the presence of K2CO3 (6.30 g,
45.6 mmol) in CCl4, followed by addition of KCN (9.90 g, 152.0
mmol) in CH3CN (230 cm3). Work-up of the reaction mixture
in accordance with the above general procedure gave 3d (8.06 g,
57%).
2-Anilino-2-cyclohexylideneacetonitrile 3i. 1-Chlorocyclo-
hexanecarbaldehyde (7.94 g, 54.2 mmol) was treated with
aniline (5.04 g, 54.2 mmol) in the presence of K2CO3 (4.49 g,
32.5 mmol) in CCl4, followed by addition of KCN (10.58 g,
162.5 mmol) in CH3CN (160 cm3). Work-up of the reaction
mixture in accordance with the above general procedure gave 3i
(6.52 g, 57%); mp 82–84 ЊC (from n-hexane–CH2Cl2) (Found:
C, 79.3; H, 7.6; N, 13.1. C14H16N2 requires C, 79.2; H, 7.6;
N, 13.2%); νmax (neat)/cmϪ1 3352, 2976, 2208 and 1629; δH 0.85
(3H, t, J 7.6 Hz, CH3), 1.02 (3H, t, J 7.6 Hz, CH3), 2.15 (2H, q,
J 7.6 Hz, CH2), 2.35 (2H, q, J 7.6 Hz, CH2), 4.68 (1H, s, NH),
6.53 (2H, d, ArH, J 7.5 Hz, ArH), 6.70 (1H, t, ArH, J 7.5 Hz,
ArH) and 7.07 (2H, td, ArH, J 7.5, 0.9 Hz, ArH); δC 11.77,
12.71, 22.78, 26.15, 107.86, 114.10, 116.25, 119.59, 129.08,
143.95 and 160.37; m/z 200 (Mϩ, 100%), 185 (Mϩ – CH3, 95).
3-Methyl-2-(m-tolylamino)but-2-enenitrile 3e. 2-Chloro-2-
methylpropionaldehyde (8.18 g, 76.1 mmol) was treated with m-
toluidine (8.15 g, 76.1 mmol) in the presence of K2CO3 (12.62 g,
91.3 mmol) in CCl4, followed by addition of KCN (9.90 g, 152.1
mmol) in CH3CN (230 cm3). Work-up of the reaction mixture
in accordance with the above general procedure gave 3e (7.51 g,
53%).
3-Methyl-2-(p-tolylamino)but-2-enenitrile 3f. 2-Chloro-2-
methylpropionaldehyde (9.09 g, 84.5 mmol) was treated with p-
toluidine (9.06 g, 84.5 mmol) in the presence of K2CO3 (7.01 g,
50.7 mmol) in CCl4, followed by addition of KCN (11.01 g,
169.0 mmol) in CH3CN (250 cm3). Work-up of the reaction
mixture in accordance with the above general procedure gave 3f
(9.13 g, 58%).
2-Anilino-3-ethylpent-2-enenitrile 3j. 2-Chloro-2-ethylbutyr-
aldehyde (5.16 g, 38.3 mmol) was treated with aniline (3.57 g,
38.3 mmol)in the presence of K2CO3 (3.18 g, 23.0 mmol) in
CCl4, followed by addition of KCN (7.48 g, 114.9 mmol)
in CH3CN (120 cm3). Work-up of the reaction mixture in
accordance with the above general procedure gave 3j (4.21 g,
54%); liquid (Found: C, 78.1; H, 8.1; N, 13.9. C13H16N2 requires
C, 78.0; H, 8.05; N, 14.0%); νmax (neat)/cmϪ1 3352, 2976, 2208
and 1629; δH 0.85 (3H, t, J 7.6 Hz, CH3), 1.02 (3H, t, J 7.6 Hz,
CH3), 2.15 (2H, q, J 7.6 Hz, CH2), 2.35 (2H, q, J 7.6 Hz, CH2),
4.68 (1H, s, NH), 6.53 (2H, d, J 7.5 Hz, ArH), 6.70 (1H, t, J 7.5
Hz, ArH) and 7.07 (2H, td, J 7.5, 0.9 Hz, ArH); δC 11.77, 12.71,
22.78, 26.15, 107.86, 114.10, 116.25, 119.59, 129.08, 143.95 and
160.37; m/z 200 (Mϩ, 100%), 185 (Mϩ – CH3, 95).
2-(4-Methoxyphenylamino)-3-methylbut-2-enenitrile 3g. 2-
Chloro-2-methylpropionaldehyde (7.43 g, 69.1 mmol) was
treated with p-anisidine (8.51 g, 69.1 mmol) in the presence
of K2CO3 (5.73 g, 41.5 mmol) in CCl4, followed by addition of
KCN (13.49 g, 207.1 mmol) in CH3CN (210 cm3). Work-up of
the reaction mixture in accordance with the above general
procedure gave 3g (7.26 g, 52%); liquid (Found: C, 71.2; H, 6.9;
N, 13.9. C12H14N2O requires C, 71.3; H, 7.00; N 13.85%);
νmax (neat)/cmϪ1 3352, 2910, 2224 and 1624; δH 1.87 (3H, s,
2364
J. Chem. Soc., Perkin Trans. 1, 2002, 2360–2369

View Article Online
Reaction of 3a with Cu(OAc)2
(5 cm3) under a nitrogen atmosphere was added anisole
(275 mg, 2.55 mmol) and Cu(OAc)2ؒH2O (463 mg, 2.55 mmol).
The mixture was heated for 24 h at reflux and then worked up
as before. Chromatography of the reaction mixture using a
mixture of n-hexane and EtOAc (5:1) gave 7 (51 mg, 19%),
unknown mixtures (32 mg), and a mixture of 11a and 12
(14 mg). Elution with the same solvent mixture (2:1) gave 13
(59 mg, 38%). Rechromatography (2 × 20 cm) of the mixture of
11a and 12 using a mixture of n-hexane and EtOAc (2:1) gave
12 (7 mg, 3%) and 11a (5 mg, 2%).
(i) Under a nitrogen atmosphere at rt. To a solution of 3a
(178 mg, 1.03 mmol) in HOAc (5 cm3) under a nitrogen atmos-
phere was added Cu(OAc)2ؒH2O (453 mg, 2.27 mmol). The
mixture was stirred for 19 h at rt, followed by addition of water
(30 cm3) and CH2Cl2 (30 cm3). The mixture was neutralized
with aqueous Na2CO3 and extracted with CH2Cl2 (30 × 2 cm3).
The combined extracts were dried over anhydrous MgSO4.
Removal of the solvent in vacuo gave a brown liquid, which was
chromatographed on a silica gel column (2 × 20 cm) using a
mixture of n-hexane and EtOAc (10:1) to give 2-cyano-1,1-
dimethyl-2-phenyliminoethyl acetate 7 (20 mg, 18%); liquid
(Found: C, 67.9; H, 6.0; N, 12.1. C13H14N2O2 requires C, 67.8;
H, 6.1; N, 12.2%); νmax (neat)/cmϪ1 2990, 2940, 2219, 1742,
1638, 1591, 1483, 1371, 1250, 1147, 1081, 1018, 781 and 699;
δH 1.64 (6H, s, 2 × CH3), 2.07 (3H, s, CH3) and 6.97–7.37 (5H,
m, ArH); δC 21.82, 24.96, 81.39, 110.37, 120.27, 127.55, 129.63,
147.54, 148.79 and 170.92; m/z 230 (Mϩ, 100%), 172 (58), 129
(75), 101 (42), 77 (72). Continuous elution with the same
solvent mixture gave 3-anilino-3-methyl-2-phenylimino-
butyronitrile 8 (12 mg, 10%): liquid (Found: C, 77.4; H, 6.4; N,
15.9. C17H17N3 requires C, 77.5; H, 6.5; N, 16.0%); νmax (neat)/
cmϪ1 2990, 2938, 2220, 1636, 1572, 1145 and 702; δH 1.69 (6H, s,
2 × CH3), 4.14 (1H, br s, NH), 6.69 (2H, d, J 7.8 Hz, ArH), 6.79
(1H, t, J 7.6 Hz, ArH), 6.68–7.08 (2H, m, ArH), 7.17 (2H, t,
J 7.5 Hz, ArH), 7.25–7.33 (1H, m, ArH) and 7.41 (2H, t, J 7.4
Hz, ArH); m/z 263 (Mϩ, 4%), 172 (3), 134 (100). Continuous
elution with the same solvent mixture gave unreacted 3a (87 mg,
50%) and 3-hydroperoxy-3-methyl-2-phenyliminobutyronitrile
4a (14 mg, 7%): mp 53–55 ЊC (from n-hexane–CH2Cl2) (Found:
C, 64.9; H, 6.1; N, 13.9. C11H12N2O2: C, 64.7; H, 5.9; N 13.7%);
νmax (neat)/cmϪ1 3250, 2990, 2224 and 1625; δH 1.63 (6H, s,
2 × CH3), 7.09 (2H, d, J 7.5 Hz, ArH), 7.32 (1H, t, J 7.4 Hz,
ArH), 7.44 (2H, t, J 7.4 Hz, ArH) and 8.86 (1H, br s, OOH);
δC 22.17, 84.96, 110.29, 120.05, 127.61, 129.26, 147.59 and
147.70.
Reaction of 3a with Cu(OAc)2ؒH2O in different solvents
(i) In EtOH. To a solution of 3a (180 mg, 1.05 mmol) in
EtOH (5 cm3) was added Cu(OAc)2ؒH2O (381 mg, 2.10 mmol)
under an argon atmosphere. The mixture was heated for 48 h
at reflux, followed by work-up as before. Chromatography
(2 × 20 cm) of the reaction mixture using a mixture of n-hexane
and EtOAc (10:1) as the eluent gave 3,3,4,4-tetramethyl-2,5-
bis(phenylimino)adiponitrile 14a (47 mg, 36%), 2-(2-cyano-N-
phenyl-2-phenylimino-1,1-dimethylethylamino)-3-methylbut-
2-enenitrile 15a (33 mg, 25%), and unreacted 3a (43 mg, 24%).
14a: mp 110–112 ЊC (from MeOH–H2O) (Found: C, 77.0;
H 6.4; N, 16.2. C22H22N4 requires C, 77.2; H, 6.50; N, 16.4%);
νmax (KBr)/cmϪ1 2211 and 1616; δH 1.49(12H, s, 4 × CH3) and
6.92–7.34 (10H, m, 2 × ArH); δC 23.38, 48.60, 111.60, 120.09,
127.46, 129.68, 149.13 and 149.99; m/z 342 (Mϩ, 47%), 341 (22),
327 (13), 250 (32), 213 (55), 172 (77), 171 (100).15a: liquid
(Found: C, 77.1; H, 6.4; N, 16.3. C22H22N4 requires C, 77.2; H,
6.5; N, 16.4%); νmax (neat)/cmϪ1 2207, 1632 and 1592; δH 1.68
(6H, s, 2 × CH3), 2.05 (3H, s, CH3), 2.12 (3H, s, CH3) and 6.89–
7.35 (10H, m, 2 × ArH); δC 22.85, 22.68, 23.91, 65.75, 111.93,
112.44, 118.57, 119.93, 122.12, 123.81, 126.30, 127.60, 129.75,
129.85, 145.19, 148.75, 150.33 and 158.77; m/z 342 (Mϩ, 30%),
341 (26), 327 (9), 250 (11), 213 (14), 172 (41), 171 (51), 155 (30),
144 (53), 77 (100).
(ii) In DMF. To a solution of 3a (186 mg, 1.08 mmol) in
DMF (10 cm3) was added Cu(OAc)2ؒH2O (381 mg, 2.16 mmol)
at rt. The mixture was heated for 24 h at 120 ЊC. Water (50 cm3)
was added to the cooled reaction mixture, which was then
extracted with CH2Cl2 (50 cm3 × 3) and EtOAc (50 cm3) in
a series. The combined organic layer was dried and worked up
as usual. Chromatography (2 × 20 cm) of the residue using
a mixture of n-hexane and EtOAc (10:1) gave 14a (74 mg, 41%)
and 15a (26 mg, 15%). Subsequent elution with the same
solvent mixture (3:1) gave 2-hydroxy-2-methyl-N-phenyl-
propionamide 16 (52 mg, 27%): liquid (Found: C, 67.1; H, 7.1;
N, 7.7. C10H13NO2 requires C, 67.0; H, 7.3; N, 7.8%); νmax
(neat)/cmϪ1 3263, 2974, 1653, 1441, 1185 and 1152; δH 1.47 (6H,
s, 2 × CH3), 2.73 (1H, br s, OH), 7.04 (1H, t, J 7.4 Hz, ArH),
7.25 (2H, t, J 7.6 Hz, ArH), 7.49 (2H, d, J 7.6 Hz, ArH) and
8.67 (1H, br s, NH); m/z 179 (Mϩ, 29%), 121 (45), 93 (100). The
same reaction of 3a (133 mg, 0.77 mmol) with Cu(OAc)2ؒH2O
(34 mg, 1.69 mmol) in dried DMF under an argon atmosphere
gave 14a (34 mg, 19%), 15a (21 mg, 12%), and 16 (62 mg, 32%).
(ii) In the presence of anisole in air at rt. To a solution of 3a
(342 mg, 2.00 mmol) in HOAc (10 cm3) was added anisole
(238 mg, 2.20 mmol) and Cu(OAc)2ؒH2O (453 mg, 2.27 mmol).
The mixture was stirred for 24 h at rt. The mixture was worked
up as described in (i). Chromatography of the reaction mixture
using a mixture of n-hexane and EtOAc (5:1) gave 4a (137 mg,
34%).
(iii) Under a nitrogen atmosphere at reflux. To a solution of
3a (210 mg, 1.22 mmol) in HOAc (5 cm3) under a nitrogen
atmosphere was added Cu(OAc)2ؒH2O (465 mg, 2.33 mmol).
The mixture was heated for 24 h at reflux and then worked up as
before. Chromatography (2 × 20 cm) of the reaction mixture
using a mixture of n-hexane and EtOAc (5:1) gave 7 (17 mg,
6%), unknown mixtures (40 mg), a mixture of N-phenyl-
isobutyramide 12 and 2-(2,3-dihydro-2,2-dimethyl-3-oxo-1H-
indol-1-yl)-3-methylbut-2-enenitrile 11a (45 mg). Elution with
the same solvent mixture (2:1) gave acetanilide 13 (58 mg, 35%).
Rechromatography (2 × 20 cm) of the mixture of 11a and 12
using a mixture of n-hexane and CH2Cl2 (2:1) gave 12 (14 mg,
7%) and 11a (23 mg, 8%): mp 60–62 ЊC (from n-hexane–
CH2Cl2) (Found: C, 75.0; H, 6.7; N, 11.7. C15H16N2O requires
C, 75.0; H, 6.7; N, 11.7%); νmax (neat)/cmϪ1 2210, 1707 and
1611; δH 1.22 (3H, s, CH3), 1.40 (3H, s, CH3), 1.82 (3H, s, CH3),
2.22 (3H, s, CH3), 6.56 (1H, d, J 8.2 Hz, ArH), 6.82 (1H, t, J 7.4
Hz, ArH), 7.44 (1H, t, J 7.2 Hz, ArH) and 7.61 (1H, d, J 7.6 Hz,
ArH); δC 20.54, 22.10, 22.54, 22.56, 69, 89, 105.91, 110.23,
116.44, 119.35, 119.70, 125.29, 137.61, 156.85, 159.99 and
202.74; m/z 240 (Mϩ).
(iii) In DMSO. From the reaction of 3a (222 mg, 1.29
mmol) with Cu(OAc)2ؒH2O (516 mg, 2.84 mmol) in DMSO
(10 cm3) at 120 ЊC were obtained 14a (83 mg, 37%) and 15a
(64 mg, 28%).
Reaction of 4a with Cu(OAc)2ؒH2O
A solution of 3a (186 mg, 1.05 mmol) in DMF (10 cm3) was
heated for 24 h at 120 ЊC by which time 3a was completely
converted into 3-hydroperoxy-3-methyl-2-phenyliminobutyro-
nitrile 4a. Cu(OAc)2ؒH2O (500 mg, 2.60 mmol) was added to
the mixture, which was then stirred for 18 h at 120 ЊC. Work-up
of the reaction mixture as described in (ii) gave 16 (101 mg,
47%).
(iv) In the presence of anisole under a nitrogen atmosphere
at reflux. To a solution of 3a (200 mg, 1.16 mmol) in HOAc
J. Chem. Soc., Perkin Trans. 1, 2002, 2360–2369
2365

View Article Online
General procedure for the reactions of 3 with Cu(OAc)2ؒH2O in
the presence of pyridine
N-(4-bromophenyl)-4-(4-bromophenylimino)-4-cyano-2,2,3,3-
tetramethylbutyrimidic acid ethyl ester 17c (81 mg, 18%).
14c: mp 193–194 ЊC (from n-hexane) (Found: C, 53.0; H,
4.3; N, 11.0. C22H20Br2N4 requires C, 52.8; H, 4.0; N, 11.2%);
νmax (KBr)/cmϪ1 2213 and 1617; δH 1.47 (12H, s, 4 × CH3), 6.80
(4H, d, J 8.7 Hz, 2 × ArH) and 7.44 (4H, d, J 8.7 Hz, 2 × ArH);
δC 22.83, 48.33, 110.90, 120.74, 121.40, 132.41, 147.34 and
150.15.
15c: mp 132–133 ЊC (from n-hexane–CH2Cl2) (Found: C,
52.8; H, 4.0; N, 11.0. C22H20Br2N4 requires C, 52.8; H, 4.0;
N, 11.2%); νmax (neat)/cmϪ1 2200 and 1626; δH 1.66 (6H, s, 2 ×
CH3), 2.03 (3H, s, ArCH3), 2.13 (3H, s, CH3), 6.81 (2H, d, J 8.7
Hz, ArH), 6.84 (2H, d, J 9.1 Hz, ArH), 7.32 (2H, d, J 9.1 Hz,
ArH) and 7.49 (1H, d, J 8.7 Hz, ArH); δC 20.33, 22.22, 23.38,
65.39, 111.07, 111.33, 116.07, 117.58, 120.96, 121.29, 122.59,
131.81, 132.43, 143.64, 146.74, 149.84 and 158.94.
To a solution of 3 (1.72–5.36 mmol) in absolute EtOH (15–
52 cm3) was added Cu(OAc)2ؒH2O (6.62–10.34 mmol) and
pyridine (6.62–10.34 mmol). The mixture was heated for an
appropriate time at reflux. Water (50 cm3) was added to the
cooled reaction mixture, which was then extracted with CH2Cl2
(50 cm3) and dimethyl ether (50 cm3 × 3). The combined organic
layers were dried (MgSO4). Removal of the solvent gave a
residue, which was chromatographed on silica gel (2 × 20 cm)
using a mixture of n-hexane and EtOAc (10:1) to give 14, 15,
and 17.
Reaction of 3a. Reaction of 3a (570 mg, 3.31 mmol) with
Cu(OAc)2ؒH2O (1.02 g, 6.62 mmol) in the presence of pyridine
(523 mg, 6.62 mmol) in EtOH (30 cm3) for 48 h gave 14a (217
mg, 44%), 15a (164 mg, 34%), 4-cyano-2,2,3,3-tetramethyl-N-
phenyl-4-phenyliminobutyrimidic acid ethyl ester 17a (41 mg,
7%), and unreacted 3a (75 mg, 13%).
17a: sticky solid (Found: C, 76.2; H, 7.4; N, 11.7. C23H27N3O
requires C, 76.4; H, 7.5; N, 11.6%); νmax (KBr)/cmϪ1 1637 and
1581; δH 0.52 (3H, t, J 7.1 Hz, OCH2CH3), 1.20 (6H, s, 2 ×
CH3), 1.29 (6H, s, 2 × CH3), 3.57 (2H, q, J 7.1 Hz, OCH2CH3),
6.53 (2H, d, J 7.6 Hz, ArH), 6.80 (2H, d, J 7.1 Hz, ArH) and
6.85–6.98 (2H, m, ArH), 7.05–7.21 (m, 4H, ArH); δC 12.94,
21.05, 22.29, 46.99, 47.39, 62.90, 118.23, 123.07, 127.96, 128.20,
148.51, 150.50, 157.58, 161.54 and 164.04.
17c: sticky solid (Found: C, 53.1; H, 4.7; N, 7.9. C23H25N3-
Br2O requires C, 53.2; H, 4.85; N, 8.1%); νmax (KBr)/cmϪ1 1626
and 1584; δH 0.72 (3H, t, J 7.1 Hz, OCH2CH3), 1.26 (6H, s, 2 ×
CH3), 1.35 (6H, s, 2 × CH3), 3.71 (2H, q, J 7.1 Hz, OCH2CH3),
6.56 (2H, d, J 8.6 Hz, ArH), 6.81 (2H, d, J 8.6 Hz, ArH) and
7.18 (1H, d, J 8.6 Hz, ArH).
Reaction of 3-methyl-2-(o-tolylamino)but-2-enenitrile 3d. The
reaction of 3d (947 mg, 5.30 mmol) with Cu(OAc)2ؒH2O (2.03
g, 11.2 mmol) in the presence of pyridine (876 mg, 11.2 mmol)
in EtOH (50 cm3) for 24 h gave 3,3,4,4-tetramethyl-2,5-bis(o-
tolylimino)adiponitrile 14d (324 mg, 34%) and 2-[2-cyano-1,1-
dimethyl-N-(o-tolyl)-2-(o-tolylimino)ethylamino]-3-methylbut-
2-enenitrile 15d (72 mg, 8%).
14d: mp 132–133 ЊC (from n-hexane–EtOAc) (Found: C,
77.6; H 6.8; N, 15.2. C24H26N4 requires C, 77.8; H, 7.1; N,
15.1%); νmax (KBr)/cmϪ1 2200 and 1603; δH 1.51 (12H, s, 4 ×
CH3), 2.10 (6H, s, 2 × ArCH3), 6.72–6.78 (2H, m, 2 × ArH)
and 7.02–7.18 (6H, m, 2 × ArH); δC 17.85, 23.04, 48.21, 111.15,
117.75, 125.79, 126.62, 127.06, 129.49, 130.56, 147.45 and
149.15; m/z 370 (Mϩ, 26%), 355 (Mϩ – Me, 44), 185 (100).
15d: sticky solid (Found: C, 77.6; H, 7.0; N, 15.0. C24H26N4
requires C, 77.8; H, 7.1; N, 15.1%); νmax (neat)/cmϪ1 2912
and 1622; δH 1.67 (6H, s, 2 × CH3), 1.94 (3H, s, ArCH3), 2.00
(3H, s, ArCH3), 2.03 (3H, s, CH3), 2.36 (3H, s, CH3), 6.57–6.64
(1H, m, ArH), 7.01–7.17 (6H, m, ArH) and 7.47–7.54 (1H, m,
ArH); δC 17.51, 20.42, 21.62, 23.04, 24.82, 67.34, 11.13, 114.22,
117.40, 118.76, 126.27, 126.51, 126.58, 127.07, 129.35, 129.90,
130.51, 132.04, 137.39, 143.22, 146.92, 147.19 and 154.35;
m/z 370 (Mϩ, 31%), 355 (Mϩ – CH3, 60), 185 (100).
Reaction of 2-(4-chlorophenylamino)-3-methylbut-2-enenitrile
3b. The reaction of 3b (971 mg, 4.70 mmol) with Cu(OAc)2ؒ
H2O (1.88 g, 10.34 mmol) in the presence of pyridine (818 mg,
10.34 mmol) in EtOH (50 cm3) for 60 h gave 2,5-bis(4-chloro-
phenylimino)-3,3,4,4-tetramethyladiponitrile 14b (201 mg,
21%),
2-[N-(4-chlorophenyl)-2-(4-chlorophenylimino)-2-
cyano-1,1-dimethylethylamino]-3-methylbut-2-enenitrile 15b
(331 mg, 34%), and N-(4-chlorophenyl)-4-(4-chlorophenyl-
imino)-4-cyano-2,2,3,3-tetramethylbutyrimidic acid ethyl ester
17b (237 mg, 24%).
14b: mp 187–188 ЊC (from n-hexane) (Found: C, 64.3; H,
5.0; N, 13.5. C22H20Cl2N4 requires C, 64.2; H, 4.90; N, 13.6%);
νmax (KBr)/cmϪ1 2213 and 1617; δH 1.54 (12H, s, 4 × CH3), 6.94
(4H, d, J 6.7 Hz, 2 × ArH) and 7.36 (4H, d, J 6.7 Hz, 2 × ArH);
δC 22.82, 48.31, 110.93, 121.14, 129.44, 132.82, 146.84 and
150.12.
15b: mp 74–75 ЊC (from n-hexane–CH2Cl2) (Found: C, 64.3;
H, 5.15; N, 13.7. C22H20Cl2N4 requires C, 64.2; H, 4.9; N,
13.6%; δH 1.65 (6H, s, 2 × CH3), 2.02 (3H, s, ArCH3), 2.11 (3H,
s, CH3), 6.87 (2H, d, J 7.8 Hz, ArH), 6.90 (2H, d, J 8.6 Hz,
ArH), 7.18 (2H, d, J 8.6 Hz, ArH) and 7.20 (1H, d, J 7.8 Hz,
ArH); δC 20.36, 22.23, 23.42, 65.44, 111.17, 111.63, 117.72,
121.06, 122.81, 128.78, 129.40, 129.50, 133.09, 143.22, 146.32,
149.78 and 158.78.
17b: mp 88–89 ЊC (from n-hexane–EtOAc (10:1) (Found:
C, 66.5; H, 5.9; N, 10.2. C23H25N3Cl2O requires C, 66.7; H,
6.1; N, 10.1%); νmax (KBr)/cmϪ1 1637 and 1581; δH 0.69 (3H, t,
J 7.1 Hz, OCH2CH3), 1.25 (6H, s, 2 × CH3), 1.33 (6H, s, 2 ×
CH3), 3.69 (2H, q, J 7.1 Hz, OCH2CH3), 6.55 (2H, d, J 8.6 Hz,
ArH), 6.79 (2H, d, J 8.6 Hz, ArH) and 7.20 (1H, d, J 8.6 Hz,
ArH); δC 12.94, 21.05, 22.29, 46.99, 47.39, 62.90, 118.23,
123.07, 127.96, 128.20, 148.51, 150.50, 157.58, 161.54 and
164.04.
Reaction of 3-methyl-2-(m-tolylamino)but-2-enenitrile 3e. The
reaction of 3e (998 mg, 5.36 mmol) with Cu(OAc)2ؒH2O (2.14 g,
11.8 mmol) in the presence of pyridine (933 mg, 11.8 mmol)
in EtOH (50 cm3) for 24 h gave 3,3,4,4-tetramethyl-2,5-bis(m-
tolylimino)adiponitrile 14e (371 mg, 37%) and 2-[2-cyano-1,1-
dimethyl-N-(m-tolyl)-2-(m-tolylimino)ethylamino]-3-methyl-
but-2-enenitrile 15e (310 mg, 31%).
14e: mp 62–64 ЊC (from n-hexane) (Found: C, 77.85; H 6.8;
N, 15.3. C24H26N4 requires C, 77.8; H, 7.1; N, 15.1%); νmax
(KBr)/cmϪ1 2216 and 1599; δH 1.45 (12H, s, 4 × CH3), 2.23
(6H, s, 2 × ArCH3), 6.67–6.76 (4H, m, 2 × ArH), 6.95 (2H, d, J
7.7 Hz, 2 × ArH) and 7.16 (2H, t, J 8.0 Hz, 2 × ArH); δC 21.21,
22.83, 48.01, 111.07, 116.45, 120.22, 127.64, 128.94, 138.99,
148.61 and 149.15.
15e: mp 74–75 ЊC (from n-hexane–CH2Cl2) (Found: C,
77.7; H 7.3; N, 15.25. C24H26N4 requires C, 77.8; H, 7.1; N,
15.1%); νmax (neat)/cmϪ1 2209 and 1633; δH 1.64 (6H, s, 2 ×
CH3), 2.02 (3H, s, ArCH3), 2.09 (3H, s, ArCH3), 2.23 (3H, s,
CH3), 2.28 (3H, s, CH3), 6.64–6.73 (2H, m, ArH), 6.75–6.84
(3H, m, ArH), 6.95–7.02 (1H, m, ArH), 7.04–7.12 (1H, m,
ArH) and 7.16–7.24 (1H, m, ArH); δC 20.29, 21.26, 21.67,
22.11, 23.27, 65.14, 111.41, 111.94, 116.11, 118.10, 118.79,
Reaction of 2-(4-bromophenylamino)-3-methylbut-2-enenitrile
3c. The reaction of 3c (432 mg, 1.72 mmol) with Cu(OAc)2ؒH2O
(687 mg, 3.78 mmol) in the presence of pyridine (299 mg, 3.78
mmol) for 48 h in EtOH gave 2,5-bis(4-bromophenylimino)-
3,3,4,4-tetramethyladiponitrile 14c (100 mg, 24%), 2-[N-(4-
bromophenyl)-2-(4-bromophenylimino)-2-cyano-1,1-dimethyl-
ethylamino]-3-methylbut-2-enenitrile 15c (149 mg, 35%), and
2366
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119.92, 122.27, 124.12, 127.70, 129.03, 129.08, 138.98, 139.13,
144.67, 148.37, 149.77 and 158.0.
νmax (KBr)/cmϪ1 2200 and 1621; δH 1.14–1.41 (6H, m, 3 × CH2),
1.56–1.81 (10H, m, 5 × CH2), 2.44 (4H, d, J 12.3 Hz, 2 × CH2),
6.93 (4H, d, J 7.9 Hz, 2 × ArH), 7.17 (2H, t, J 7.9 Hz, 2 × ArH)
and 7.30 (4H, t, J 7.9 Hz, 2 × ArH); δC 22.88, 25.46, 29.51,
53.47, 111.66, 119.62, 126.94, 129.18, 147.88 and 149.16.
15i: sticky solid (Found: C, 79.4; H, 7.1; N, 13.3. C28H30N4
requires C, 79.6; H, 7.2; N, 13.3%); νmax (neat)/cmϪ1 2208 and
1626; δH 1.15–1.86 (12H, m, 4 × CH3), 1.88–2.10 (2H, m, CH3),
2.39–2.53 (4H, m, CH3), 2.53–2.68 (2H, m, CH3), 6.80 (2H, d,
J 7.5 Hz, ArH) and 7.04–7.41 (8H, m, 2 × ArH); δC 23.12,
25.08, 25.79, 26.87, 27.65, 29.92, 32.13, 32.82, 66.83, 109.70,
111.19, 118.85, 119.20, 119.52, 125.84, 126.84, 127.87, 129.03,
129.09, 144.79, 146.14, 148.54 and 163.74.
Reaction of 3-methyl-2-(p-tolylamino)but-2-enenitrile 3f. The
reaction of 3f (998 mg, 5.30 mmol) with Cu(OAc)2ؒH2O (2.12 g,
11.7 mmol) in the presence of pyridine (922 mg, 11.7 mmol) in
EtOH (50 cm3) for 22 h gave 3,3,4,4-tetramethyl-2,5-bis(p-
tolylimino)adiponitrile 14f (360 mg, 37%), 2-[2-cyano-1,1-
dimethyl-N-(p-tolyl)-2-(p-tolylimino)ethylamino]-3-methylbut-
2-enenitrile 15f (325 mg, 33%).
14f: mp 116–117 ЊC (from n-hexane) (Found: C, 78.0; H,
7.15; N, 15.0. C24H26N4 requires C, 77.8; H, 7.1; N, 15.1%); νmax
(KBr)/cmϪ1 2208 and 1604; δH 1.42 (12H, s, 4 × CH3), 2.21 (6H,
s, 2 × ArCH3), 6.84 (4H, d, J 7.8 Hz, 2 × ArH) and 7.06 (4H, d,
J 7.8 Hz, 2 × ArH); δC 20.92, 22.73, 47.97, 111.27, 119.75,
129.61, 136.89, 146.00 and 148.51.
15f: mp 74–75 ЊC (from n-hexane–CH2Cl2) (Found: C, 77.7;
H 7.3; N, 15.25. C24H26N4 requires C, 77.8; H, 7.1; N, 15.1%);
νmax (neat)/cmϪ1 2209 and 1633; δH 1.64 (6H, s, 2 × CH3), 2.02
(3H, s, ArCH3), 2.09 (3H, s, ArCH3), 2.23 (3H, s, CH3), 2.28
(3H, s, CH3), 6.64–6.73 (2H, m, ArH), 6.75–6.84 (3H, m, ArH),
6.95–7.02 (1H, m, ArH), 7.04–7.12 (1H, m, ArH) and 7.16–7.24
(1H, m, ArH); δC 20.29, 21.26, 21.67, 22.11, 23.27, 65.14,
111.41, 111.94, 116.11, 118.10, 118.79, 119.92, 122.27, 124.12,
127.70, 129.03, 129.08, 138.98, 139.13, 144.67, 148.37, 149.77
and 158.0.
Reaction of 3-ethyl-2-phenylaminopent-2-enenitrile 3j. The
reaction of 3j (1.06 g, 5.24 mmol) with Cu(OAc)2ؒH2O (2.09 g,
11.5 mmol) in the presence of pyridine (912 mg, 11.5 mmol) in
EtOH (52 cm3) for 48 h gave 2-{1-[cyano(phenylimino)methyl]-
1-ethyl-N-phenylpropylamino}-3-ethylpent-2-enenitrile
15j
(434 mg, 41%); sticky solid (Found: C, 78.5; H, 7.5; N, 14.0.
C26H30N4 requires C, 78.35; H, 7.6; N, 14.1%); νmax (neat)/cmϪ1
2209 and 1633; δH 0.67 (3H, t, J 7.5 Hz, CH3), 0.98 (6H, t, J 7.5
Hz, 2 × CH3), 1.11 (3H, t, J 7.5 Hz, CH3), 2.10 (2H, sextet,
J 7.3Hz, CH2), 2.29–2.52 (6H, m, 3 × CH2), 6.95–7.12 (3H, m,
ArH), 7.13–7.34 (5H, m, ArH) and 7.36–7.51 (2H, m, ArH);
δC 8.27, 10.36, 12.39, 23.83, 24.86, 25.93, 70.09, 111.56, 113.13,
119.40, 119.58, 123.88, 124.39, 127.07, 128.92, 129.34, 146.62,
Reaction
of
2-(4-methoxyphenylamino)-3-methylbut-2-
148.60, 149.29 and 166.39; m/z 398 (Mϩ, 14%), 369 (Mϩ
–
enenitrile 3g. The reaction of 3g (889 mg, 4.40 mmol) with
Cu(OAc)2ؒH2O (1.60 g, 8.80 mmol) in the presence of pyridine
(696 mg, 8.80 mmol) in EtOH (44 cm3) for 12 h gave 2,5-bis-
(4-methoxyphenylimino)-3,3,4,4-tetramethyladiponitrile 14g
(127 mg, 15%); mp 140–142 ЊC (from n-hexane) (Found: C,
71.4; H 6.4; N, 13.8. C24H26N4O2 requires C, 71.6; H, 6.5; N,
13.9%); νmax (KBr)/cmϪ1 2206 and 1608; δH 1.45 (12H, s, 4 ×
CH3), 3.73 (6H, s, 2 × CH3O), 6.83 (4H, d, J 8.9 Hz, 2 × ArH)
and 7.02 (4H, d, J 8.9 Hz, 2 × ArH); δC 22.83, 48.20, 55.40,
111.80, 114.26, 122.15, 141.32, 146.95 and 158.98.
CH2CH3, 14), 342 (29), 306 (15), 269 (100). m/z HRMS (EI)
Calc. for C26H30N4: [M ϩ H]; 398.2470. Found: m/z, 398.2472.
Reaction of 15a with AlCl3
To a solution of 15a (89 mg, 0.26 mmol) in benzene (3 cm3) was
added anhydrous AlCl3 (69 mg, 0.52 mmol). The mixture was
stirred for 48 h at rt. Water (30 cm3) was added into the mixture
and then the mixture was extracted with CH2Cl2 (30 cm3 × 2).
The combined extract was dried (MgSO4). Removal of the
solvent, followed by chromatography (2 × 20 cm) of the residue
using a mixture of n-hexane and EtOAc (5:1) gave 2-(2,3-
dihydro-2,2-dimethyl-3-phenylimino-1H-indol-1-yl)-3-methyl-
but-2-enenitrile 18 (29 mg, 35%) and 11a (7 mg, 12%).
18: sticky solid (Found: C, 81.0; H, 6.9; N, 13.1. C21H21N3
requires C, 80.0; H, 6.7; N, 13.3%); νmax (neat)/cmϪ1 2209, 1660
and 1598; δH 1.39 (3H, s, CH3), 1.56 (3H, s, CH3), 1.87 (3H, s,
CH3), 2.22 (3H, s, CH3), 6.56 (1H, t, J 8.2 Hz, ArH), 6.82 (1H,
d, J 7.6 Hz, ArH), 7.44 (1H, t, J 8.2 Hz, 3 × ArH), 7.61 (1H, d,
J 7.6 Hz, ArH); m/z 315 (Mϩ, 36%), 300 (29), 235 (100).
Reaction of (E )- and (Z )-3-methyl-2-(p-tolylamino)pent-2-
enenitrile (E )- and (Z )-3h. The reaction of a mixture of (E)-
and (Z)-3h (757 mg, 3.78 mmol) with Cu(OAc)2ؒH2O (1.51 g,
8.32 mmol) in the presence of pyridine (658 mg, 8.32 mmol)
in EtOH (38 cm3) for 22 h gave a diastereomeric mixture of
3,4-diethyl-3,4-dimethyl-2,5-bis(p-tolylimino)adiponitrile 14h
(191 mg, 25%) and a diastereomeric mixture of 2-{1-[cyano-
(p-tolylimino)methyl]-1-methyl-N-(p-tolyl)propylamino}-3-
methylpent-2-enenitrile 15h (132 mg, 17%).
14h: sticky solid; δH 0.80–0.92 (6H, m, 2 × CH3), 1.36–1.44
(6H, m, 2 × CH3), 1.63–1.87 (2H, m, CH2), 2.27 (6H, s, 2 ×
ArCH3), 2.24–2.42 (2H, m, CH2), 6.81–6.92 (4H, m, 2 × ArH),
7.05–7.16 (4H, m, 2 × ArH).
15h: sticky solid; δH 0.80–0.91 (4.5H, m, CH3), 1.05 (1.5H, t,
J 7.5 Hz, CH3), 1.57–1.63 (3H, m, CH3), 1.97–2.03 (3H, m,
CH3), 2.04 (2H, q, J 7.5 Hz, CH2), 2.22 (3H, s, ArCH3), 2.29
(3H, s, ArCH3), 2.39 (1H, qd, J 7.6, 2.0 Hz, CH2), 2.56 (1H, d,
J 7.6 Hz, CH2), 6.77–6.83 (2H, m, ArH), 6.94–7.10 (4H, m,
ArH) and 7.10–7.16 (2H, m, ArH); m/z 398 (Mϩ, 10%), 369
(Mϩ – CH2CH3, 5), 342 (9), 292 (11), 255 (100). m/z HRMS (EI)
Calc. for C26H30N4: [M ϩ H]; 398.2470. Found: m/z, 398.2472.
General procedure for the synthesis of 1,2-dihydroindol-3-ones 11
A mixture of compound 15 and Cu(OAc)2ؒH2O in HOAc
(3 cm3) was heated for an appropriate length of time at reflux.
The reaction mixture was cooled to rt, followed by addition of
water (50 cm3), and CH2Cl2 (30 cm3), and then neutralized with
aqueous Na2CO3. The mixture was extracted with CH2Cl2
(30 cm3 × 2). The combined extract was dried (MgSO4).
Evaporation of the solvent gave a brown liquid, which was
chromatographed on a silica gel column (2 × 20 cm3) using a
mixture of n-hexane and EtOAc (5:1) as the eluent.
2-(2,3-Dihydro-2,2-dimethyl-3-oxo-1H-indol-1-yl)-3-methyl-
but-2-enenitrile 11a. The reaction of 15a (164 mg, 0.48 mmol)
with Cu(OAc)2ؒH2O (96 mg, 0.53 mmol) in HOAc (10 cm3) for
14 h gave 11a (86 mg, 75%). From the reaction of 15a (273 mg,
0.80 mmol) in HOAc (20 cm3) for 30 h was obtained 11a
(108 mg, 56%).
Reaction of 1,1Ј-cyclohexylidene-1-phenylaminoacetonitrile
3i. The reaction of 3i (998 mg, 4.70 mmol) with Cu(OAc)2ؒH2O
(1.88 g, 10.3 mmol) in the presence of pyridine (818 mg,
10.3 mmol) in EtOH (50 cm3) for 48 h gave {1Ј-[cyano(phenyl-
imino)methyl]bicyclohexan-1-yl}phenyliminoacetonitrile 14i
(198 mg, 20%) and {1-[cyano(phenylimino)methyl]-N-phenyl-
cyclohexylamino}cyclohexylidenacetonitrile 15i (312 mg, 31%).
14i: mp 224–225 ЊC (from n-hexane–EtOAc) (Found: C, 79.7;
H 7.2; N, 13.3. C28H30N4 requires C, 79.6; H, 7.2; N, 13.3%);
2-(5-Chloro-2,3-dihydro-2,2-dimethyl-3-oxo-1H-indol-1-yl)-3-
methylbut-2-enenitrile 11b. The reaction of 15b (149 mg, 0.36
mmol) with Cu(OAc)2ؒH2O (78 mg, 0.43 mmol) in HOAc
J. Chem. Soc., Perkin Trans. 1, 2002, 2360–2369
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(8 cm3) for 96 h gave 11b (85 mg, 86%): mp 91–92 ЊC (from n-
hexane–CH2Cl2) (Found: C, 65.4; H 5.6; N, 10.1. C15H15ClN2O
requires C, 65.6; H, 5.6; N, 10.1%); νmax (neat)/cmϪ1 2960, 2209,
1717 and 1607; δH 1.22 (3H, s, CH3), 1.39 (3H, s, CH3), 1.81
(3H, s, CH3), 2.22 (3H, s, CH3), 6.53 (1H, dd, J 8.7, 2.2 Hz,
ArH), 7.39 (1H, d, J 8.7 Hz, ArH) and 7.57 (1H, d, J 2.2 Hz,
ArH); δC 20.49, 22.01, 22.45, 22.53, 70.59, 105.49, 111.45,
116.10, 120.37, 124.52, 125.00, 137.38, 155.14, 160.38 and
201.41; m/z 276 (Mϩ ϩ 2, 29%), 274 (Mϩ, 89), 259 (44), 231
(100), 152 (51).
d, J 8.3 Hz, ArH) and 7.39 (1H, s, ArH); δC 13.99, 20.29, 21.32,
22.07, 22.32, 69.96, 106.02, 110.11, 116.34, 119.25, 124.45,
129.11, 138.76, 155.16, 159.55 and 202.57; m/z 254 (Mϩ, 100%),
239 (57), 211 (98), 132 (43).
2-(2,3-Dihydro-2,5-dimethyl-2-ethyl-3-oxo-1H-indol-1-yl)-3-
methylpent-2-enenitrile 11h. The reaction of 15h (81 mg,
0.20 mmol) with Cu(OAc)2ؒH2O (44 mg, 0.24 mmol) in HOAc
(1 cm3) for 480 h gave 11h (35 mg, 60%); sticky solid; νmax (neat)/
cmϪ1 2968, 2208, 1692 and 1606; δH 0.77–0.83 (3H, m), 1.02
(2H, m), 1.23–1.44 (4H, m), 1.45 (2H, m), 1.75 (1H, m), 1.97
(1H, m), 2.27–2.34 (5H, m), 2.61 (1H, m), 6.47–6.64 (1H, m,
ArH), 7.31–7.39 (1H, m, ArH) and 7.47 (1H, m, ArH); m/z of
2-(5-Bromo-2,3-dihydro-2,2-dimethyl-3-oxo-1H-indol-1-yl)-3-
methylbut-2-enenitrile 11c. The reaction of 15c (85 mg,
0.17 mmol) with Cu(OAc)2ؒH2O (36 mg, 0.20 mmol) in HOAc
(4 cm3) for 28 h gave 15c (30 mg, 35%) and 11c (15 mg, 45%);
sticky solid (Found: C, 56.6; H, 4.9; N, 9.0. C15H15BrN2O
requires C, 56.4; H, 4.7; N, 8.8%); νmax (neat)/cmϪ1 2990, 2208
and 1698; δH 1.29 (3H, s, CH3), 1.47 (3H, s, CH3), 1.88 (3H, s,
CH3), 2.29 (3H, s, CH3), 6.55 (1H, d, J 8.7 Hz, ArH), 7.60 (1H,
dd, J 8.7, 2.1 Hz, ArH) and 7.81 (1H, d, J 2.1 Hz, ArH);
δC 20.55, 22.01, 22.51, 22.61, 70.49, 105.41, 111.85, 111.92,
116.12, 120.93, 127.72, 140.03, 155.45, 160.46 and 201.27; m/z
320 (Mϩ ϩ 2, 97%), 318 (Mϩ, 100), 305 (Mϩ ϩ 2 – CH3, 44), 303
(Mϩ – CH3, 45), 277 (81), 275 (83).
isomer-1 282 (Mϩ, 50%), 267 (Mϩ – CH3, 10), 253 (Mϩ
–
CH2CH3, 100); m/z of isomer-2 282 (Mϩ, 53%), 267 (Mϩ – CH3,
10), 253 (Mϩ – CH2CH3, 100). m/z HRMS (EI) Calc. for
C18H22N2O: [M ϩ H]; 282.1732. Found: m/z, 282.1743.
2-(2,2-Diethyl-2,3-dihydro-3-oxo-1H-indol-1-yl)-3-ethylpent-
2-enenitrile 11j. The reaction of 15j (133 mg, 0.33 mmol) with
Cu(OAc)2ؒH2O (77 mg, 0.40 mmol) in HOAc (4 cm3) for 480 h
gave 11j (15 mg, 15%): sticky solid (Found: C, 77.2; H 8.3; N,
9.6. C19H24N2O requires C, 77.0; H, 8.2; N, 9.45%); νmax (neat)/
cmϪ1 2968, 2200, 1698 and 1606; δH 0.71 (3H, t, J 7.4 Hz, CH3),
0.78 (3H, t, J 7.4 Hz, CH3), 0.96 (3H, t, J 7.5 Hz, CH3), 1.20
(3H, t, J 7.5 Hz, CH3), 1.56 (1H, q, J 7.5 Hz, CH2), 1.71 (1H, q,
J 7.5 Hz, CH2), 1.89 (1H, q, J 7.5 Hz, CH2), 2.01 (1H, q, J 7.5
Hz, CH2), 2.16 (2H, q, J 7.5 Hz, CH2), 2.58 (2H, octet, J 7.5 Hz,
CH2), 6.49 (1H, d, J 8.3 Hz, ArH), 6.79 (1H, t, J 7.5 Hz, ArH),
7.42 (1H, t, J 8.3 Hz, ArH), 7.58 (1H, d, J 7.9 Hz, ArH);
m/z 296 (Mϩ, 22%), 267 (100).
2-(2,3-Dihydro-3-oxo-2,2,7-trimethyl-1H-indol-1-yl)-3-methyl-
but-2-enenitrile 11d. The reaction of 15d (70 mg, 0.19 mmol)
with Cu(OAc)2ؒH2O (42 mg, 0.23 mmol) in HOAc (2 cm3) for
18 h gave 11d (32 mg, 68%): sticky solid; νmax (neat)/cmϪ1 2208,
1698 and 1613; δH 1.20 (3H, s, CH3), 1.37 (3H, s, CH3), 1.86
(3H, s, CH3), 2.16 (3H, s, CH3), 2.17 (3H, s, CH3), 6.79 (1H, t,
J 7.5 Hz, ArH), 7.24 (1H, d, J 7.2 Hz, ArH) and 7.61 (1H, d,
J 7.5 Hz, ArH); δC 18.21, 20.77, 22.22, 22.62, 22.74, 70.15,
109.65, 117.04, 120.47, 120.89, 122.45, 123.00, 140.77, 155.94,
157.18 and 203.35; m/z 254 (Mϩ, 98%), 239 (73), 211 (100), 198
(21). m/z HRMS (EI) Calc. for C16H18N2O: [M ϩ H]; 254.1419.
Found: m/z, 254.1407.
Acknowledgements
The authors are grateful to the Brain Korea 21 program for
financial support of this work.
References
2-(2,3-Dihydro-3-oxo-2,2,4-trimethyl-1H-indol-1-yl)-3-
methylbut-2-enenitrile 11e(I) and 2-(2,3-dihydro-3-oxo-2,2,6-
trimethyl-1H-indol-1-yl)-3-methylbut-2-enenitrile 11e(II). The
reaction of 15e (254 mg, 0.69 mmol) with Cu(OAc)2ؒH2O
(151 mg, 0.83 mmol) in HOAc (14 cm3) for 6 h gave 11e(I)
(26 mg, 14%): mp 84–86 ЊC (from n-hexane–CH2Cl2) (Found:
C, 75.7; H 7.0; N, 11.0. C16H18N2O requires C, 75.6; H, 7.1; N,
11.0%); νmax (neat)/cmϪ1 2209, 1699 and 1598; δH 1.19 (3H, s,
CH3), 1.38 (3H, s, CH3), 1.80 (3H, s, CH3), 2.20 (3H, s, CH3),
2.53 (3H, s, CH3), 6.36 (1H, d, J 8.1 Hz, ArH), 6.58 (1H, d, J 7.4
Hz, ArH) and 7.29 (1H, t, J 7.8 Hz, ArH); δC 18.31, 20.48,
22.29, 22.47, 22.68, 69.54, 106.13, 107.40, 116.49, 117.33,
121.27, 136.78, 140.82, 157.35, 159.69 and 203.32; m/z 254 (Mϩ,
98%), 239 (100), 211 (84), 132 (25); and 11e(II) mp 81–82 ЊC
(from n-hexane–CH2Cl2) (Found: C, 75.3; H 7.35; N, 11.1.
C16H18N2O requires C, 75.6; H, 7.1; N, 11.0%); νmax (neat)/cmϪ1
2208, 1704 and 1613; δH 1.19 (3H, s, CH3), 1.37 (3H, s, CH3),
1.81 (3H, s, CH3), 2.21 (3H, s, CH3), 2.30 (3H, s, CH3), 6.35
(1H, s, ArH), 6.65 (1H, d, J 7.9 Hz, ArH) and 7.49 (1H, d, J 7.9
Hz, ArH); δC 20.35, 22.03, 22.41 (3 overlapped peaks), 69.99,
105.75, 110.15, 116.34, 116.97, 121.29, 124.79, 149.32, 157.20,
159.99 and 201.86; m/z 254 (Mϩ, 100%), 239 (75), 211 (84), 174
(20), 132 (30).
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2-(2,3-Dihydro-3-oxo-2,2,5-trimethyl-1H-indol-1-yl)-3-methyl-
but-2-enenitrile 11f. The reaction of 15f (142 mg, 0.38 mmol)
with Cu(OAc)2ؒH2O (84 mg, 0.46 mmol) in HOAc (8 cm3) for 4
h gave 11f (90 mg, 92%): mp 96–97 ЊC (from n-hexane–CH2Cl2)
(Found: C, 75.6; H 7.4; N, 11.1. C16H18N2O requires C, 75.6; H,
7.1; N, 11.0%); νmax (neat)/cmϪ1 2200, 1698 and 1613; δH 1.19
(3H, s, CH3), 1.36 (3H, s, CH3), 1.80 (3H, s, CH3), 2.19 (3H, s,
CH3), 2.23 (3H, s, CH3), 6.49 (1H, d, J 8.3 Hz, ArH), 7.27 (1H,
7 A. L. J. Beckwith and A. A. Zavitsas, J. Am. Chem. Soc., 1986, 108,
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2368
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1053.
10 The reaction of aniline (510 mg, 5.47 mmol) with Cu(OAc)2ؒH2O
(450 mg, 2.49 mmol) in HOAc (10 cm3) for 24 h at reflux under an
N2 atmosphere gave acetanilide (562 mg, 76%).
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11 Cu(OAc)2ؒH2O (450 mg) was treated with HOAc (10 cm3) at rt
and reflux temperatures for 24 h, respectively, followed by filtration
of the undissolved copper acetate. From the filtrate were obtained
280 mg (62%) and 367 mg (82%) of copper acetate, respectively.
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