New aromatic rearrangement accompanying ring closure of 2-arylpropylidenemalonodinitriles to 1-aminonaphthalene-2-carbonitriles

Article abstract of DOI:10.1016/S0040-4039(01)00938-8

Cyclization and a rearrangement in concentrated sulfuric acid of 2-(4-substituted-phenyl)propylidenemalonodinitriles (1) into 1-amino-4-methyl-6-substituted-naphthalene-2-carbonitriles (5) appears to involve a series of steps such as ipso electrophilic attack of the protonated nitrile function on the para position of the phenyl group, opening of a spirobenzenium cation or its transformation, and ring reclosure to the naphthalene framework with participation of the secondary alkyl carbocation as an active electrophile.

Full text of DOI:10.1016/S0040-4039(01)00938-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5287–5289
New aromatic rearrangement accompanying ring closure of
2-arylpropylidenemalonodinitriles to
1-aminonaphthalene-2-carbonitriles
Janusz J. Sepiol* and Jaroslaw Wilamowski
Department of Organic Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krako´w, Poland
Received 18 January 2001; revised 24 May 2001; accepted 31 May 2001
Abstract—Cyclization and a rearrangement in concentrated sulfuric acid of 2-(4-substituted-phenyl)propylidenemalonodinitriles
(1) into 1-amino-4-methyl-6-substituted-naphthalene-2-carbonitriles (5) appears to involve a series of steps such as ipso elec-
trophilic attack of the protonated nitrile function on the para position of the phenyl group, opening of a spirobenzenium cation
or its transformation, and ring reclosure to the naphthalene framework with participation of the secondary alkyl carbocation as
an active electrophile. © 2001 Elsevier Science Ltd. All rights reserved.
priate distance along the alkyl chain, from the nitrile
functions.1,2 The starting alkylidenemalonodinitriles are
mostly obtained from phenyl-substituted aldehydes or
ketones.3 This route to naphthalene aminonitriles has
attracted our attention as it could allow the introduc-
tion of another alkyl group in the second ring of
naphthalene, beside an alkyl group being present at the
‘4’ position of the above mentioned aminonitrile. Thus,
we hoped that by employing the approach outlined
here, the number of naphthalene aminonitriles available
for screening of their antifungal activity will be consid-
erably increased.
Our preliminary investigations revealed that derivatives
of 1-aminonaphthalene-2-carbonitrile having short
alkyl groups on either or both rings of the naphthalene
system are potent fungicides against such phytopatho-
genic fungi as Fusarium culmorum, Alternaria brassici-
cola, Botrytis cinerea, and Penicillium expansum. The
fungicidal activity of these compounds is comparable or
higher than the activity of some commercial fungicides.
The aminonitriles needed for these investigations are
conveniently synthesized through cyclization, in strong
acids, of a variety of alkylidenemalonodinitriles which
have phenyl or substituted-phenyl groups at the appro-
CN
NH2
2a
H2SO4
0 oC
NOE
CN
NH
H
CH3
NC
1a
CN
5
4
H
H3C
3
1,2-shift
+H
6
7
CN
2
-H
CN
1
NH
3a
8
H
NH2
4a
5a
(80 %)
NOE
Scheme 1. Cyclization and rearrangement of 2-(4-methylphenyl)propylidenemalonodinitrile (1a) to 1-amino-4,6-dimethylnaph-
thalene-2-carbonitrile (5a).
Keywords: arylalkylidenemalonodinitriles; cyclization; rearrangement; aminonitriles.
* Corresponding author. Fax (+04812)6340515; e-mail: sepiol@chemia.uj.edu.pl
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00938-8

5288
J. J. Sepiol, J. Wilamowski / Tetrahedron Letters 42 (2001) 5287–5289
Dissolving 1a in ice-cold concentrated sulfuric acid for
2 h followed by quenching the solution with ice
afforded an aminonitrile with mp 146–147°C in 80%
yield. Initially we presumed that the cyclization of 1a
occurred in a straightforward manner, with ring closure
in the meta position with respect to the methyl group of
After unequivocal establishment of the structure of 5a,
it became apparent that during cyclization of 1a a
rearrangement of the whole carbocyclic system had
taken place. We rejected the possibility of a migration
of the methyl group which was initially present in the
benzene system of 1a. Such a migration of the methyl
group to the neighboring position, accompanying the
straightforward cyclization to 2a, appears less feasible
due to the low nucleophilicity of 2a or potential inter-
mediate products related to 2a. We present in Scheme 1
a hypothetical mechanism describing the cyclization of
1a to 5a and a rearrangement of the carbon framework
of 1a. We assume that the methyl function of the
p-tolyl group of 1a activates its para position and
allows ipso electrophilic attack on that position which
leads to the spirobenzenium cation 3a. In the next step
3a might undergo a 1,2-alkyl shift which gives 4a. There
is also a possibility of ring opening of 3a with an
involvement of the secondary carbocation as an active
electrophile. The presence of such a carbocation could
have an influence on a rearrangement of 1a into 5a in
relatively high yield.
1
the benzene ring, and gave 2a. However, the H NMR
spectra and NOE experiments showed that the cycliza-
tion product had the structure 5a, being a derivative of
1,7-dimethylnaphthalene (Scheme 1).
It became apparent that during cyclization either a
migration of the methyl group in 1a occurred or a
rearrangement of the whole carbocyclic system had
taken place. The structure of 5a was further supported
by its conversion to 4,6-dimethylnaphthalene-1-amine
through the removal of the nitrile group from 5a, and
finally by the deamination of this amine to 1,7-
dimethylnaphthalene. Aminonitrile 5a (300 mg, 1.53
mmol) and sodium hydroxide (0.76 g, 19 mmol) were
dissolved in ethanol (100 ml). The solution was heated
in a 300 ml autoclave at 240°C (ꢀ3.5 MPa) for 4 h.
The mixture was diluted with water (50 ml) and ethanol
was removed. A dark oil which separated from the
solution was extracted with toluene. Dry hydrogen
chloride was passed through the toluene solution to
afford 268 mg (85%) of 4,6-dimethylnaphthalene-1-
amine hydrochloride. The hydrochloride was converted
into the semisolid free amine which, after sublimation
under reduced pressure and recrystallization from n-
hexane, gave 219 mg (81%) of colorless needles with mp
71.5°C.
In contrast to the results presented in Scheme 1, an
attempt to cyclize 2-methyl-3-(2-methylphenyl)prop-1-
en-1,1-dicarbonitrile, an isomer of 1a, to 1-amino-3,5-
dimethylnaphthalene-2-carbonitrile, failed to give any
isolable product. Although a magenta coloration of the
solution of this dinitrile in sulfuric acid might indicate
the presence of a spirobenzenium cation similar to 3a,
the ring opening of the cation appears to give a very
reactive and unstable primary carbocation which pre-
sumably undergoes side reactions competing with the
cyclization. Successful rearrangement of other dinitriles
1 into 5 in moderate to high yields might thus depend
on the presence of more stable electrophiles in the
intermediate stages of the cyclization. In order to inves-
tigate the scope of the rearrangement and to evaluate
the influence of substituents on the benzene ring of 1 on
the outcome of the reaction, several dinitriles 1 were
4,6-Dimethylnaphthalene-1-ammonium chloride was
diazotized at 0°C and treated with 30% hypophospho-
rous acid. The usual work-up of the reaction mixture
afforded 1,7-dimethylnaphthalene in 51% yield. Its
spectroscopic properties were identical with those of an
authentic sample of the hydrocarbon.
COCH3
X
i, ii, iii
CHO
v
iv
CN
+
X
NH
CN
X
X
X
NC
CN
5
6
NH2
1
3
7
X = CH3, C2H5, Cl, F, OCH3
Scheme 2. Synthesis of 1-amino-4-methyl-6-substituted-naphthalene-2-carbonitriles 5 from acetophenones 6. Reagents and condi-
tions: (i) ClCH2COOC2H5, NaH/CH3CN; (ii) NaOH/C2H5OH; (iii) HCl/H2O; (iv) CH2(CN)2, CH3COOH, CH3COONH4/C6H6;
(v) H2SO4, 0°C.
Table 1. Preparation of aldehydes 7, dinitriles 1 and aminonitriles 5
1, 5, 7
X
Yield of 7 (%)
Yield of 1 (%)
Yield of 5 (%)
Mp of 5 (°C)
a
b
c
d
e
CH3
C2H5
Cl
63
45
58
65
40
80
71
77
69
68
80
61
92
25
66
146–147
105–106
180–180.5
152–153
166–167.5
F
OCH3

J. J. Sepiol, J. Wilamowski / Tetrahedron Letters 42 (2001) 5287–5289
5289
prepared. The dinitriles were synthesized from ace-
tophenones 6 essentially following the reported proce-
dures for the preparation of aldehydes 7 and the
condensation of 7 with malonodinitrile (Scheme 2,
Table 1).3,4
Scientific Research of Poland (Grant No. 3 T09B 030
14) is gratefully acknowledged.
References
The dinitriles were cyclized in the following manner: 1
(3.0 mmol) was slowly added dropwise while stirring
into ice-cold concentrated sulfuric acid (5 ml). The
solution turned yellow, orange and finally dark red.
After 2 h at 0°C, the solution was poured onto ice to
give a pale yellow precipitate. After the usual work-up,
the product was chromatographed on silica gel and
sublimed under reduced pressure.5
1. Taylor, E. C.; McKillop, A. In The Advances in Organic
Chemistry; Taylor, E. C., Ed. The chemistry of cyclic
enaminonitriles and o-aminonitriles. Interscience: New
York, 1970; Vol. 5, pp. 79–308.
2. Bamfield, P.; Gordon, P. F. Chem. Soc. Rev. 1984, 13,
441–488.
3. Campaigne, E.; Maulding, D. R.; Roelofs, W. L. J. Org.
Chem. 1964, 29, 1543–1549.
4. Pergola, R. D.; di Battista, P. Synth. Commun. 1984, 14,
121–126.
The presence of the first order substituents in 1 at the
para position with the respect to the site of the elec-
trophilic attack, resulted in a relatively high yield of the
rearranged aminonitriles 5. However, fluorine-substi-
tuted 1d gave 5d in a disappointingly low yield while
chlorine-substituted 1c afforded 5c in nearly quantita-
tive yield. Since the methoxy group does not migrate
during aromatic rearrangements, cyclization of 1d to 5d
furnished additional support to the mechanism pre-
sented in Scheme 1. As in the case of 5a, the structure
of the other aminonitriles 5 was established through
NOE experiments.
5. All new compounds 1a–e and 5a–e gave satisfactory ana-
lytical and spectroscopic data. Selected spectra and physi-
cal data: Compound 1a (yellowish oil, bp 126–128°C/3
1
hPa): H NMR (CDCl3): l 7.29 (d, J=10.9 Hz, 1H), 7.19
(d, J=7.8 Hz, 2H), 7.13 (d, J=7.9 Hz, 2H), 4.06–4.13 (m,
1H), 1.53 (d, J=6.9 Hz, 3H), 2.35 (s, 3H); 13C NMR
(CDCl3): l 171.7, 138.1, 136.2, 130.1 (2C), 126.8 (2C),
112.0, 110.6, 42.5, 87.5, 21.0, 19.5. Anal. calcd for
C13H12N2: C, 79.56; H, 6.16; N, 14.27. Found: C, 79.44;
H, 6.21; N, 14.14%. Compound 5a (pale yellow needles
1
from methanol, mp 146–147°C): H NMR (CDCl3): l 2.48
The results presented here involve a study on the
cyclization of dinitriles 1 having symmetrical, para-sub-
stituted phenyl groups. However, an investigation of
the rearrangement of arylalkylidenemalonodinitriles
which have unsymmetrical or unsymmetrically substi-
tuted aryl groups seems to promise interesting results.
By employing the synthetic approach presented here,
new routes to some polycyclic aromatic systems might
be designed.
(s, 3H), 2.54 (s, 3H), 4.91 (br. s, 2H), 7.09 (s, 1H), 7.36
(dd, 1H, J=8.5, 1.5 Hz), 7.67 (d, 1H, J=1.5 Hz), 7.71 (d,
1H, J=8.5 Hz); 13C NMR (CDCl3): l 18.7, 21.9, 88.5,
118.9, 120.4, 121.6, 124.0, 124.5, 125.8, 127.9, 135.3, 138.9,
147.0. Anal. calcd for C13H12N2: C, 79.56; H, 6.16; N,
14.27. Found: C, 79.40; H, 6.11; N, 14.22%. 4,6-Dimethyl-
naphthalene-1-amine (colorless needles from n-hexane, mp
71.5°C): 1H NMR (CDCl3): l 7.71 (dd, J=8.6, 1.6 Hz,
1H), 7.70 (d, J=1.6 Hz, 1H), 7.28 (d, J=8.6 Hz, 1H), 7.06
(d, J=7.3 Hz, 1H), 6.59 (d, J=7.3 Hz, 1H), 3.93 (br. s,
2H), 2.55 (s, 3H), 2.52 (s, 3H); 13C NMR (CDCl3): l
140.4, 135.1, 133.4, 126.8, 126.6, 124.2, 124.0, 122.3, 121.1,
108.8, 21.9, 18.9. Anal. calcd for C12H13N: C, 84.17; H,
7.65; N, 8.18. Found: C, 83.99; H, 7.64; N, 8.22%.
Acknowledgements
Support of this research by the State Committee for
.