Synthesis of 1-aminonaphthalene-2-carbonitrile derivatives by the reaction of 2-vinylbenzonitriles with 2-lithioacetonitrile

Article abstract of DOI:10.1055/s-2008-1032153

A new and simple method for the preparation of 1-aminonaphthalene-2- carbonitrile derivatives has been developed. When 2-(1-arylethenyl)benzonitriles are treated with 2-lithioacetonitrile, 1-amino-4-aryl-3,4-dihydronaphthalene-2- carbonitriles are obtained in good yields. The reaction of 2-(1-aryl-2- methoxyethenyl)benzonitriles with 2-lithioacetonitrile leads to the formation of 1-amino-4-arylnaphthalene-2-carbonitriles in fair-to-good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032153

584
PAPER
Synthesis of 1-Aminonaphthalene-2-carbonitrile Derivatives by the Reaction
of 2-Vinylbenzonitriles with 2-Lithioacetonitrile
S
ynthesis of 1-A
m
a
inonaphtha
z
lene-2-car
b
u
onitriles hiro Kobayashi,* Kenichi Hashimoto, Takahiro Ukon, Shuhei Fukamachi, Osamu Morikawa,
Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University, Koyama-minami, Tottori 680-8552, Japan
Fax +81(857)315263; E-mail: kkoba@chem.tottori-u.ac.jp
Received 3 October 2007; revised 8 November 2007
Ar
Ar
Abstract: A new and simple method for the preparation of 1-ami-
nonaphthalene-2-carbonitrile derivatives has been developed.
When 2-(1-arylethenyl)benzonitriles are treated with 2-lithioaceto-
nitrile, 1-amino-4-aryl-3,4-dihydronaphthalene-2-carbonitriles are
obtained in good yields. The reaction of 2-(1-aryl-2-methoxyethe-
nyl)benzonitriles with 2-lithioacetonitrile leads to the formation of
1-amino-4-arylnaphthalene-2-carbonitriles in fair-to-good yields.
R
R
LiCH2CN, THF
–78 to 0 °C
CN
CN
NH2
1
a Ar = Ph, R = H
2a 77%
2b 86%
2c 83%
2d 86%
2e 82%
2f 86%
b Ar = 3-MeC6H4, R = H
c Ar = 4-MeC6H4, R = H
d Ar = 4-MeOC6H4, R = H
e Ar = 1-naphthyl, R = H
Key words: arenes, carbanions, nitriles, ring closure, tandem reac-
tion
f
Ar = Ph, R = OMe
Scheme 1
In previous papers, we reported a new short-step general
synthesis of 4-aryl-3,4-dihydroisoquinoline derivatives
based on the reaction of 2-(1-arylethenyl)benzonitriles
with organolithiums.1 Subsequently, we decided to exam-
ine the reaction of 2-(1-arylethenyl)benzonitriles 1 with 2-
lithioacetonitrile, and found that it gave 1-amino-4-aryl-
3,4-dihydronaphthalene-2-carbonitriles 2. On the other
hand, it was noted that the reaction using 2-(1-aryl-2-
methoxyethenyl)benzonitriles 3 in place of 1 afforded
1-aminonaphthalene-2-carbonitriles 4. In this paper we
wish to describe the results of these studies. Compounds
having an enamino nitrile moiety have already proven to
be useful precursors for the synthesis of a variety of het-
erocycles,2 some of which have reported to be of biologi-
cal importance. However, only a few general synthetic
methods of 1-aminonaphthalene-2-carbonitrile deriva-
tives have been developed.3,4
As expected, subjecting 3 to the reaction with two molar
amounts of 2-lithioacetonitrile under the same conditions
as described for the preparation of 2 gave the desired
products 4, but the yields were somewhat lower than those
of 2, as illustrated in Scheme 2. When lithium enolates of
tert-butyl acetate and N,N-dimethylacetamide were used,
the starting nitrile was recovered almost quantitatively in
each case.
Ar
Ar
OMe
LiCH2CN, THF
–78 to 0 °C
CN
CN
NH2
3
a Ar = Ph
4a 66%
4b 65%
4c 74%
4d 71%
4e 66%
The preparation of 1-amino-4-aryl-3,4-dihydronaphtha-
lene-2-carbonitriles 2 was carried out as shown in
Scheme 1. Thus, treatment of 2-(1-arylethenyl)benzoni-
triles 1 with two molar amounts of 2-lithioacetonitrile,
generated by treatment of acetonitrile with butyllithium in
THF at –78 °C,5 at the same temperature followed by rais-
ing reaction temperature to 0 °C, resulted in the efficient
production of the desired products 2, after aqueous work-
up. Scheme 1 also shows the yields of the products, which
are generally good independent of the a-aryl substituents
and the 4-methoxy group of the starting nitriles 1.
b Ar = 3-MeC6H4
c Ar = 4-MeC6H4
d Ar = 4-MeOC6H4
e Ar = 1-naphthyl
Scheme 2
The mechanistic rationale, depicted in Scheme 3, begins
with coupling of the first molecule of 2-lithioacetonitrile
with the nitrile of 2-vinylbenzonitrile derivatives 1 and 3
to give the adduct 5. Abstraction of a hydrogen a to the ni-
trile of this adduct by the second molecule of 2-lithioace-
tonitrile gives the dianionic intermediate 6, which
undergoes an intramolecular ring closure to give the ben-
zylic anion intermediate 7. The intermediate 7 (X = H)
gives 2 through successive tautomerization via the inter-
mediate 8, and protonation (or in the inverse order). On
the other hand, the intermediate 8 (X = OMe) loses meth-
oxide after the tautomerization (or in the inverse order) to
It was envisioned that the use of 2-(1-aryl-2-methoxyethe-
nyl)benzonitriles 3 in the place of 1 would be capable of
affording 1-amino-4-arylnaphthalene-2-carbonitriles 4.
SYNTHESIS 2008, No. 4, pp 0584–0588
x
x
.
x
x
.2
0
0
8
Advanced online publication: 31.01.2008
DOI: 10.1055/s-2008-1032153; Art ID: F18107SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 1-Aminonaphthalene-2-carbonitriles
585
none,7 2-[1-(4-methoxyphenyl)ethenyl]benzonitrile (1d),8 and 2-
bromophenyl(1-naphthyl)methanone9 were prepared by reported
methods. All other chemicals used in this study were commercially
available.
provide 4 as the result of protonation. Although the possi-
bility of anion-promoted electrocyclic reaction of the en-
amido form of the intermediate 5 for the present ring
closure cannot be excluded, the mechanism depicted in
Scheme 3 may explain the necessity of two molar
amounts of 2-lithioacetonitrile for the satisfactory produc-
tion of the desired products 2 and 4. It is noteworthy that
no products arising from the addition of imino anion of the
adduct 5 to the b-carbon atom of the vinyl moiety were
isolated.
2-(2-Methoxy-1-phenylethenyl)benzonitrile (3a)10
To a stirred suspension of (methoxymethyl)triphenylphosphonium
chloride (3.4 g, 9.9 mmol) in 1,2-dimethoxyethane (DME, 70 mL)
at 0 °C under argon was added dropwise BuLi (1.6 M in hexane; 6.2
mL, 9.9 mmol). After 5 min, the resulting ylide was treated with a
solution of 2-benzoylbenzonitrile1,6 (1.6 g, 7.5 mmol) in DME (15
mL) and stirring was continued for an additional 10 min at the same
temperature. H2O (30 mL) was added and the mixture was extracted
with Et2O (2 × 30 mL). The combined extracts were washed with
H2O (20 mL) and brine (20 mL), dried (Na2SO4), and evaporated.
The residue was purified by column chromatography on silica gel
(hexane–Et2O, 2:1) to give 3a. Yield: 1.3 g (73%); yellow oil; mix-
ture of stereoisomers (E/Z = ~1:1); Rf = 0.36 (hexane–Et2O, 2:1).
Ar
R
X
LiCH2CN
1 or 3
CN
N
IR (neat): 2225, 1634 cm–1.
5
1H NMR (270 MHz): d = 3.82 and 3.84 (2 s, 3 H), 6.49 (s, 0.5 H),
6.69 (s, 0.5 H), 7.11 (dd, J = 7.9, 1.6 Hz, 1 H), 7.20–7.40 (m, 6 H),
7.45–7.60 (m, 1 H), 7.72 (d, J = 8.6 Hz, 0.5 H) and 7.76 (d, J = 7.9
Hz, 0.5 H).
Ar
Ar
N
R
X
C
R
X
LiCH2CN
CN
Anal. Calcd for C16H13NO: C, 81.68; H, 5.57; N, 5.95. Found: C,
81.46; H, 5.52; N, 5.90.
N
N
7
6
2-(3-Methylbenzoyl)benzonitrile
Ar
This compound was prepared from 2-bromo-4-methyl-
benzophenone7 and CuCN under the conditions reported by Fried-
man et al.11 Yield: 61%; white solid; mp 53–55 °C (hexane–
CH2Cl2). IR (KBr): 2228, 1663 cm–1.
R
X
H3O+
X = H
2
CN
NH
1H NMR (500 MHz): d = 2.43 (s, 3 H), 7.38 (t, J = 7.8 Hz, 1 H),
7.46 (d, J = 7.3 Hz, 1 H), 7.57 (d, J = 7.8 Hz, 1 H), 7.64–7.71 (m, 4
H), 7.85 (dd, J = 7.8, 1.4 Hz, 1 H).
8
X = OMe
H3O+
–
–OMe
Anal. Calcd for C15H11NO: C, 81.43; H, 5.01; N, 6.33. Found: C,
81.36; H, 5.15; N, 6.36.
4
2-[1-(3-Methylphenyl)ethenyl]benzonitrile (1b)
Scheme 3
This compound was prepared by treating 2-(3-methylbenzoyl)ben-
zonitrile with methylenetriphenylphosphorane under conditions for
the preparation of 1a reported by us.1 Yield: 64%; yellow oil;
Rf = 0.41 (THF–hexane, 1:10).
In conclusion, we have developed a new method for pre-
paring 1-aminonaphthalene-2-carbonitrile derivatives.
The present procedure may find some value in organic
synthesis, because it has some advantages over the previ-
ously reported methods; simple manipulations as well as
ready availability of the starting materials.
IR (neat): 2226, 1614, 1601 cm–1.
1H NMR (500 MHz): d = 2.33 (s, 3 H), 5.47 (s, 1 H), 5.86 (s, 1 H),
7.05 (d, J = 7.8 Hz, 1 H), 7.08 (s, 1 H), 7.13 (d, J = 7.8 Hz, 1 H),
7.22 (dd, J = 7.8, 7.3 Hz, 1 H), 7.36 (dd, J = 7.8, 0.9 Hz, 1 H), 7.42
(ddd, J = 7.8, 7.3, 0.9 Hz, 1 H), 7.57 (ddd, J = 7.8, 7.3, 0.9 Hz, 1 H),
7.71 (dd, J = 7.8, 0.9 Hz, 1 H).
All melting points were obtained on a Laboratory Devices MEL-
TEMP II melting apparatus and are uncorrected. IR spectra were re-
corded on a Shimadzu FTIR-8300 spectrophotometer. The 1H NMR
spectra were recorded in CDCl3 using TMS as an internal reference
using a JEOL ECP500 FT NMR spectrometer operating at 500
MHz or JEOL GX270 FT NMR spectrometer operating at 270
MHz. The 13C NMR spectra were recorded in CDCl3 using TMS as
an internal reference on a JEOL ECP500 FT NMR spectrometer op-
erating at 125 MHz. Low-resolution MS spectra (EI, 70 eV) were
measured using a JEOL AUTOMASS 20 spectrometer. TLC was
carried out on a Merck Kieselgel 60 PF254. Column chromatography
was performed using Merck Kieselgel 60 (0.063–0.200 mm). All of
the organic solvents used in this study were dried over appropriate
drying agents and distilled prior to use.
Anal. Calcd for C16H13N: C, 87.64; H, 5.98; N, 6.39. Found: C,
87.49; H, 6.11; N, 6.38.
2-[2-Methoxy-1-(3-methylphenyl)ethenyl]benzonitrile (3b)
This compound was prepared by treating 2-(3-methylbenzoyl)ben-
zonitrile with (methoxymethylene)triphenylphosphorane as de-
scribed for the preparation of 3a. Yield: 74%; mixture of
stereoisomers (E/Z = ~8:2); colorless oil; Rf = 0.44 (CH2Cl2–hex-
ane, 1:1).
IR (neat): 2226, 1637, 1601 cm–1.
1H NMR (500 MHz): d = 2.30 and 2.31 (2 s, 3 H), 3.82 (s, 2.4 H),
3.84 (s, 0.6 H), 6.48 (s, 0.2 H), 6.68 (s, 0.8 H), 6.91 (d, J = 7.8 Hz,
1 H), 6.93 (s, 1 H), 7.04 (d, J = 7.3 Hz, 0.8 H), 7.14 (d, J = 7.8 Hz,
0.2 H), 7.16 (dd, J = 7.8, 7.3 Hz, 0.8 H), 7.21 (dd, J = 7.8, 7.3 Hz,
0.2 H), 7.27 (dd, J = 7.8, 0.9 Hz, 0.8 H), 7.29 (dd, J = 7.8, 0.9 Hz,
2-(1-Phenylethenyl)benzonitrile (1a),1 2-benzoylbenzonitrile,1,6 2-
bromo-3-methylbenzophenone,7
2-bromo-4-methylbenzophe-
Synthesis 2008, No. 4, 584–588 © Thieme Stuttgart · New York

586
K. Kobayashi et al.
PAPER
0.2 H), 7.34 (td, J = 7.8, 0.9 Hz, 0.2 H), 7.36 (td, J = 7.8, 0.9 Hz, 0.8
H), 7.50 (td, J = 7.8, 1.4 Hz, 0.2 H), 7.55 (td, J = 7.8, 0.9 Hz, 0.8 H),
7.67 (dd, J = 7.8, 1.4 Hz, 0.2 H), 7.72 (dd, J = 7.8, 0.9 Hz, 0.8 H).
Anal. Calcd for C17H15NO2: C, 76.98; H, 5.70; N, 5.28. Found: C,
76.96; H, 5.99; N, 5.21.
2-(1-Naphthoyl)benzonitrile
Anal. Calcd for C17H15NO: C, 81.90; H, 6.06; N, 5.62. Found: C,
81.80; H, 6.08; N, 5.37.
This compound was prepared from 2-bromophenyl(1-naphth-
yl)methanone9 and CuCN under the conditions reported by Fried-
man et al.11 Yield: 40%; pale-yellow solid; mp 94–95 °C (hexane–
CH2Cl2).
2-(4-Methylbenzoyl)benzonitrile
This compound was prepared from 2-bromo-4-methyl-
benzophenone7 and CuCN under the conditions reported by Fried-
man et al.11 Yield: 48%; pale-yellow solid; mp 111–113 °C
(hexane–CH2Cl2).
IR (KBr): 2230, 1651 cm–1.
1H NMR (500 MHz): d = 7.50 (dd, J = 8.2, 7.3 Hz, 1 H), 7.57–7.69
(m, 6 H), 7.88 (dd, J = 8.2, 1.4 Hz, 1 H), 7.95 (dd, J = 7.8, 1.8 Hz,
1 H), 8.08 (d, J = 8.2 Hz, 1 H), 8.45 (dd, J = 7.8, 1.4 Hz, 1 H).
IR (KBr): 2228, 1661, 1601 cm–1.
1H NMR (500 MHz): d = 2.45 (s, 3 H), 7.30 (d, J = 8.2 Hz, 2 H),
7.63–7.69 (m, 3 H), 7.71 (d, J = 8.2 Hz, 2 H), 7.83 (dd, J = 7.8, 1.4
Hz, 1 H).
Anal. Calcd for C18H11NO: C, 84.03; H, 4.31; N, 5.44. Found: C,
84.01; H, 4.71; N, 5.28.
2-[1-(1-Naphthyl)ethenyl]benzonitrile (1e)
Anal. Calcd for C15H11NO: C, 81.43; H, 5.01; N, 6.33. Found: C,
81.38; H, 5.02; N, 6.21.
This compound was prepared by treating 2-(1-naphthoyl)benzoni-
trile with methylenetriphenylphosphorane under conditions for the
preparation of 1a reported by us.1 Yield: 57%; yellow viscous oil;
Rf = 0.52 (THF–hexane, 1:4).
2-[1-(4-Methylphenyl)ethenyl]benzonitrile (1c)
This compound was prepared by treating 2-(4-methylbenzoyl)ben-
zonitrile with methylenetriphenylphosphorane under conditions for
the preparation of 1a reported by us.1 Yield: 63%; yellow oil;
Rf = 0.50 (Et2O–hexane, 1:1).
IR (neat): 2224 cm–1.
1H NMR (500 MHz): d = 5.84 (s, 1 H), 6.12 (s, 1 H), 7.18 (d, J = 7.8
Hz, 1 H), 7.34 (ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.37–7.46 (m, 4 H),
7.49 (dd, J = 7.8, 7.3 Hz, 1 H), 7.74 (dd, J = 7.8, 1.4 Hz, 1 H), 7.80
(d, J = 8.7 Hz, 1 H), 7.87 (d, J = 8.2 Hz, 2 H).
IR (neat): 2226, 1615 cm–1.
1H NMR (500 MHz): d = 2.35 (s, 3 H), 5.42 (s, 1 H), 5.84 (s, 1 H),
7.13 (d, J = 8.2 Hz, 2 H), 7.15 (d, J = 8.2 Hz, 2 H), 7.36 (d, J = 7.8
Hz, 1 H), 7.41 (ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.56 (ddd, J = 7.8,
7.3, 1.4 Hz, 1 H), 7.70 (dd, J = 7.8, 1.4 Hz, 1 H).
Anal: Calcd for C19H13N: C, 89.38; H, 5.13; N, 5.49. Found: C,
89.58; H, 5.36; N, 5.20.
2-[2-Methoxy-1-(1-naphthyl)ethenyl]benzonitrile (3e)
Anal. Calcd for C16H13N: C, 87.64; H, 5.98; N, 6.39. Found: C,
87.60; H, 6.07; N, 6.18.
This compound was prepared by treating 2-(1-naphthoyl)benzoni-
trile with (methoxymethylene)triphenylphosphorane as described
for the preparation of 3a. Yield: 72%; mixture of stereoisomers
(~1:1); colorless viscous oil; Rf = 0.31 (THF–hexane, 1:4).
2-[2-Methoxy-1-(4-methylphenyl)ethenyl]benzonitrile (3c)
This compound was prepared by treating 2-(4-methylbenzoyl)ben-
zonitrile with (methoxymethylene)triphenylphosphorane as de-
scribed for the preparation of 3a. Yield: 74%; mixture of
stereoisomers (~1:1); colorless oil; Rf = 0.40 (Et2O–hexane, 1:1).
IR (neat): 2224, 1639 cm–1.
1H NMR (500 MHz): d = 3.77 (s, 1.5 H), 3.89 (s, 1.5 H), 6.55 (s, 0.5
H), 7.04 (dd, J = 8.2, 0.9 Hz, 0.5 H), 7.07 (s, 0.5 H), 7.10 (dd,
J = 7.8, 0.9 Hz, 0.5 H), 7.21–7.27 (m, 1 H), 7.32 (td, J = 7.8, 1.4 Hz,
0.5 H), 7.35–7.52 (m, 4.5 H), 7.68 (dd, J = 7.8, 1.4 Hz, 0.5 H), 7.72
(J = 7.8, 0.9 Hz, 0.5 H), 7.81–7.89 (m, 3 H).
IR (neat): 2224, 1634 cm–1.
1H NMR (500 MHz): d = 2.32 (s, 1.5 H), 2.33 (s, 1.5 H), 3.81 (s, 1.5
H), 3.83 (s, 1.5 H), 6.45 (s, 0.5 H), 6.65 (s, 0.5 H), 7.01 (d, J = 8.2
Hz, 1 H), 7.08 (d, J = 8.2 Hz, 1 H), 7.12 (d, J = 8.2 Hz, 1 H), 7.23
(d, J = 8.2 Hz, 1 H), 7.27 (d, J = 7.8 Hz, 0.5 H), 7.30 (d, J = 7.8 Hz,
0.5 H), 7.34 (ddd, J = 7.8, 7.3, 0.9 Hz, 0.5 H), 7.35 (ddd, J = 7.8,
7.3, 0.9 Hz, 0.5 H), 7.50 (ddd, J = 7.8, 7.3, 1.4 Hz, 0.5 H), 7.54 (ddd,
J = 7.8, 7.3, 1.4 Hz, 0.5 H), 7.66 (dd, J = 7.8, 0.9 Hz, 0.5 H), 7.70
(dd, J = 7.8, 0.9 Hz, 0.5 H).
Anal. Calcd for C20H15NO: C, 84.19; H, 5.30; N, 4.91. Found: C,
84.07; H, 5.51; N, 4.72.
2-Benzoyl-4-methoxybenzonitrile10
This compound was prepared from 2-bromo-5-methoxy-
benzophenone12 and CuCN under the conditions reported by Fried-
man et al.11 Yield: 40%; white solid; mp 130–131 °C (hexane–
THF). IR (KBr): 2226, 1665 cm–1.
1H NMR (270 MHz): d = 3.89 (s, 3 H), 7.05–7.15 (m, 2 H), 7.50
(dd, J = 7.9, 7.3 Hz, 2 H), 7.65 (tt, J = 7.3, 1.3 Hz, 1 H), 7.74 (d,
J = 9.2 Hz, 1 H), 7.83 (dd, J = 7.9, 1.3 Hz, 2 H).
Anal. Calcd for C17H15NO: C, 81.90; H, 6.06; N, 5.62. Found: C,
81.87; H, 6.45; N, 5.57.
2-[2-Methoxy-1-(4-methoxyphenyl)ethenyl]benzonitrile (3d)
This compound was prepared by treating 2-(4-methoxyben-
zoyl)benzonitrile8 with (methoxymethylene)triphenylphosphorane
as described for the preparation of 3a. Yield: 54%; mixture of ste-
reoisomers (E/Z = ~6:4); pale-yellow oil; Rf = 0.45 (CH2Cl2–hex-
ane, 2:1).
Anal. Calcd for C15H11NO2: C, 75.94; H, 4.67; N, 5.90. Found: C,
76.04; H, 4.65; N, 5.84.
4-Methoxy-2-(1-phenylethenyl)benzonitrile (1f)
IR (KBr): 2226, 1634, 1607 cm–1.
This compound was prepared by treating 4-methoxy-2-
benzoylbenzonitrile10 with methylenetriphenylphosphorane under
conditions for the preparation of 1a reported by us.1 Yield: 53%;
yellow oil; Rf = 0.43 (THF–hexane, 1:4).
1H NMR (500 MHz): d = 3.79 and 3.80 (2 s, 4.8 H), 3.83 (s, 1.2 H),
6.41 (s, 0.4 H), 6.59 (s, 0.6 H), 6.81 (d, J = 8.7 Hz, 1.2 H), 6.85 (d,
J = 8.7 Hz, 0.8 H), 7.04 (d, J = 8.7 Hz, 1.2 H), 7.26–7.37 (m, 2.8 H),
7.51 (ddd, J = 7.8, 7.3, 1.4 Hz, 0.4 H), 7.54 (ddd, J = 7.8, 7.3, 1.4
Hz, 0.6 H), 7.66 (d, J = 7.8 Hz, 0.4 H), 7.70 (dd, J = 7.8, 0.9 Hz, 0.6
H).
IR (neat): 2222 cm–1.
1H NMR (500 MHz): d = 3.84 (s, 3 H), 5.48 (s, 1 H), 5.86 (s, 1 H),
6.84 (d, J = 2.3 Hz, 1 H), 6.92 (dd, J = 8.7, 2.3 Hz, 1 H), 7.27–7.35
(m, 5 H), 7.63 (d, J = 8.7 Hz, 1 H).
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PAPER
Synthesis of 1-Aminonaphthalene-2-carbonitriles
587
Anal. Calcd for C16H13NO: C, 81.68; H, 5.57; N, 5.95. Found: C,
81.54; H, 5.51; N, 5.75.
1-Amino-4-(1-naphthyl)-3,4-dihydronaphthalene-2-carbo-
nitrile (2e)
Pale-yellow solid; mp 181–182 °C (hexane–CH2Cl2).
1-Amino-4-phenyl-3,4-dihydronaphthalene-2-carbonitrile(2a);
Typical Procedure
IR (KBr): 3464, 3356, 3258, 2174, 1655, 1647, 1604 cm–1.
1H NMR (500 MHz): d = 2.85 (dd, J = 15.3, 6.7 Hz, 1 H), 2.96 (dd,
J = 15.3, 8.6 Hz, 1 H), 4.71 (br s, 2 H), 4.97 (dd, J = 8.6, 6.7 Hz, 1
H), 6.89 (d, J = 7.3 Hz, 1 H), 7.03 (d, J = 7.3 Hz, 1 H), 7.25–7.38
(m, 3 H), 7.50–7.53 (m, 3 H), 7.78 (d, J = 8.6 Hz, 1 H), 7.91–8.03
(m, 2 H).
13C NMR (125 MHz): d = 29.78, 39.89, 75.08, 120.37, 121.99,
123.43, 125.40, 125.60, 126.16 (2 C), 127.24, 127.72, 129.04,
129.24, 129.50, 130.64, 131.41, 134.19, 137.51, 140.57, 151.59
To a stirred solution of MeCN (0.21 g, 5.2 mmol) in THF (10 mL)
at –78 °C was added n-BuLi (1.6 M in hexane; 3.3 mL, 5.3 mmol).
After 15 min, a solution of 1a (0.54 g, 2.6 mmol) in THF (5 mL) was
added and the temperature was gradually raised to 0 °C. The result-
ing mixture was quenched with sat. aq NH4Cl (15 mL) and extracted
with Et2O (3 × 15 mL). The combined extracts were washed with
brine (15 mL), dried (Na2SO4), and evaporated. The residue was
subjected to column chromatography on silica gel to give 2a. Yield:
0.50 g (77%); light-gray solid; mp 182–184 °C (hexane–CH2Cl2).
MS: m/z (%) = 296 (100, [M+]).
IR (KBr): 3456, 3354, 3238, 2174, 1661, 1649 cm–1.
Anal. Calcd for C21H16N2: C, 85.11; H, 5.44; N, 9.45. Found; C,
85.05; H, 5.46; N, 9.38.
1H NMR (500 MHz): d = 2.74 (d, J = 7.8 Hz, 2 H), 4.13 (t, J = 7.8
Hz, 1 H), 4.65 (br s, 2 H), 6.96 (d, J = 7.3 Hz, 1 H), 7.15 (dd, J = 7.3,
1.4 Hz, 2 H), 7.25–7.36 (m, 5 H), 7.46 (dd, J = 7.8, 1.4 Hz, 1 H).
13C NMR (125 MHz): d = 30.60, 43.94, 74.69, 120.39, 122.01,
126.97, 127.17, 128.31, 128.62, 128.75, 129.08, 130.46, 140.76,
142.12, 151.61.
1-Amino-6-methoxy-4-phenyl-3,4-dihydronaphthalene-2-
carbonitrile (2f)
Pale-yellow solid; mp 115–117 °C (hexane–CH2Cl2).
IR (KBr): 3449, 3337, 3256, 2170, 1647, 1609 cm–1.
1H NMR (500 MHz): d = 2.70 (dd, J = 15.1, 7.8 Hz, 1 H), 2.72 (dd,
15.1, 7.3 Hz, 1 H), 3.73 (s, 3 H), 4.07 (dd, J = 7.8, 7.3 Hz, 1 H), 4.58
(br s, 2 H), 6.48 (dd, J = 2.7, 0.9 Hz, 1 H), 6.83 (dd, J = 8.7, 2.7 Hz,
1 H), 7.14 (dd, J = 7.3, 1.4 Hz, 2 H), 7.26 (tt, J = 7.3, 1.4 Hz, 1 H),
7.31 (t, J = 7.3 Hz, 2 H), 7.40 (d, J = 8.7 Hz, 1 H).
MS: m/z (%) = 246 (100, [M+]).
Anal. Calcd for C17H14N2: C, 82.90; H, 5.73; N, 11.37. Found; C,
82.81; H, 5.77; N, 11.34.
1-Amino-4-(3-methylphenyl)-3,4-dihydronaphthalene-2-carbo-
nitrile (2b)
Pale-yellow solid; mp 108–110 °C (hexane–Et2O).
IR (KBr): 3441, 3346, 3258, 2181, 1662, 1645, 1605 cm–1.
MS: m/z (%) = 276 (100, [M+]).
Anal. Calcd for C18H16N2O: C, 78.24; H, 5.84; N, 10.14. Found; C,
78.02; H, 5.86; N, 9.91.
1H NMR (500 MHz): d = 2.33 (s, 3 H), 2.71 (dd, J = 15.1, 7.3 Hz, 1
H), 2.73 (dd, J = 15.1, 8.7 Hz, 1 H), 4.09 (dd, J = 8.7, 7.3 Hz, 1 H),
4.65 (br s, 2 H), 6.92 (d, J = 7.8 Hz, 1 H), 6.94 (dd, J = 7.3, 1.4 Hz,
1 H), 6.97 (s, 1 H), 7.08 (d, J = 7.3 Hz, 1 H), 7.20 (dd, J = 7.8, 7.3
Hz, 1 H), 7.28–7.34 (m, 2 H), 7.45 (dd, J = 7.3, 1.8 Hz, 1 H).
1-Amino-4-phenylnaphthalene-2-carbonitrile (4a)
Pale-yellow solid; mp 95–97 °C (hexane–Et2O).
IR (KBr): 3474, 3377, 3254, 2206, 1634 cm–1.
1H NMR (500 MHz): d = 5.13 (br s, 2 H), 7.30 (s, 1 H), 7.40–7.44
(m, 3 H), 7.46–7.49 (m, 2 H), 7.53–7.59 (m, 2 H), 7.86–7.89 (m, 2
H).
MS: m/z (%) = 260 (100, [M+]).
Anal. Calcd for C18H16N2: C, 83.04; H, 6.19; N, 10.76. Found; C,
82.97; H, 6.18; N, 10.53.
MS: m/z (%) = 244 (100, [M+]).
Anal. Calcd for C17H12N2: C, 83.58; H, 4.95; N, 11.47. Found; C,
83.54; H, 4.96; N, 11.25.
1-Amino-4-(4-methylphenyl)-3,4-dihydronaphthalene-2-carbo-
nitrile (2c)
Light-gray solid; mp 111–112 °C (hexane–CH2Cl2).
IR (KBr): 3460, 3364, 3260, 2181, 1633 cm–1.
1-Amino-4-(3-methylphenyl)naphthalene-2-carbonitrile (4b)
Pale-yellow solid; mp 157–158 °C (hexane–CH2Cl2).
1H NMR (500 MHz): d = 2.34 (s, 3 H), 2.72 (d, J = 7.8 Hz, 2 H),
4.09 (t, J = 7.8 Hz, 1 H), 4.64 (br s, 2 H), 6.96 (dd, J = 7.3, 0.9 Hz,
1 H), 7.03 (d, J = 8.2 Hz, 2 H), 7.12 (d, J = 8.2 Hz, 2 H), 7.28–7.34
(m, 2 H), 7.45 (dd, J = 7.8, 1.4 Hz, 1 H).
IR (KBr): 3474, 3377, 3254, 2206, 1641 cm–1.
1H NMR (500 MHz): d = 2.43 (s, 3 H), 5.11 (br s, 2 H), 7.20–7.24
(m, 4 H), 7.28 (s, 1 H), 7.53–7.58 (m, 2 H), 7.86–7.90 (m, 2 H).
13C NMR (125 MHz): d = 21.46, 89.43, 118.58, 121.32, 122.08,
126.15, 126.50, 127.18, 127.27, 128.11, 128.26, 128.85, 130.78,
131.38, 134.29, 138.09, 139.25, 147.49.
MS: m/z (%) = 260 (100, [M+]).
Anal. Calcd for C18H16N2: C, 83.04; H, 6.19; N, 10.76. Found; C,
83.02; H, 6.22; N, 10.65.
MS: m/z (%) = 258 (100, [M+]).
Anal. Calcd for C18H14N2: C, 83.69; H, 5.46; N, 10.84. Found; C,
83.64; H, 5.49; N, 10.60.
1-Amino-4-(4-methoxphenyl)-3,4-dihydronaphthalene-2-
carbonitrile (2d)
Yellow solid; mp 173–176 °C (hexane–Et2O–CH2Cl2).
IR (KBr): 3439, 3342, 3258, 2181, 1660, 1645, 1615 cm–1.
1H NMR (500 MHz): d = 2.70 (d, J = 7.8 Hz, 2 H), 3.80 (s, 3 H),
4.08 (t, J = 7.8 Hz, 1 H), 4.64 (br s, 2 H), 6.86 (d, J = 8.7 Hz, 2 H),
6.96 (dd, J = 7.3, 1.4 Hz, 1 H), 7.06 (d, J = 8.7 Hz, 2 H), 7.28–7.34
(m, 2 H), 7.45 (dd, J = 7.8, 1.4 Hz, 1 H).
1-Amino-4-(4-methylphenyl)naphthalene-2-carbonitrile (4c)
Pale-yellow solid; mp 130–132 °C (hexane–Et2O).
IR (KBr): 3443, 3319, 3233, 2208, 1651 cm–1.
1H NMR (500 MHz): d = 2.44 (s, 3 H), 5.10 (br s, 2 H), 7.277 (s, 1
H), 7.284 (d, J = 8.2 Hz, 2 H), 7.30 (d, J = 8.2 Hz, 2 H), 7.52–7.58
(m, 2 H), 7.87–7.90 (m, 2 H).
MS: m/z (%) = 276 (100, [M+]).
MS: m/z (%) = 258 (100, [M+]).
Anal. Calcd for C18H16N2O: C, 78.24; H, 5.84; N, 10.14. Found; C,
78.15; H, 6.05; N, 9.93.
Synthesis 2008, No. 4, 584–588 © Thieme Stuttgart · New York

588
K. Kobayashi et al.
PAPER
Anal. Calcd for C18H14N2: C, 83.69; H, 5.46; N, 10.84. Found; C,
83.39; H, 5.60; N, 10.70.
Rodoríguez, T.; Torroba, T. Eur. J. Org. Chem. 2005, 5055.
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Heterocycles 2006, 67, 489. (k) Li, J.-R.; Ma, S.-L.; Sun,
Y.-J.; Wei, X.-J.; Zhou, Z. M. J. Heterocycl. Chem. 2006,
43, 745. (l) Jung, F. H.; Pasquet, G.; Lambert-van der
Brempt, C.; Lohmann, J.-J. M.; Warin, N.; Renaud, F.;
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Dousson, C.; Hill, G. B.; Mortlock, A. A.; Heron, N.;
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(r) Ji, Z.; Ahmed, A. A.; Albert, D. H.; Bouska, J. J.;
Bousquet, P. F.; Cunha, G. A.; Glaser, K. B.; Guo, J.; Li, J.;
Marcotte, P. A.; Moskey, M. D.; Pease, L. J.; Stewart, K. D.;
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1-Amino-4-(4-methoxyphenyl)naphthalene-2-carbonitrile (4d)
Yellow solid; mp 195–198 °C (hexane–Et2O–CH2Cl2).
IR (KBr): 3466, 3379, 3246, 2201, 1636, 1604 cm–1.
1H NMR (500 MHz): d = 3.89 (s, 3 H), 5.10 (br s, 2 H), 7.01 (d,
J = 8.7 Hz, 2 H), 7.27 (s, 1 H), 7.33 (d, J = 8.7 Hz, 2 H), 7.53–7.57
(m, 2 H), 7.86–7.89 (m, 2 H).
MS: m/z (%) = 274 (100, [M+]).
Anal. Calcd for C18H14N2O: C, 78.81; H, 5.14; N, 10.21. Found; C,
78.76; H, 5.03; N, 10.11.
1-Amino-4-(1-naphthyl)naphthalene-2-carbonitrile (4e)
Pale-yellow solid; mp 165–167 °C (dec.) (hexane–CH2Cl2).
IR (KBr): 3476, 3375, 3260, 2210, 1645 cm–1.
1H NMR (500 MHz): d = 5.20 (br s, 2 H), 7.29–7.59 (m, 9 H), 7.91–
7.96 (m, 3 H).
MS: m/z (%) = 294 (100, [M+]).
Anal. Calcd for C21H14N2: C, 85.69; H, 4.79; N, 9.52. Found; C,
85.67; H, 4.67; N, 9.46.
Acknowledgment
We thank Mrs. Miyuki Tanmatsu of this faculty for determining the
mass spectra and performing combustion analyses.
References
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Synthesis 2008, No. 4, 584–588 © Thieme Stuttgart · New York