Synthesis of α-arylnaphthalenes from diphenylacetaldehydes and 1,1-diphenylacetones

Article abstract of DOI:10.1016/j.tet.2008.04.067

Condensation of diphenylacetaldehydes and 1,1-diphenylacetones with malonodinitrile and cyclization of obtained aryl-ylidenemalonodinitriles in concentrated sulfuric acid leads to 1-amino-4-arylnaphthalene-2-carbonitriles. The benzannulation reaction is a

Full text of DOI:10.1016/j.tet.2008.04.067

Tetrahedron 64 (2008) 6452–6460
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of
a
-arylnaphthalenes from diphenylacetaldehydes and
1,1-diphenylacetones
*
´
Bart1omiej Kozik , Jaros1aw Wilamowski, Maciej Gora, Janusz J. Sepio1
Department of Organic Chemistry, Jagiellonian University, Ingardena 3, PL-30-060 Krako´w, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Condensation of diphenylacetaldehydes and 1,1-diphenylacetones with malonodinitrile and cyclization
of obtained aryl-ylidenemalonodinitriles in concentrated sulfuric acid leads to 1-amino-4-arylnaph-
thalene-2-carbonitriles. The benzannulation reaction is accompanied by a quasi-aromatic rearrangement.
Preliminary tests of some synthesized aminonitriles have revealed their considerable biological activity
against phytopathogenic fungi.
Received 23 January 2008
Received in revised form 7 April 2008
Accepted 17 April 2008
Available online 22 April 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
1-Arylnaphthalenes
Aromatic aminonitriles
Rearrangement
Cyclization
Fungistatic activity
1. Introduction
was previously applied in syntheses of other aromatic, vicinal
aminonitriles, derivatives of alkylated naphthalene11 or phenan-
Biaryls continue to attract considerable attention. Special in-
terest is focused on 2,20-disubstituted-1,10-binaphthyls and their
analogues. This is, particularly, due to the presence of a stereogenic
axis and the ability of these compounds to form atropoisomers.1,2
The same properties are exhibited by substituted 1,10-biphenyls. A
third group of compounds possessing a stereogenic axis contains 1-
(substituted-phenyl)naphthalenes. These three major groups of
biaryls appear to have enormous and steadily increasing applica-
tions in chemistry and related areas. First of all, chiral biaryls find
important applications as catalysts in the synthesis of chiral prod-
ucts possessing high or very high enantiopurity.3–5 Hence, there are
many recent reports and reviews on biaryl synthesis with control of
axial chirality.4–6 Furthermore, chiral biaryls are employed as
building units in a variety of natural products and biologically ac-
tive compounds.5,7 They have also many other applications, for
example, in synthesis of conducting polymers8 or liquid crystals.9
In a recent communication we reported a synthesis of de-
threne12 and cycloalkaphenanthrene.13 In this report we wish to
present all details of our approach leading to 4-phenyl- or 4-
(substituted-phenyl)-1-aminonaphthalene-2-carbonitriles. Results
of the biological tests encourage us to extend the research to the
chloro-substituted aminonitriles.
2. Results and discussion
An example of this synthetic strategy is shown in Scheme 1.
Starting ketone
1 was condensed with malonodinitrile and
afforded the dinitrile 2. Cyclization of the investigated aryl-
alkylidenemalonodinitriles, including 2, involves the ipso elec-
trophilic attack of the protonated nitrile group on the benzene
ring with the formation of a spirobenzenium cation 20. The alkyl
shift (200) gives 2%, which after losing the proton tautomerizes to
3 (Scheme 1).
The essential problem of the strategy was an issue of how the
ring closure proceeds towards the naphthalene system. In the case
of monosubstituted dinitriles (e.g., 2), the cyclization might involve
an annulation to the phenyl or substituted-phenyl group.
Depending on the substituent’s character, there is also a possibility
of simultaneous annulation on both pathwaysdas outlined in
Scheme 2. To study the preferences of the attack of the protonated
nitrile group on the benzene system ‘A’ or ‘B’ (path ‘a’ or ‘b’, re-
rivatives of
a-(substituted-phenyl)naphthalenes from 2,2-diphe-
nylethanals and 1,1-diphenylpropan-2-ones.10 The synthetic route
involved the condensation of the carbonyl compounds with
malonodinitrile and cyclization of the obtained aryl-alkylidene-
malonodinitriles in concentrated sulfuric acid. The same strategy
spectively) we have synthesized several
acetaldehydes and acetones having methyl groups or chlorine
a,a-diphenyl-substituted
* Corresponding author. Tel.: þ48 126632904; fax: þ48 126340515.
E-mail address: kozik@chemia.uj.edu.pl (B. Kozik).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.067

B. Kozik et al. / Tetrahedron 64 (2008) 6452–6460
6453
CN
H+
CN
O
NC
2
CN
1
4'
3'
2'
5'
6'
1,2-alkyl
shift
1'
H
5
8
4
3
+
+
6
7
+
- H+
2
CN
CN
CN
CN
HN
2'
HN
2''
1
NH
NH2
3
2'''
Scheme 1.
of our knowledge, with exception of 4a, there were no other reports
on condensation of the carbonyl compounds investigated here with
malonodinitrile.15 The above-mentioned condensation of aldehyde
4a had been catalyzed by potassium fluoride and gave 5a in mod-
erate yield.15 We carried out the same reaction in boiling benzene
with continuous removal of water and in the presence of NH4OAc/
AcOH as a catalyst. Due to the difficulties in isolation of dinitrile 5a,
we decided to find a more effective method. Thus, brief heating of
diphenylacetaldehyde (4a) with malonodinitrile in anhydrous
ethanol and with a catalytic amount of piperidine gave 5a in 78%
yield.10 Previously, we reported the condensation of 1,1-diphenyl-
acetone (4b) with NH4OAc/AcOH as a catalyst.10 The currently
presented reaction of 4b, carried out with addition of piperidine,
did not give much better results (32%). A low yield, in spite of rel-
atively prolonged condensation time under standard conditions,
might be caused by the steric hindrance imposed on the carbonyl
function by the phenyl group and partial degradation of the prod-
uct during extended heating time. Cyclization of 5a and 5b in
concentrated sulfuric acid occurred in a straightforward manner to
give aminonitriles 6a and 6b, respectively, in high yields. From all
aminonitriles reported in this paper, only 6b was synthesized be-
fore.16 However, the mentioned method seemed to be more com-
plex in comparison with our synthetic strategy.
R1
path "a"
A
R2
R
B
NC
H+
CN
path "b"
path "a"
path "b"
R1
R2
B
A
R2
R1
R
R
A
B
CN
CN
NH2
NH2
R = H, CH3
R1, R2 = H, CH3, Cl
Scheme 2.
atoms located exclusively in the para position of one or both ben-
zene rings.
Diphenylacetaldehyde (4a) and 1,1-diphenylacetone (4b) were
the only commercially available substrates. To investigate the scope
of the synthesis of 1-amino-4-arylnaphthalene-2-carbonitriles,
having the general structure of 6a,b, we obtained methyl (1, 7,
Scheme 4) and chloro (10, 13, Scheme 5) derivatives of 4a,b. Un-
fortunately, the syntheses and purification of these apparently
simple compounds encountered unexpected difficulties and re-
quired several attempts. We did not manage to work out the gen-
eral method for synthesis of either the aldehydes 1 and 7 or ketones
10 and 13.
Monosubstituted aldehydes, which have a methyl group (7a) or
a chlorine atom (13a) in the para position of the benzene ring, were
prepared by oxidation of 4-methyl- or 4-chlorostilbene, re-
spectively, with perbenzoic acid, followed by rearrangement of the
resulting oxiranes using bismuth(III) perchlorate oxide hydrate
(BiOClO4$xH2O) as a catalyst.17 Similarly, pinacol rearrangement of
1,2-bis(4-methylphenyl)ethane-1,2-diol in glacial acetic acid,
In the beginning we focused on verifying the usefulness of this
method in the synthesis of 1-amino-4-phenylnaphthalene-2-car-
bonitrile system. As starting materials diphenylacetaldehyde (4a)
and 1,1-diphenylacetone (4b) were used (Scheme 3).14 To the best
i
R
ii
R
R
O
CN
NC
CN
NH2
6a: R=H, 90%
6b: R=CH3, 90%
4a: R=H
4b: R=CH3
5a: R=H, 78%
5b: R=CH3, 32%
Scheme 3. Reagents and conditions: (i) CH2(CN)2, piperidine, EtOH, 5 min (4a) or
CH2(CN)2, piperidine–AcOH/NH4OAc, C6H6, 15 h (4b); (ii) concd H2SO4, ꢀ15 ꢁC/
ꢀ5 ꢁC, 1 h.
G
G
G
yield
R
G
2, 8
3, 9
H
H
CH3
CH3
H
H
1-3
7-9a
7-9b
7-9c
45% 71%
41% 79%
49% 60%
44% 77%
i
ii
R
R
R
O
CN
NC
CN
CH3 CH3
NH2
1, 7
2, 8
3, 9
Scheme 4. Reagents and conditions: (i) CH2(CN)2, piperidine–AcOH/NH4OAc, C6H6, 5–17 h; (ii) concd H2SO4, ꢀ15 ꢁC/ꢀ5 ꢁC, 60–75 min.

6454
B. Kozik et al. / Tetrahedron 64 (2008) 6452–6460
Cl
method for the condensation involving heating of the appropriate
Cl
Cl
aldehyde or ketone with malonodinitrile in benzene in the pres-
ence of piperidine–AcOH/NH4OAc as a catalyst. In contrast to 4b,
similar carbonyl compounds (1, 7c, 10b and 13b) in the same con-
ditions were condensed with significantly higher yields. As a sol-
vent we chose benzene instead of toluene to reduce formation of
tar substances and other possible side products.
i
R
ii
Cl
R
R
O
Cl
CN
Cl
NC
CN
NH2
The condensation step was followed by cyclization of the
obtained aryl-ylidenemalonodinitriles in concentrated sulfuric
acid. The pathways of ring closure of the dinitriles 2, 8, 11 and 14
were more complex in comparison with the straightforward cy-
clization of dinitriles 5a and 5b. The unusual mechanism of the
cyclization and quasi-aromatic rearrangement has already been
shown on Scheme 1. It is similar to the mechanism suggested in our
recent reports that had assumed the presence of the allylic-type
carbocation in the alkyl-shift stage.11,13 However, rearrangements
discussed here appear to be the first example of cyclization in-
volving the benzylic-type carbocation. The stability of this carbo-
cation may have contributed to the relatively high yield of obtained
aminonitriles. Cyclizations of the methyl- or dimethyl-substituted
ylidenemalonodinitriles 8a–c proceeded in the same way as pre-
viously discussed cyclization of 2 (Scheme 4). In all cases the re-
action involved only annulation of a methyl-substituted benzene
ring. We obtained rearranged aminonitriles 3 and 9a–c as single
products in good yields.
10a: R=H
11a: R=H, 28%
11b: R=CH3, 35%
12a: R=H, 62%
12b: R=CH3, 78%
10b: R=CH3
Scheme 5. Reagents and conditions: (i) CH2(CN)2, piperidine–AcOH/NH4OAc, C6H6, 6 h
(10a) or 19 h (10b); (ii) concd H2SO4, ꢀ15 ꢁC/ꢀ5 ꢁC, ca. 20 h (11a) or 2.5 h (11b).
catalyzed by sulfuric acid, gave dimethyl derivative 7b in good
yield.18 2,2-Bis(4-chlorophenyl)ethanal (10a) was obtained from
4,40-dichlorobenzophenone and ethyl chloroacetate by Darzens
synthesis.19
Ketones 1 and 13b were synthesized according to the published
procedure, by the
a-bromination of phenylacetone followed by
Friedel–Crafts reaction with toluene or chlorobenzene, re-
spectively.20 Diarylpropanones 7c and 10b were prepared by
pinacol rearrangement18 of appropriate 1,1-diarylpropane-1,2-
diols.21
After their preparation, the carbonyl compounds 1, 7, 10 and 13
were condensed with malonodinitrile. We employed the standard
The position of the methyl group at C-6 of naphthalene moiety 3
was established through 2D NMR experiments. The HMBC spec-
trum of 3 revealed correlation through three bonds between
strongly deshielded C-1 (
C-8 carbon atom (Fig. 1). This proton appeared at
and was coupled to the neighbouring proton connected to C-7 (
d
147.9 ppm) and the proton bonded to the
d
7.70 as a doublet
d
7.28 ppm) with the coupling constant of 8.5 Hz. Furthermore, the
proton bonded to C-7 was also coupled over four bonds to the
proton at C-5 (J¼1.6 Hz). The signal of the proton at C-5 at
d 7.07 had
an unclear multiplet structure and appeared as a broad singlet. All
acquired data indicated the location of the methyl group at the ‘6-
position’ of 3. Moreover, the experimental 1H NMR spectrum of 3
was in agreement with the simulated one.22a The spin systems
involving protons C5–H, C7–H, C8–H, C6–CH3 and HPh were simu-
lated with the spectral analysis routine NUMMRIT22b using the
SpinWorks software.22c The exact structures of the aminonitriles
9a–c were determined by 1D or 2D NMR experiments in compar-
ison with the appropriate spectra of 3.
The second group of ylidenemalonodinitriles investigated in-
cluded chloro- or dichloro-substituted derivatives (14 and 11,
respectively). The dinitriles 11 cyclized with rearrangement in
a similar way to their dimethyl analogues 8b,c (Scheme 5). In
order to obtain 12 in good yields we prolonged the reaction time
to 2.5 h in the case of 12b and approximately to 20 h in the case
of cyclization of 11a to aminonitrile 12a. The slower progress of
the reaction of 11 was primarily caused by the electron with-
drawing character of the chlorine atoms. On the other hand,
noticeably higher rate of the cyclization of 11b might have been
dependent on the more stable protonated form of the dinitrile
11b, which was probably due to the presence of the methyl group
at the sp2 carbon atom (Fig. 2). Higher population of the more
stable carbocation, hypothetically, could be favourable for its
6
7
C
NH2
CN
8
H
1
7.70 ppm
3
147.9 ppm
Figure 1. A part of the HMBC spectrum of 3dcorrelation between the C8–H proton
and C1 carbon atom.
CH3
C
CH3
C
CH3
C
CH3
C
CH3
C
CH3
C
H+
H+
or
C
C
C
C
C
C
N
N
NH
N
HN
H2N
NH HN
N
N
HN
HN
Figure 2. Mono- and diprotonation of dicyanovinyl group.

B. Kozik et al. / Tetrahedron 64 (2008) 6452–6460
6455
Cl
R=H
88%
CN
NH2
15
Cl
i
R
ii
R
O
Cl
Cl
NC
CN
13a: R=H
13b: R=CH3
14a: R=H, 57%
14b: R=CH3, 54%
Cl
R=CH3
overall
yield 85%
CN
CN
NH2
NH2
16b
16a
70 : 30
Scheme 6. Reagents and conditions: (i) CH2(CN)2, piperidine–AcOH/NH4OAc, C6H6, 3 h (14a) or CH2(CN)2, piperidine–AcOH/NH4OAc, toluene, 9 h (14b); (ii) concd H2SO4, ꢀ15 ꢁC/
ꢀ5 ꢁC, 2–3 h.
second protonation. Such a diprotonation of the nitrile group has
already been reported in the case of the similar intramolecular
Houben–Hoesch reaction.23
Precise structural and energetic characterization of 3,3-bis(4-
chlorophenyl)prop-1-ene-1,1-dicarbonitrile (11a) has already been
presented in our earlier report.24 The ratios were estimated from
the 1H NMR spectra, recorded in CDCl3. Calculated proportions, 11a/
11c (3.8:1) and 8b/8d (6.2:1), indicated a possible relationship
between the state of equilibrium and the electron withdrawing
character of substituents in the benzene rings. We also noticed that
the ratio might be dependent on time, which passed since the
sample was dissolved in CDCl3. However, the rough measurements
were performed only for 8b and we did not investigate the subject
in more detail. The tautomerism was observed also for mono-
substituted dinitriles 8a and 14a. In the methyl derivative 8a the
equilibrium was significantly shifted towards the diarylprop-1-
ene-1,1-dicarbonitrile structure.
Furthermore, the aminonitriles 3, 6a, 9a–c, 12a–b and 15 were
evaluated in vitro for growth-inhibiting activity against some
phytopathogenic fungi such as Fusarium culmorum, Penicillium
expansum, Botrytis cinerea and Alternaria species.25 In connection
with our earlier studies on highly active 1-aminonaphthalene-2-
carbonitriles possessing short alkyl groups at the ‘4-position,’26 we
presumed that the analogous 4-phenyl- or 4-aryl-substituted
aminonitriles might also exhibit fungicidal activity. Preliminary
tests of above-mentioned 4-aryl-1-aminonaphthalene-2-carbon-
itriles revealed their diverse biological activity against investigated
fungi. Aminonitrile 6a showed relatively the highest fungistatic
activity. The results for the 6a were compared in Table 1 with the
activity of a commercial fungicidedKaptan 50 WP (a.i. captan
50%).25
Cyclizations of dinitriles 14 possessing the chlorine atom only
in one of the benzene rings confirmed our previous conclusions
about the better stabilized protonated forms of the dinitriles
obtained from the ketones (Scheme 6). Stirring 14a in chilled
concentrated sulfuric acid for 3 h led only to one isomer 15 (88%
yield). On the contrary, analogous cyclization of the dinitrile 14b
gave two products with comparable overall yield. As expected,
the main isomer 16a was formed by annulation to the unsub-
stituted benzene ring of 14b. However, the NMR spectra of the
isolated product revealed also the presence of isomer 16b, having
the chlorine atom in the naphthalene system. That indicates the
attack of the protonated nitrile function of the dinitrile 14b on
the phenyl group deactivated by the chlorine atom. The less se-
lective cyclization of 14b suggests higher reaction rate than in
case of 14a. In conclusion, the methyl group at C-2 carbon atom
of the investigated 3,3-diarylpropene-1,1-dicarbonitriles seems to
be the most probable factor increasing the electrophilicity of the
protonated nitrile group during the rate determining step of
electrophilic substitution. The structure and the ratio of isomers
16a and 16b (70:30) were established from the 1H NMR spec-
trum. Attempts to separate the isomers using chromatographic
methods were not successful.
It is also noteworthy that the dinitriles presented in the report,
obtained during condensations of aldehydes with malonodinitrile,
might occur along with their tautomeric forms (Scheme 7). Co-
existence of similar tautomeric forms in solution was earlier ob-
served also by Zimmerman and co-workers.15 We made an
investigation with special consideration of dinitriles 8b and 11a,
which have the clearest 1H NMR spectra due to the molecule’s
symmetry. Their isomers, respectively, 8d and 11c, arose through
the migration of the carbon–carbon double bond (Scheme 7).
The synthetic strategy presented in this report enables simple,
two-stage synthesis of a-arylnaphthalene systems from a,a-diaryl-
substituted acetaldehydes or acetones. We investigated the possi-
ble ways of ring closure of the diarylalkylidenemalonodinitriles
equipped with methyl groups or chlorine atoms in the benzene
rings. The presented approach might potentially be employed in
the synthesis of some chiral
amino and nitrile functions.
a-arylnaphthalenes having versatile
R1
R1
Table 1
A comparison of the fungistatic activity of 1-amino-4-phenylnaphthalene-2-car-
bonitrile (6a) and the commercial fungicidedcaptan
EC50 [mg/dm3]
R2
NC
CN
R2
NC
CN
Fusarium
culmorum
Alternaria
brassicicola
Botrytis
cinerea
Penicillium
expansum
8b: R1=R2=CH3
8d: R1=R2=CH3
11a: R1=R2=Cl
11c: R1=R2=Cl
6a
93
30
11
11
18
20
45
Captan
743
Scheme 7. Tautomerism of ylidenemalonodinitriles 8b and 11a.

6456
B. Kozik et al. / Tetrahedron 64 (2008) 6452–6460
3. Experimental
113 ꢁC). IR (KBr) 3049, 3029, 2929, 2239 (CN), 1599, 1492, 1454, 965,
745, 701 cmꢀ1 1H NMR (CDCl3)
5.34 (d, 1H, J¼11.1 Hz, Ph2CH),
.
d
3.1. General remarks
7.16–7.18 (m, 4H, Ar–H), 7.32–7.41 (m, 6H, Ar–H), 7.70 (d, 1H,
J¼11.1 Hz, –CH]). 13C NMR (CDCl3)
d 53.3 (Ph2C), 89.1 ((CN)2C]),
Melting points were recorded on Boe¨tius apparatus and are
uncorrected. 1H and 13C NMR spectra were taken on a Bruker AMX
500 instrument at 500 and 125 MHz, respectively, using tetrame-
thylsilane as internal standard. IR spectra were recorded on Bruker
IFS 48FT or Bruker Equinox 55 spectrophotometer. Elemental
analysis was performed on a EuroEA Elemental Analyzer. Thin layer
chromatography was performed on silica plates (Fluka, 0.2 mm)
and column chromatography on silica gel (Fluka, 70–230 mesh).
110.5 (CN), 111.9 (CN), 128.1 (4ꢂCAr), 128.3 (2ꢂCAr), 129.4 (4ꢂCAr),
138.2 (2ꢂCAr), 167.7 (–CH]).
3.2.3. 2-Methyl-3,3-diphenylprop-1-ene-1,1-dicarbonitrile (5b)
Following the method A, 1,1-diphenylacetone (4b) (0.61 g,
2.90 mmol), malonodinitrile (0.21 g, 3.18 mmol), glacial acetic acid
(0.33 g, 5.50 mmol), ammonium acetate (0.11 g, 1.43 mmol), pi-
peridine (78 mg, 0.93 mmol) and benzene (11 mL) were heated for
4 h with continuous water separation. Due to the relatively high
amount of unreacted ketone 4b indicated by TLC, additional por-
tions of malonodinitrile (70 mg, 1.06 mmol), ammonium acetate
(70 mg, 0.91 mmol) and piperidine (34.5 mg, 0.41 mmol) were
added twice during a further 11 h of heating to reflux. After stan-
dard work-up, the crude product was purified by column chro-
matography (toluene/SiO2) to give the dinitrile 5b (242 mg, yield
32.3%) as small, white crystals. Mp 100–101 ꢁC. IR (KBr) 3061, 3029,
2916, 2232 (CN),1580,1498,1454,1367, 745, 714, 695 cmꢀ1. 1H NMR
3.2. Preparation of diarylalkylidenemalonodinitriles 2, 5, 8, 11
and 14
General procedure for the synthesis of 2, 5b, 8, 11 and 14 (method
A). The carbonyl compounds 1, 4b, 7, 10 or 13, malonodinitrile,
glacial acetic acid, ammonium acetate, piperidine and benzene (or
toluene) were heated for 10–17 h (7b: 5 h) with continuous water
separation (Dean–Stark apparatus). The reaction was monitored by
TLC (toluene or chloroform/SiO2) and, if necessary, further portions
of malonodinitrile, ammonium acetate and piperidine were added.
The reaction mixture was washed with water, dried with anhy-
drous magnesium sulfate and the solvent was evaporated in vacuo.
The products 2 and 14b were isolated by vacuum distillation. Other
crude dinitriles were purified by column chromatography and were
usually recrystallized.
(CDCl3)
d
2.23 (s, 3H, –CH3), 5.71 (s, 1H, Ph2CH), 7.14–7.15 (m, 4H,
21.1 (–CH3), 57.1
Ar–H), 7.33–7.40 (m, 6H, Ar–H). 13C NMR (CDCl3)
d
(Ph2C), 88.0 ((CN)2C]), 111.6 (CN), 111.8 (CN), 128.1 (2ꢂCAr), 128.8
(4ꢂCAr), 129.1 (4ꢂCAr), 137.8 (2ꢂCAr), 181.4 (–C(CH3)]). Anal. Calcd
for C18H14N2: C, 83.69; H, 5.46; N, 10.85%. Found: C, 83.45; H, 5.56;
N, 11.09%.
General procedure for the synthesis of 5a and 8b (method B). A
solution of aldehyde 4a or 7b, malonodinitrile and catalytic amount
of piperidine in anhydrous ethanol was heated to reflux for 5 min
and then was slowly cooled in an ice-bath. In case of 5a, colourless
precipitated solid was filtered off and washed with a small amount
of chilled ethanol. Dinitrile 8b was isolated by column chroma-
tography and recrystallized.
3.2.4. 3-(4-Methylphenyl)-3-phenylprop-1-ene-1,1-
dicarbonitrile (8a)
Following the method A, ketone 7a (1.73 g, 8.23 mmol), malo-
nodinitrile (0.60 g, 9.08 mmol), glacial acetic acid (0.42 g,
6.99 mmol), ammonium acetate (0.24 g, 3.11 mmol), piperidine
(0.22 g, 2.58 mmol) and benzene (25 mL) were heated for 5 h with
continuous water separation. The mixture was diluted with ben-
zene (25 mL) and worked up in the usual manner. The crude
product was isolated by column chromatography (CCl4/SiO2) and
recrystallized from cyclohexane to give dinitrile 8a (0.88 g, yield
41.3%) as small, white crystals. Mp 95–97 ꢁC. IR (KBr) 3083, 3057,
3034, 2922, 2859, 2237 (CN), 1606, 1595, 1513, 1493, 1451, 946, 775,
3.2.1. 2-Methyl-3-(4-methylphenyl)-3-phenylprop-1-ene-1,1-
dicarbonitrile (2)
Following the method A, ketone 1 (3.00 g, 13.37 mmol), malo-
nodinitrile (1.02 g, 15.38 mmol), glacial acetic acid (1.50 g,
24.97 mmol), ammonium acetate (0.50 g, 6.49 mmol), piperidine
(0.36 g, 4.23 mmol) and benzene (50 mL) were heated for 4.5 h
with continuous water separation. Then the additional portions of
malonodinitrile (0.30 g, 4.54 mmol), ammonium acetate (0.30 g,
3.89 mmol) and piperidine (0.15 g, 1.76 mmol) were added, and
the mixture was heated to reflux for the next 5 h. After standard
work-up, the residue was distilled in vacuo to give the dinitrile 2
(1.64 g, yield 45.1%) as a thick, yellow oil. Bp 141–144 ꢁC/1 mmHg.
IR (neat) 3061, 3029, 2923, 2232 (CN), 1592, 1511, 1454, 1379,
736, 701 cmꢀ1 1H NMR (CDCl3)
. d 2.36 (s, 3H, CH3), 5.30 (d, 1H,
J¼11.1 Hz, Ar2CH), 7.05–7.06 (m, 2H, Ar–H), 7.13–7.20 (m, 4H, Ar–H),
7.32–7.39 (m, 3H, Ar–H), 7.68 (d, 1H, J¼11.1 Hz, –CH]). 13C NMR
(CDCl3)
d 21.1 (CH3), 53.0 (Ar2C), 88.8 ((CN)2C]), 110.6 (CN), 112.0
(CN), 128.0 (2ꢂCAr), 128.1 (2ꢂCAr), 128.2, 129.4 (2ꢂCAr), 130.1
(2ꢂCAr), 135.2, 138.2, 138.5, 167.9 (–CH]). Anal. Calcd for C18H14N2:
C, 83.69; H, 5.46; N, 10.85%. Found: C, 83.61; H, 5.59; N, 10.89%.
3.2.5. 3,3-Bis(4-methylphenyl)prop-1-ene-1,1-dicarbonitrile (8b)
Method A. Aldehyde 7b (1.00 g, 4.46 mmol), malonodinitrile
(0.32 g, 4.84 mmol), glacial acetic acid (0.23 g, 3.83 mmol), am-
monium acetate (0.19 g, 2.46 mmol), piperidine (112 mg,
1.32 mmol) and benzene (25 mL) were heated for 5 h with con-
tinuous water separation. The mixture was diluted with benzene
(25 mL) and worked up in the usual manner. The crude product was
isolated by column chromatography (toluene/SiO2) and the
obtained yellow thick oil was recrystallized from petroleum ether
(bp 60–90 ꢁC) to give dinitrile 8b (0.59 g, yield 48.6%) as white
crystals. Physical and spectroscopic data were in agreement with
the values reported below (method B).
Method B. A solution of aldehyde 7b (0.50 g, 2.23 mmol),
malonodinitrile (0.16 g, 2.42 mmol) and piperidine (21.5 mg,
0.252 mmol) in anhydrous ethanol (5 mL) was heated to reflux for
5 min. After removal of the solvent in vacuo, the residue was
chromatographed (CCl4/SiO2) and the obtained yellow thick oil was
crystallized from petroleum ether (bp 60–90 ꢁC) to give dinitrile 8b
707 cmꢀ1
Ar–CH3), 5.68 (s, 1H, Ar2CH), 7.02–7.04 (m, 2H, Ar–H), 7.13–7.20 (m,
4H, Ar–H), 7.34–7.40 (m, 3H, Ar–H). 13C NMR (CDCl3)
21.0
. d 2.23 (s, 3H, C–CH3), 2.37 (s, 3H,
1H NMR (CDCl3)
d
(2ꢂCH3, Ar–CH3, ]C–CH3), 56.7 (Ar2C), 87.7 ((CN)2C]), 111.7 (CN),
111.9 (CN), 128.0, 128.6 (2ꢂCAr), 128.7 (2ꢂCAr), 128.9, 129.0 (2ꢂCAr),
129.8 (2ꢂCAr), 134.7, 137.9, 138.0, 181.8 (–C(CH3)]). Anal. Calcd for
C
19H16N2: C, 83.79; H, 5.92; N, 10.29%. Found: C, 83.75; H, 5.96;
N, 10.27%.
3.2.2. 3,3-Diphenylprop-1-ene-1,1-dicarbonitrile (5a)15
Following the method B, diphenylacetaldehyde (4a) (1.14 g,
5.81 mmol), malonodinitrile (0.38 g, 5.81 mmol), piperidine
(34.5 mg, 0.405 mmol) and anhydrous ethanol (5 mL) were heated
to reflux for 5 min, and then slowly cooled in an ice-bath. The
resulting colourless precipitated solid was washed with a small
amount of chilled ethanol. Dinitrile 5a was obtained as small, white
crystals (1.11 g, yield 78.2%). Mp 110–111 ꢁC (Ref. 15: mp 107.5–

B. Kozik et al. / Tetrahedron 64 (2008) 6452–6460
6457
(217.4 mg, yield 35.8%) as white short needles. Mp 110–112 ꢁC. IR
(KBr) 3032, 2950, 2919, 2860, 2234 (CN), 1606, 1510, 1450, 1042,
5.66 mmol), ammonium acetate (0.22 g, 2.85 mmol), piperidine
(232 mg, 2.72 mmol) and benzene (35 mL) were heated for 7 h
with continuous water separation. Due to the relatively high
amount of unreacted ketone 10b indicated by TLC, additional
portions of malonodinitrile (0.24 g, 3.63 mmol), ammonium ac-
etate (0.12 g, 1.16 mmol) and piperidine (121 mg, 1.42 mmol)
were added twice during further 12 h of heating to reflux. After
standard work-up, the crude product was purified by double
column chromatography, using at first toluene/SiO2, then pe-
troleum ether (bp 60–90 ꢁC)–ethyl acetate, 30:1 (v/v)/SiO2. The
dinitrile 11b was obtained as a colourless, very thick oil, which
partially solidified after a few days (0.74 g, yield 35.2%). An an-
alytical sample of 11b was obtained by recrystallization from
ethanol. Mp 87–88.5 ꢁC (small, white crystals). IR (KBr) 3088,
3067, 3049, 2962, 2922, 2852, 2228 (CN), 1588, 1490, 1406, 1089,
1021, 942, 855, 818, 751 cmꢀ1. 1H NMR (CDCl3)
d
2.35 (s, 6H, 2ꢂCH3),
5.25 (d,1H, J¼11.1 Hz, Ar2CH), 7.03–7.05 (m, 4H, Ar–H), 7.17–7.18 (m,
4H, Ar–H), 7.65 (d, 1H, J¼11.1 Hz, –CH]). 13C NMR (CDCl3)
d 21.0
(2ꢂCH3), 52.7 (Ar2C), 88.5 ((CN)2C]), 110.6 (CN), 112.0 (CN), 127.9
(4ꢂCAr), 130.0 (4ꢂCAr), 135.4 (2ꢂCAr), 138.1 (2ꢂCAr), 168.1 (–CH]).
Tautomer of 8b: 3,3-bis(4-methylphenyl)prop-2-ene-1,1-dicarbo-
nitrile (8d). 1H NMR (CDCl3)
d
2.35 (s, 6H, 2ꢂCH3), 4.51 (d, 1H,
J¼9.5 Hz, –CH(CN)2), 5.98 (d, 1H, J¼9.5 Hz, Ar2C]CH), 7.07–7.09 (m,
4H, Ar–H), 7.27–7.29 (m, 4H, Ar–H). Anal. Calcd for C19H16N2: C,
83.79; H, 5.92; N, 10.29%. Found: C, 83.94; H, 5.86; N, 10.44%.
3.2.6. 2-Methyl-3,3-bis(4-methylphenyl)prop-1-ene-1,1-
dicarbonitrile (8c)
Following the method A, ketone 7c (2.06 g, 8.64 mmol), malo-
nodinitrile (0.63 g, 9.54 mmol), glacial acetic acid (0.44 g,
7.32 mmol), ammonium acetate (0.36 g, 4.67 mmol), piperidine
(0.31 g, 3.64 mmol) and benzene (40 mL) were heated for 5.5 h
with continuous water separation. Due to the relatively high
amount of unreacted ketone 7c, indicated by TLC, additional por-
tions of malonodinitrile (0.60 g, 9.08 mmol), ammonium acetate
(0.42 g, 5.45 mmol) and piperidine (233 mg, 2.74 mmol) were
added, and the reaction time was prolonged to 12 h. After standard
work-up, tar substances were removed by flash chromatography
(toluene/SiO2) and the crude product was purified by column
chromatography (petroleum ether (bp 60–90 ꢁC)–ethyl acetate,
25:1 (v/v)/SiO2) to give the dinitrile 8c (1.10 g, yield 44.5%) as very
thick, colourless oil. IR (neat) 3027, 3003, 2952, 2924, 2869, 2232
(CN), 1589, 1512, 1449, 1378, 1189, 1121, 1022, 843, 819, 765,
1012, 829, 792, 750, 542, 494 cmꢀ1
3H, CH3), 5.63 (s, 1H, Ar2CH), 7.05–7.07 (m, 4H, Ar–H), 7.36–7.39
(m, 4H, Ar–H). 13C NMR (CDCl3)
21.0 (CH3), 55.7 (Ar2C), 88.7
. d 2.20 (s,
1H NMR (CDCl3)
d
((CN)2C]), 111.3 (CN), 111.5 (CN), 129.5 (4ꢂCAr), 130.0 (4ꢂCAr),
134.6 (2ꢂCAr), 135.8 (2ꢂCAr), 179.7 (–C(CH3)]). Anal. Calcd for
C18H12Cl2N2: C, 66.07; H, 3.70; N, 8.56%. Found: C, 66.20; H,
3.59; N, 8.52%.
3.2.9. 3-(4-Chlorophenyl)-3-phenylprop-1-ene-1,1-
dicarbonitrile (14a)
Following the method A, aldehyde 13a (0.67 g, 2.90 mmol),
malonodinitrile (0.32 g, 4.84 mmol), glacial acetic acid (0.21 g,
3.50 mmol), ammonium acetate (0.18 g, 2.34 mmol), piperidine
(0.20 g, 2.30 mmol) and benzene (20 mL) were heated for 3 h with
continuous water separation. The mixture was diluted with ben-
zene (25 mL) and worked up in the usual manner. The dinitrile 14a
was isolated by column chromatography (petroleum ether (bp 60–
90 ꢁC)–ethyl acetate, 15:1 (v/v)/SiO2) as white small crystals (0.46 g,
yield 56.8%). Mp 96–98.5 ꢁC. IR (KBr) 3039, 2920, 2853, 2237 (CN),
1606, 1491, 1450, 1408, 1092, 1015, 753, 701 cmꢀ1. 1H NMR (CDCl3)
737 cmꢀ1. 1H NMR (CDCl3)
CH3), 5.62 (s, 1H, Ar2CH), 7.01–7.03 (m, 4H, Ar–H), 7.16–7.18 (m, 4H,
Ar–H). 13C NMR (CDCl3)
d
2.21 (s, 3H, CCH3), 2.36 (s, 6H, 2ꢂAr–
d
21.0 (2ꢂAr–CH3, CCH3), 56.4 (Ar2C), 87.5
((CN)2C]), 111.7 (CN),111.9 (CN), 128.6 (4ꢂCAr), 129.7 (4ꢂCAr), 135.0
(2ꢂCAr), 137.9 (2ꢂCAr), 182.0 (–C(CH3)]). Anal. Calcd for C20H18N2:
C, 83.88; H, 6.34; N, 9.78%. Found: C, 83.86; H, 6.39; N, 9.78%.
d
5.30 (d, 1H, J¼10.8 Hz, Ar2CH), 7.09–7.11 (m, 2H, Ar–H), 7.13–7.15
(m, 2H, Ar–H), 7.35–7.41 (m, 5H, Ar–H), 7.63 (d, 1H, J¼10.8 Hz,
–CH]). 13C NMR (CDCl3)
52.6 (Ar2C), 89.6 ((CN)2C]), 110.4 (CN),
3.2.7. 3,3-Bis(4-chlorophenyl)prop-1-ene-1,1-dicarbonitrile (11a)24
Following the method A, aldehyde 10a (1.58 g, 5.96 mmol),
malonodinitrile (0.47 g, 7.12 mmol), glacial acetic acid (0.34 g,
5.66 mmol), ammonium acetate (0.22 g, 2.85 mmol), piperidine
(0.23 g, 2.70 mmol) and benzene (35 mL) were heated for 6 h with
continuous water separation. The mixture was diluted with ben-
zene (20 mL) and worked up in the usual manner. The dinitrile 11a
was purified by column chromatography (CCl4/SiO2) to give a red
oil, which slowly solidified (0.52 g, yield 27.8%). An analytical
sample of 11a was obtained by double recrystallization from pe-
troleum ether (bp 60–90 ꢁC). Mp 101.5–103.5 ꢁC (yellow plates). IR
(KBr) 3087, 3055, 3032, 2921, 2853, 2238 (CN), 1909, 1606, 1489,
d
111.8 (CN), 128.0 (2ꢂCAr), 128.5, 129.4 (2ꢂCAr), 129.5 (2ꢂCAr), 129.6
(2ꢂCAr), 134.4, 136.8, 137.9, 166.9 (–CH]). Anal. Calcd for
C17H11ClN2: C, 73.25; H, 3.98; N, 10.05%. Found: C, 73.07; H, 3.84; N,
10.05%.
3.2.10. 3-(4-Chlorophenyl)-2-methyl-3-phenylprop-1-ene-1,1-
dicarbonitrile (14b)
Ketone 13b (5.70 g, 23.3 mmol), malonodinitrile (1.85 g,
28.0 mmol), glacial acetic acid (1.50 g, 25.0 mmol), piperidine
(0.85 g, 10.0 mmol) and toluene (20 mL) were heated for 5 h with
continuous water separation. Then the additional portions of
malonodinitrile (1.85 g, 28.0 mmol) and glacial acetic acid (2.00 g,
33.3 mmol) and also ammonium acetate (1.00 g, 13.0 mmol) were
added, and the mixture was heated to reflux for next 4 h. The
reaction mixture was washed with water, dried with anhydrous
magnesium sulfate and the solvent was evaporated. The residue
was distilled in vacuo to give the dinitrile 14b (3.71 g, yield
54.4%) as a thick, yellow oil. An analytical sample of 14b was
obtained by column chromatography (cyclohexane–ethyl acetate,
15:1 (v/v)/SiO2). Bp 182–187 ꢁC/2 mmHg. IR (neat) 3029, 2929,
1405, 1090, 1011, 933, 828, 800, 771, 551, 525, 492 cmꢀ1 1H NMR
.
(CDCl3)
d
5.28 (d, 1H, J¼11.0 Hz, Ar2CH), 7.07–7.09 (m, 4H, Ar–H),
7.36–7.38 (m, 4H, Ar–H), 7.58 (d, 1H, J¼11.0 Hz, –CH]). 13C NMR
(CDCl3)
d 52.0 (Ar2C), 90.1 ((CN)2C]), 110.2 (CN), 111.6 (CN), 129.3
(4ꢂCAr), 129.8 (4ꢂCAr), 134.7 (2ꢂCAr), 136.4 (2ꢂCAr), 166.0 (–CH]).
Tautomer of 11a: 3,3-bis(4-chlorophenyl)prop-2-ene-1,1-dicarbo-
nitrile (11c).24 1H NMR (CDCl3)
d
4.44 (d, 1H, J¼9.3 Hz, –CH(CN)2),
6.06 (d, 1H, J¼9.3 Hz, Ar2C]CH), 7.14–7.17 (m, 4H, Ar–H), 7.32–7.34
(m, 2H, Ar–H), 7.48–7.50 (m, 2H, Ar–H). 13C NMR (CDCl3)
23.0
d
(–CH(CN)2), 111.4 (Ar2C]CH), 112.5 (CN), 129.0 (2ꢂCAr), 129.1
(2ꢂCAr), 129.9 (2ꢂCAr), 130.3 (2ꢂCAr), 134.1, 136.0,136.1, 136.8,149.6
(Ar2C]).
2848, 2232 (CN), 1592, 1492, 1454, 1373, 833, 739, 701 cmꢀ1
NMR (CDCl3) 2.22 (s, 3H, –CH3), 5.67 (s, 1H, Ar2CH), 7.07–7.10
(m, 2H, Ar–H), 7.11–7.13 (m, 2H, Ar–H), 7.33–7.41 (m, 5H, Ar–H).
13C NMR (CDCl3)
21.0 (CH3–), 56.3 (Ar2C), 88.3 ((CN)2C]), 111.5
.
1H
d
d
3.2.8. 3,3-Bis(4-chlorophenyl)-2-methylprop-1-ene-1,1-
dicarbonitrile (11b)
Following the method A, ketone 10b (1.79 g, 6.41 mmol),
malonodinitrile (0.47 g, 7.12 mmol), glacial acetic acid (0.34 g,
(CN), 111.7 (CN), 128.4, 128.7 (2ꢂCAr), 129.3 (2ꢂCAr), 129.4 (2ꢂCAr),
130.1 (2ꢂCAr), 134.2, 136.3, 137.3, 180.7 (–C(CH3)]). Anal. Calcd
for C18H13ClN2: C, 73.85; H, 4.48; N, 9.57%. Found: C, 73.86; H,
4.45; N, 9.43%.

6458
B. Kozik et al. / Tetrahedron 64 (2008) 6452–6460
3.3. Preparation of 1-amino-4-arylnaphthalene-2-
carbonitriles 3, 6, 9, 12, 15 and 16
aminonitrile 9a (245.3 mg, yield 79.2%) as white, short needles. Mp
172–174 ꢁC. IR (KBr) 3431, 3325, 3237 (nN–H), 3055, 3036, 2973,
2916, 2208 (CN), 1645 (dN–H), 1623, 1598, 1569, 1503, 1432, 1247,
1076, 1027, 891, 815, 781, 768, 705, 683, 639 cmꢀ1. 1H NMR (CDCl3)
3.3.1. 1-Amino-3,6-dimethyl-4-phenylnaphthalene-2-carbonitrile
(3)10
d
2.42 (s, 3H, CH3), 5.08 (br s, 2H, NH2), 7.24 (s, 1H, C3–H), 7.38–
Dinitrile 2 (0.62 g, 2.28 mmol) was dissolved in chilled con-
centrated sulfuric acid (9 mL). After stirring at ꢀ5 to ꢀ15 ꢁC for 1 h,
the resulting brown solution was poured onto crushed ice (ca. 80 g).
Obtained pink solid was filtered off and washed with saturated
NaHCO3 solution. Crude product was purified by column chroma-
tography (toluene/SiO2) to give aminonitrile 3 (0.44 g, yield 71%) as
beige small crystals. An analytical sample of 3 was obtained by
crystallization from cyclohexane. Mp 117–119 ꢁC. IR (KBr) 3457,
3372, 3254 (nN–H), 3054, 3023, 2920, 2851, 2199 (CN), 1652 (dN–H),
1623, 1574, 1506, 1440, 1369, 1257, 1159, 1071, 815, 776, 722,
7.43 (m, 4H, 3ꢂHPh, C7–H), 7.46–7.49 (m, 2H, 2ꢂHPh), 7.62 (s, 1H,
C5–H), 7.77 (d, 1H, J¼8.6 Hz, C8–H). 13C NMR (CDCl3)
d 21.8 (CH3),
88.6 (C2), 118.7 (CN), 120.2, 121.3, 126.3, 126.8, 127.3, 128.2, 128.4
(2ꢂCPh), 130.1 (2ꢂCPh), 130.6, 134.4, 139.2, 139.5, 147.6 (C1). Anal.
Calcd for C18H14N2: C, 83.69; H, 5.46; N, 10.85%. Found: C, 83.61; H,
5.59; N, 10.89%.
3.3.5. 1-Amino-6-methyl-4-(4-methylphenyl)naphthalene-2-
carbonitrile (9b)
Dinitrile 8b (145.9 mg, 0.536 mmol) was dissolved in chilled
concentrated sulfuric acid (7 mL). After stirring at about ꢀ15 ꢁC for
1 h, the resulting brown solution was poured onto crushed ice (ca.
60 g). The obtained suspension was neutralized with aq NaOH,
diluted with 50 mL of water, extracted with chloroform, dried over
anhydrous magnesium sulfate and the solvent was removed under
reduced pressure. Crude product was purified by column chroma-
tography (toluene/SiO2) to give aminonitrile 9b (87.9 mg, yield
60.3%) as white small crystals. An analytical sample of 9b was
obtained by vacuum sublimation. Mp 182.5–183.5 ꢁC (white, short
needles). IR (KBr) 3467, 3375, 3251 (nN–H), 3025, 2923, 2854, 2203
(CN), 1650 (dN–H), 1569, 1506, 1442, 1244, 1025, 880, 810, 768, 724,
695 cmꢀ1. 1H NMR (CDCl3)
d 2.27 (s, 3H, C3–CH3), 2.35 (s, 3H, C6–
CH3), 5.08 (br s, 2H, NH2), 7.07 (mc, 1H, C5–H), 7.17–7.20 (m, 2H,
C20–H, C60–H), 7.28 (dd, 1H, J¼8.5, 1.6 Hz, C7–H), 7.41–7.45 (m, 1H,
C40–H), 7.47–7.51 (m, 2H, C30–H, C50–H), 7.70 (d, 1H, J¼8.5 Hz, C8–
H). 13C NMR (CDCl3)
d 19.5 (C3–CH3), 21.9 (C6–CH3), 91.3 (C2), 118.4
(CN), 118.5, 120.8, 126.5, 127.2 (2ꢂC), 128.6 (2ꢂCPh), 128.9, 130.7
(2ꢂCPh), 132.5, 135.5, 138.9, 139.1, 147.9 (C1).
3.3.2. 1-Amino-4-phenylnaphthalene-2-carbonitrile (6a)
Dinitrile 5a (113 mg, 0.463 mmol) was dissolved in chilled
concentrated sulfuric acid (3 mL). After stirring at 0 ꢁC for 1 h, the
resulting brown solution was poured onto crushed ice (ca. 40 g).
Precipitated solid was filtered off and washed with saturated
NaHCO3 solution to give aminonitrile 6a (102 mg, yield 90.3%) as
small, light yellow crystals. An analytical sample of 6a was obtained
by sublimation in vacuo. Mp 116–117 ꢁC. IR (KBr) 3500, 3356 (nN–H),
3080, 3049, 3023, 2214 (CN), 1642 (dN–H), 1601, 1564, 1510, 1450,
682, 625 cmꢀ1. 1H NMR (CDCl3)
d 2.42 (s, 3H, C6–CH3), 2.44 (s, 3H,
C40–CH3), 5.05 (br s, 2H, NH2), 7.21 (s, 1H, C3–H), 7.28 (br s, 4H, Ar–
H), 7.37 (dd, 1H, J¼8.5, 1.5 Hz, C7–H), 7.63 (mc, 1H, C5–H), 7.76 (d,
1H, J¼8.6 Hz, C8–H). 13C NMR (CDCl3)
d
21.2 (C40–CH3), 21.8 (C6–
CH3), 88.8 (C2), 118.7 (CN), 120.3, 121.3, 126.4, 126.7, 128.2, 129.1
(2ꢂCAr), 129.9 (2ꢂCAr), 130.7, 134.6, 136.6, 137.0, 139.1, 147.4 (C1).
Anal. Calcd for C19H16N2: C, 83.79; H, 5.92; N, 10.29%. Found: C,
83.73; H, 6.06; N, 10.26%.
1262, 883, 761 cmꢀ1. 1H NMR (CDCl3)
d 5.14 (s, 2H, NH2), 7.28 (s, 1H,
C3–H), 7.39–7.43 (m, 3H, HPh), 7.46–7.48 (m, 2H, HPh), 7.52–7.57 (m,
2H, C6–H, C7–H), 7.84–7.90 (m, 2H, C5–H, C8–H). 13C NMR (CDCl3)
d
89.5 (C2), 118.5 (CN), 121.4, 122.1, 126.2, 126.6, 127.2, 127.4, 128.4
3.3.6. 1-Amino-3,6-dimethyl-4-(4-methylphenyl)naphthalene-2-
carbonitrile (9c)
(2ꢂCPh), 128.9, 130.1 (2ꢂCPh), 131.2, 134.3, 139.4, 147.7 (C1). Anal.
Calcd for C17H12N2: C, 83.58; H, 4.95; N, 11.47%. Found: C, 83.38; H,
5.04; N, 11.32%.
A solution of dinitrile 8c (156.9 mg, 0.548 mmol) in 0.3 mL of
acetone was added to chilled concentrated sulfuric acid (6 mL).
After stirring at ꢀ15 ꢁC for 1 h, the resulting brown solution was
poured onto crushed ice (ca. 60 g). The obtained suspension was
neutralized with aq NaOH, extracted with chloroform, dried over
anhydrous magnesium sulfate and the solvent was removed under
reduced pressure. Crude product was purified by column chroma-
tography (toluene/SiO2) to give aminonitrile 9c (121.2 mg, yield
77.3%) as light beige small crystals. Mp 169.5–170 ꢁC. IR (KBr) 3465,
3372, 3254 (nN–H), 3028, 2916, 2852, 2199 (CN), 1651 (dN–H), 1620,
1572, 1503, 1439, 1369, 1252, 1157, 1072, 812, 776, 772, 734 cmꢀ1. 1H
3.3.3. 1-Amino-3-methyl-4-phenylnaphthalene-2-
carbonitrile (6b)16
Dinitrile 5b (115 mg, 0.445 mmol) was dissolved in chilled
concentrated sulfuric acid (3 mL). After stirring at 0 ꢁC for 1 h, the
resulting green solution was poured onto crushed ice (ca. 40 g).
Precipitated solid was filtered off and washed with saturated
NaHCO3 solution to give aminonitrile 6b (104 mg, yield 90.4%) as
small, white crystals. An analytical sample of 6b was obtained by
vacuum sublimation. Mp 169–171 ꢁC (the mp of 6b is not given in
Ref. 16). IR (KBr) 3469, 3375 (nN–H), 3249, 3055, 3023, 2201 (CN),
NMR (CDCl3)
d 2.27 (s, 3H, C3–CH3), 2.35 (s, 3H, C6–CH3), 2.46 (s,
3H, C40–CH3), 5.05 (br s, 2H, NH2), 7.06–7.08 (m, 2H, Ar–H), 7.12 (s,
1H, C5–H), 7.26–7.29 (m, 3H, 2ꢂAr–H, C7–H), 7.69 (d, 1H, J¼8.6 Hz,
1645 (dN–H), 1601, 1567, 1506, 1440, 1374, 1259, 761, 705, 761 cmꢀ1
1H NMR (CDCl3)
2.30 (s, 3H, CH3), 5.12 (s, 2H, NH2), 7.19–7.21 (m,
.
d
C8–H). 13C NMR (CDCl3) 19.5 (C3–CH3), 21.3 (C40–CH3), 21.8 (C6–
d
2H, HPh), 7.34 (dd, 1H, J¼8.7, 1.5 Hz, C5–H), 7.41–7.50 (m, 5H, C6–H,
CH3), 91.4 (C2), 118.4 (CN), 118.5, 120.8 (C8), 126.5, 127.1, 129.0, 129.3
(2ꢂCAr), 130.6 (2ꢂCAr), 132.6, 135.7, 135.8, 136.8, 139.0, 147.8 (C1).
Anal. Calcd for C20H18N2: C, 83.88; H, 6.34; N, 9.78%. Found: C,
83.65; H, 6.52; N, 9.65%.
C7–H, HPh), 7.81 (dd, 1H, J¼8.5, 1.5 Hz, C8–H). 13C NMR (CDCl3)
d
19.4 (–CH3), 92.1 (C2), 118.1 (CN), 120.3, 120.9, 125.1, 127.3,
127.4, 128.6 (2ꢂCPh), 128.8, 129.5, 130.7 (2ꢂCPh), 132.4, 135.3, 138.8,
147.4 (C1).
3.3.7. 1-Amino-6-chloro-4-(4-chlorophenyl)naphthalene-2-
carbonitrile (12a)
3.3.4. 1-Amino-6-methyl-4-phenylnaphthalene-2-carbonitrile (9a)
Dinitrile 8a (309.8 mg, 1.20 mmol) was dissolved in chilled
concentrated sulfuric acid (15 mL). After stirring at ꢀ5 to ꢀ15 ꢁC
for 75 min, the resulting brown solution was poured onto crushed
ice (ca. 80 g). The obtained suspension was neutralized with aq
NaOH, extracted with chloroform, dried over anhydrous magne-
sium sulfate and the solvent was removed under reduced pressure.
Crude product was purified by vacuum sublimation to give
Dinitrile 11a (153.4 mg, 0.490 mmol) was dissolved in chilled
concentrated sulfuric acid (7 mL). Reaction was monitored by TLC
(chloroform/SiO2 and toluene/SiO2). The mixture was stirred at ꢀ15
to ꢀ10 ꢁC for 3.5 h, then left overnight at about ꢀ15 ꢁC. The
resulting solution was poured onto crushed ice (ca. 60 g). The
obtained suspension was neutralized with aq NaOH, extracted with
chloroform, dried over anhydrous magnesium sulfate and the

B. Kozik et al. / Tetrahedron 64 (2008) 6452–6460
6459
solvent was removed under reduced pressure. Crude product was
purified by column chromatography (toluene–ethyl acetate, 4:1
(v/v)/SiO2) to give aminonitrile 12a (94.7 mg, yield 61.7%) as white
small crystals. Mp 264.5–266 ꢁC. IR (KBr) 3466, 3372, 3250 (nN–H),
3088, 2208 (CN), 1651 (dN–H), 1607, 1559, 1494, 1440, 1284, 1116,
(ca. 100 g). The obtained suspension was neutralized with aq NaOH,
extracted with chloroform, dried over anhydrous magnesium sul-
fate and the solvent was removed under reduced pressure. Crude
product was purified by column chromatography (toluene/SiO2) to
give mixture of aminonitriles 16a and 16b (70:30, 172.5 mg, overall
yield 84.7%) as beige small crystals. IR (KBr) 3450, 3369, 3262
1091, 1011, 888, 822, 809, 526 cmꢀ1. 1H NMR (DMSO-d6)
d 7.11 (br s,
2H, NH2), 7.33 (s, 1H, C3–H), 7.42–7.44 (m, 2H, Ar–H), 7.54–7.56 (m,
2H, Ar–H), 7.58–7.60 (m, 2H, C5–H, C7–H), 8.47 (d, 1H, J¼9.8 Hz, C8–
(
nN–H), 3067, 3029, 2848, 2201 (CN), 1649 (dN–H), 1567, 1498, 1442,
1373,1254, 827, 764, 701 cmꢀ1. Compound 16a: 1H NMR (DMSO-d6)
2.15 (s, 3H, CH3), 6.84 (br s, 2H, NH2), 7.12–7.13 (m, 1H, C5–H),
7.20–7.23 (m, 2H, HPh), 7.43–7.49 (m, 2H, C6–H, C7–H), 7.54–7.56
(m, 2H, HPh), 8.34–8.35 (m, 1H, C8–H). 13C NMR (DMSO-d6)
19.1
H). 13C NMR (DMSO-d6)
d
86.5 (C2), 118.3 (CN), 120.3, 124.0, 125.2,
d
125.8, 126.1, 128.5 (2ꢂCAr), 129.0, 131.5 (2ꢂCAr), 132.1, 134.3, 134.4,
137.2, 149.7 (C1). Anal. Calcd for C17H10Cl2N2: C, 65.20; H, 3.22; N,
8.94%. Found: C, 65.45; H, 3.55; N, 8.80%.
d
(CH3), 88.4 (C2), 118.1 (CN), 120.1, 123.1 (C8), 124.5, 124.9, 125.6 (C5),
128.5 (2ꢂCAr), 129.1, 131.9, 132.1, 132.5 (2ꢂCAr), 134.4, 137.4, 150.1
3.3.8. 1-Amino-6-chloro-4-(4-chlorophenyl)-3-
methylnaphthalene-2-carbonitrile (12b)
(C1). 16b: 1H NMR (DMSO-d6)
d 2.15 (s, 3H, CH3), 6.94 (br s, 2H,
NH2), 7.05 (d, 1H, J¼2.2 Hz, C5–H), 7.19–7.21 (m, 2H, C20–H, C60–H),
Dinitrile 11b (217.0 mg, 0.663 mmol) was dissolved in chilled
concentrated sulfuric acid (10 mL). Reaction was monitored by TLC
(toluene/SiO2). The mixture was stirred at ꢀ15 to ꢀ10 ꢁC for 2.5 h.
The resulting solution was poured onto crushed ice (ca. 100 g). The
obtained suspension was neutralized with aq NaOH, extracted with
chloroform, dried over anhydrous magnesium sulfate and the sol-
vent was removed under reduced pressure. Crude product was
purified by column chromatography (chloroform/SiO2) to give
aminonitrile 12b (168.1 mg, yield 77.5%) as white small crystals. An
analytical sample of 12b was obtained by recrystallization from
toluene. Mp 194–195.5 ꢁC (white short needles). IR (KBr) 3470,
3370, 3251 (nN–H), 2958, 2918, 2853, 2204 (CN), 1649 (dN–H), 1607,
1566, 1494, 1436, 1363, 1280, 1247, 1091, 1014, 942, 878, 815, 765,
7.43–7.49 (m, 2H, C7–H, C40–H), 7.50–7.53 (m, 2H, C30–H, C50–H),
8.39 (d, 1H, J¼9.0 Hz, C8–H). 13C NMR (DMSO-d6)
d 19.2 (CH3), 89.0
(C2), 117.8, 118.6 (CN), 124.4 (C5), 124.6 (C7), 125.4, 125.6 (C8), 127.4
(C40), 128.7 (2ꢂCPh), 130.5 (2ꢂCPh), 133.9, 134.0, 135.7, 137.8, 149.8
(C1). Anal. Calcd for C18H13ClN2: C, 73.85; H, 4.48; N, 9.57%. Found:
C, 73.64; H, 4.43; N, 9.30%.
Acknowledgements
The support of this research by the Jagiellonian University
within project No. DS 74 is gratefully acknowledged.
References and notes
731 cmꢀ1. 1H NMR (DMSO-d6)
d 2.15 (s, 3H, C3–CH3), 6.98 (br s, 2H,
NH2), 7.03 (d, 1H, J¼2.2 Hz, C5–H), 7.22–7.25 (m, 2H, C20–H, C60–H),
1. Pu, L. Chem. Rev. 1998, 98, 2405–2494.
7.47 (dd, 1H, J¼8.9, 2.1 Hz, C7–H), 7.56–7.58 (m, 2H, C30–H, C50–H),
2. Lloyd-Williams, P.; Giralt, E. Chem. Soc. Rev. 2001, 30, 145–157.
3. (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57, 3809–3844; (b) Noyori, R.
Chem. Soc. Rev. 1989, 18, 187–208.
8.40 (d, 1H, J¼9.0 Hz, C8–H). 13C NMR (DMSO-d6)
d 19.2 (CH3), 89.0
(C2), 117.7, 118.6 (CN), 124.0, 124.1, 124.7, 125.7, 128.8 (2ꢂCAr), 132.3,
4. Wallace, T. W. Org. Biomol. Chem. 2006, 4, 3197–3210.
´
132.4 (2ꢂCAr), 134.1, 134.3, 135.5, 136.6, 150.0 (C1). Anal. Calcd for
5. Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102,
1359–1469.
C
18H12Cl2N2: C, 66.07; H, 3.70; N, 8.56%. Found: C, 66.09; H, 3.70; N,
6. (a) Cammidge, A. N.; Crepy, K. V. L. Tetrahedron 2004, 60, 4377–4386; (b)
Hattori, T.; Takeda, A.; Yamabe, O.; Miyano, S. Tetrahedron 2002, 58, 233–238
and references cited therein; (c) Aoyagi, N.; Ohwada, T.; Izumi, T. Tetrahedron
Lett. 2003, 44, 8269–8272; (d) Alexakis, A.; Benhaim, C. Eur. J. Org. Chem. 2002,
3221–3236.
7. (a) Ward, R. S. Nat. Prod. Rep. 1999, 16, 75–96; (b) Whiting, D. A. Nat. Prod. Rep.
1990, 7, 349–364.
8. (a) Yamamoto, T.; Maruyama, T.; Zhou, Z.; Ito, T.; Fukada, T.; Yoneda, Y.; Begum,
F.; Ikeda, T.; Sasaki, S.; Takezoe, H.; Fukada, A.; Kubota, K. J. Am. Chem. Soc. 1994,
116, 4832–4845; (b) Papillon, J.; Schulz, E.; Gelinas, S.; Lessard, J.; Lemaire, M.
Synth. Met. 1998, 96, 155–160.
8.46%.
3.3.9. 1-Amino-4-(4-chlorophenyl)naphthalene-2-carbonitrile (15)
Dinitrile 14a (304.5 mg, 1.09 mmol) was dissolved during 1 h in
chilled concentrated sulfuric acid (20 mL). Then the mixture was
stirred at ꢀ10 to ꢀ5 ꢁC for next 2 h. The resulting solution was
poured onto crushed ice (ca. 120 g). The obtained suspension was
neutralized with aq NaOH, extracted with chloroform, dried over
anhydrous magnesium sulfate and the solvent was removed under
reduced pressure. Crude product was purified by column chroma-
tography (chloroform/SiO2) to give aminonitrile 15 (268.4 mg, yield
88.1%) as beige small crystals. An analytical sample of 15 was
obtained by recrystallization from ethanol. Mp 175–178 ꢁC. IR (KBr)
3471, 3385, 3244 (nN–H), 3082, 3050, 2924, 2853, 2201 (CN), 1645
9. (a) Piao, G.; Akagi, K.; Shirakawa, H.; Kyotani, M. Curr. Appl. Phys. 2001, 1, 121–
123; (b) Akagi, K.; Piao, G.; Kaneko, S.; Higuchi, I.; Shirakawa, H.; Kyotani, M.
Synth. Met. 1999, 102, 1406–1409.
10. Kozik, B.; Wilamowski, J.; Go´ra, M.; Sepio1, J. J. Tetrahedron Lett. 2006, 47, 3435–
3438.
11. Sepiol, J. J.; Wilamowski, J. Tetrahedron Lett. 2001, 42, 5287–5289.
´
12. Krasodomski, W.; quczynski, M. K.; Wilamowski, J.; Sepio1, J. J. Tetrahedron
2003, 59, 5677–5683.
(
dN–H), 1598, 1563, 1510, 1491, 1439, 1405, 1093, 1011, 890, 826, 778,
13. Sepiol, J. J.; Gora, M.; Luczynski, M. K. Synlett 2001, 1383–1386.
14. Aldehyde 4a and ketone 4b are commercially available from Fluka Chemie AG
and Aldrich-Chemical Co. Ltd, respectively.
15. Zimmerman, H. E.; Armesto, D.; Amezua, M. G.; Gannett, T. P.; Johnson, R. P. J.
Am. Chem. Soc. 1979, 101, 6367–6383.
16. (a) Kobayashi, K.; Uneda, T.; Takada, K.; Tanaka, H.; Kitamura, T.; Morikawa, O.;
Konishi, H. Chem. Lett. 1996, 25–26; (b) Kobayashi, K.; Uneda, T.; Takada, K.;
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2000, 41, 1527–1530.
762, 718, 682 cmꢀ1. 1H NMR (CDCl3)
d
5.15 (br s, 2H, NH2), 7.26 (s,
1H, C3–H), 7.31–7.35 (m, 2H, Ar–H), 7.43–7.46 (m, 2H, Ar–H), 7.54–
7.59 (m, 2H, C6–H, C7–H), 7.78–7.81 (m, 1H, C5–H or C8–H), 7.87–
7.89 (m, 1H, C8–H or C5–H). 13C NMR (CDCl3)
d 89.4 (C2), 118.4 (CN),
121.5, 122.1, 126.3, 126.7, 126.8, 128.7 (2ꢂCAr), 129.1, 129.8, 131.4
(2ꢂCAr), 133.5, 134.1, 137.8, 147.8 (C1). Anal. Calcd for C17H11ClN2: C,
73.25; H, 3.98; N, 10.05%. Found: C, 73.02; H, 3.77; N, 9.90%.
18. Amedio, J. C., Jr.; Bernard, P. J.; Fountain, M.; Van Wagenen, G., Jr. Synth. Com-
mun. 1998, 28, 3895–3906.
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382.
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980.
3.3.10. Cyclization of 3-(4-chlorophenyl)-2-methyl-3-phenylprop-
1-ene-1,1-dicarbonitrile (14b). 1-Amino-4-(4-chlorophenyl)-3-
methylnaphthalene-2-carbonitrile (16a) and 1-amino-6-chloro-3-
methyl-4-phenylnaphthalene-2-carbonitrile (16b)
21. (a) Stoermer, R. Ber. Dtsch. Chem. Ges. 1906, 39, 2288–2306; (b) Hatch, M. J.;
Cram, D. J. J. Am. Chem. Soc. 1953, 75, 38–44.
Dinitrile 14b (203.7 mg, 0.696 mmol) was dissolved in chilled
concentrated sulfuric acid (9 mL). The reaction progress was
monitored by TLC (toluene/SiO2). The mixture was stirred at ꢀ15 to
ꢀ10 ꢁC for 2 h. The resulting solution was poured onto crushed ice
22. (a) The chemical shifts and the coupling constants from simulated 1H
NMR spectrum of aminonitrile 3: 1H NMR
d 2.27 (s, 3H, C3–CH3), 2.34 (ddd, 3H,
4JMe–H5¼0.88 Hz, 4JMe–H7¼0.34 Hz, 5JMe–H8¼0.22 Hz, C6–CH3), 5.08 (br s, 2H, NH2),

6460
B. Kozik et al. / Tetrahedron 64 (2008) 6452–6460
4
4
5
7.09 (dqd, 1H, JH5–H7¼1.45 Hz, JH5–Me¼0.88 Hz, JH5–H8¼0.52 Hz, C5–H), 7.19
23. Sato, Y.; Yato, M.; Ohwada, T.; Saito, S.; Shudo, K. J. Am. Chem. Soc. 1995, 117,
(dddd, 2H, 3J¼7.61 Hz, 4J¼1.92 Hz, 4J¼1.29 Hz, J¼0.65 Hz, C20–H, C60–H), 7.28
3037–3043.
5
3
4
4
(ddq, 1H, JH7–H8¼8.60 Hz, JH7–H5¼1.45 Hz, JH7–Me¼0.34 Hz, C7–H), 7.43 (tt,
24. Grochowski, J.; Serda, P.; Markiewicz, M.; Kozik, B.; Sepiol, J. J. J. Mol. Struct.
4
1H, 3J¼7.48 Hz, J¼1.29 Hz, C40–H), 7.48 (dddd, 2H, 3J¼7.61 Hz, 3J¼7.48 Hz, 4J¼1.
2004, 689, 43–48.
5
3
5
37 Hz, J¼0.65 Hz, C30–H, C50–H), 7.70 (ddq, 1H, JH8–H7¼8.60 Hz, JH8–H5¼0.
25. Kozik, B.; Burgie1, Z. J.; Sepio1, J. J.; Wilamowski, J.; quczyn´ ski, M. K.; Go´ra, M.
5
52 Hz, JH8–Me¼0.22 Hz, C8–H); (b) Quirt, A. R.; Martin, J. S. J. Magn. Reson.
Env. Biotech. 2006, 2, 20–25 (available online at http://www.uwm.edu.pl/wosir/
EB/).
26. Wilamowski, J.; Kulig, E.; Sepiol, J. J.; Burgiel, Z. J. Pest Manag. Sci. 2001, 57, 625–
1971, 5, 318–327; (c) Marat, K. SpinWorks 2.5.5; University of Manitoba:
Winnipeg, Manitoba, Canada, 2006, http://www.umanitoba.ca/chemistry/nmr/
spinworks.
632.