Metal-free one-pot conversion of electron-rich aromatics into aromatic nitriles

Article abstract of DOI:10.1055/s-0029-1219575

Various electron-rich aromatics could be smoothly converted into the corresponding aromatic nitriles in good to moderate yields by treatment of electron-rich aromatics with POCl₃ and DMF, followed by treatment with molecular iodine in aqueous ammonia. The present reaction is a novel metal-free one-pot method for the preparation of aromatic nitriles from electron-rich aromatics.

Full text of DOI:10.1055/s-0029-1219575

LETTER
1067
Metal-Free One-Pot Conversion of Electron-Rich Aromatics into Aromatic
Nitriles
C
onversionof
o
Electron-Ric
u
hAromatics
s
intoArom
u
atic
N
itrile
s
ke Ushijima, Hideo Togo*
Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
Fax +81(43)2902792; E-mail: togo@faculty.chiba-u.jp
Received 18 January 2010
direct conversion of aromatic bromides into the corre-
Abstract: Various electron-rich aromatics could be smoothly con-
verted into the corresponding aromatic nitriles in good to moderate
yields by treatment of electron-rich aromatics with POCl3 and
DMF, followed by treatment with molecular iodine in aqueous am-
sponding aromatic nitriles, i.e., cyanodehalogenation, has
been actively studied with CuCN at DMF refluxing tem-
perature (the Rosenmund–von Braun reaction),5a
monia. The present reaction is a novel metal-free one-pot method Pd(OAc)2·K4[Fe(CN)6] at 120 °C,5b Pd·(binaphthyl)P
(t-Bu)2·Zn(CN)2·Zn at 80–95 °C,5c Pd2(dba)3·Zn(CN)2·
for the preparation of aromatic nitriles from electron-rich aromatics.
DPPF at 80–120 °C,5d Pd(tmhd)2·K4[Fe(CN)6] at 80 °C,5e
Key words: aromatics, aromatic N,N-dimethyliminium salt, aro-
Zn(CN)2·Pd2(dba)3 at 100 °C,5f Pd/C·CuI·K4[Fe(CN)6]
matic nitrile, Vilsmeier–Haack reaction, molecular iodine, aqueous
·3H2O at 130–140 °C,5g CuI·alkylimidazole·Pd/C·CuI
ammonia
·K4[Fe(CN)6] at 140–180 °C,5h Zn(CN)2·Pd2(dba)3· dppf
·Zn·ZnBr2 at 95 °C,5i and CuO·Pd·K4[Fe(CN)6] at 120 °C,5j
Aromatic nitriles are one of the most important synthetic all of which require toxic metal cyanides. More recently,
transformation precursors because they can be easily con- the direct and catalytic cyanation of aromatics containing
verted into esters, amides, carboxylic acids, amines, and 2-pyridyl group via C–H bond cleavage with
nitrogen-containing heterocycles, and aromatic nitriles Cu(OAc)2·TMSCN6a and Pd(OAc)2·CuBr·CuCN6b at 130
are also used as synthetic intermediates for agricultural °C, which requires toxic metal cyanides again, was report-
chemicals, pharmaceuticals, and functional materials.1 ed. Thus, an environmentally benign and economical ap-
Moreover, Citalopram hydrobromide® (treatment of alco- proach to convert aromatics into aromatic nitriles is in
hol dependency), Periciazine® (antipsychotic drug), great demand. To the best of our knowledge, studies on
Fadrozole® (oncolytic drug), and Letrozole® (breast can- the one-pot conversion of aromatics into the correspond-
cer therapy) are pharmaceutically important aromatic ni- ing aromatic nitriles using less toxic reagents are extreme-
triles.2 The most typical methods for the preparation of ly limited. One typical method is the reaction of aromatics
aromatic nitriles are the dehydration of aromatic amides with chlorosulfonyl isocyanate to form N-chlorosulfonyl
with SOCl2, TsCl–Py, P2O5, POCl3, COCl2, (EtO)3P–I2, or amides and the subsequent treatment with DMF to pro-
Ph3P–CCl4, the condensation of carboxylic acids with vide aromatic nitriles, together with the evolution of SO3
NH3–silica gel or NH3–ethyl polyphosphate, the reaction and HCl.7 On the other hand, molecular iodine is one of
of esters with Me2AlNH2,3 and the Sandmeyer reaction of the simplest oxidants currently available. It is highly af-
aromatic diazonium ion with toxic CuCN.3,4 On the other fordable and has very low toxicity. Considered to be an
hand, the preparation of aromatic nitriles from aromatics environmentally benign oxidizing agent for organic syn-
generally requires many steps as follows. The first typical thesis, molecular iodine is used in various organic reac-
preparation method of aromatic nitriles from aromatics is tions, including the oxidation of alcohols or aldehydes to
the halogenation of aromatics to give the aromatic halides, esters, the oxidation of sulfides to sulfoxides, the oxida-
the formation of the Grignard reagents with the aromatic tion of cyclohexenones to benzene rings, the introduction
halides, treatment of the Grignard reagents with CO2, the of protecting groups, the deprotection of protecting
formation of aroyl halides by reacting aromatic carboxylic groups, iodocyclization, carbon–carbon bond formation,
acids with thionyl chloride, treatment of the aroyl halides and the formation of heterocycles.8
with aqueous ammonia, and finally the dehydration of ar-
Here, as part of our ongoing studies on the use of molec-
omatic amides to provide aromatic nitriles. The second
ular iodine for organic synthesis,9 we would like to report
typical preparation method of aromatic nitriles from aro-
the one-pot conversion of aromatics into the correspond-
matics is the nitration of aromatics, the reduction of the ni-
ing aromatic nitriles. Recently, we have reported the di-
tro group to the amino group, treatment of aromatic
rect, efficient, practical, and less toxic oxidative
amines with NaNO2 and hydrochloric acid, and the reac-
conversion of benzylic halides into the corresponding ni-
tion of aromatic diazonium chlorides with CuCN to give
triles using molecular iodine in aqueous ammonia.9h,i
aromatic nitriles (the Sandmeyer reaction). Recently, the
Moreover, aldehydes could be smoothly converted into
the corresponding nitriles with molecular iodine in aque-
ous ammonia.9b,g,10 Thus, we planned to perform the met-
al-free one-pot conversion of aromatics into aromatic
nitriles using molecular iodine in aqueous ammonia. The
SYNLETT 2010, No. 7, pp 1067–1070
Advanced online publication: 10.03.2010
DOI: 10.1055/s-0029-1219575; Art ID: U00410ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
1
0

1068
S. Ushijima, H. Togo
LETTER
reaction was carried out as follows:11 To a flask contain-
ing aromatics were added POCl3 and DMF at 0 °C. Then,
the mixture was warmed at room temperature, 40 °C, 80
°C, or 100 °C, depending on the substrate for a few hours.
Then, molecular iodine and aqueous ammonia (28–30%)
were added to the reaction mixture and the obtained mix-
ture was stirred for three hours at room temperature to
provide the corresponding aromatic nitrile. The results are
Table 1 One-Pot Conversion of Aromatics into Aromatic Nitriles
through Aromatic N,N-Dimethyliminium Chlorides (continued)
POCl3 (1.1 equiv)
DMF (4.0 equiv)
+
Cl–
Ar–H
Ar–CH=N(CH3)2
temp., time
(6 mmol)
I2 (2.0 equiv)
Ar–CN
aq NH3 (12 mL)
r.t., 3 h
shown in Table 1. 1,3-Dimethoxybenzene, 1,3,5-tri- Entry Ar–H
methoxybenzene, indole, N-methylindole, 1-methoxy-
Temp
80 °C
Time Yield of nitrile
(%)a
naphthalene, 2-methoxynaphthalene, 1,5-dimethoxy-
naphthalene, and N,N-dimethylaniline gave the corre-
OMe
sponding aromatic nitriles as a single isomer in good
yields (entries 1, 2, 4–8, and 10).
8
9
4 h
91
OMe
Table 1 One-Pot Conversion of Aromatics into Aromatic Nitriles
through Aromatic N,N-Dimethyliminium Chlorides
100 °C
10 h
67
86
POCl3 (1.1 equiv)
DMF (4.0 equiv)
+
Cl–
Ar–H
Ar–CH=N(CH3)2
temp., time
(6 mmol)
I
2 (2.0 equiv)
10
11
80 °C
40 °C
2 h
1 h
Me2N
N
Ar–CN
aq NH3 (12 mL)
r.t., 3 h
87
(a/b = 72:25)
Entry Ar–H
Temp
Time Yield of nitrile
(%)a
Bn
12
13
80 °C
4 h
3 h
45
13
1
40 °C
3 h
3 h
74
99
S
OMe
OMe
MeO
100 °C
S
Br
2
40 °C
100 °C
r.t.
14
15
80 °C
80 °C
2 h
2 h
76
91
OMe
OMe
MeO
S
C10H21
MeO
3
4 h
3 h
59
81
O
C10H21
MeO
16
17
100 °C
100 °C
6 h
6 h
12
0
4
O
S
N
H
5
40 °C
3 h
99
N
a Isolated yield.
Me
The same treatment of 1,2,3-trimethoxybenzene, an-
thracene, and thiophene provided the corresponding aro-
matic nitriles in moderate yields (entries 3, 9 and 12),
although the treatment of 2-bromothiophene gave 5-cy-
ano-2-bromothiophene in low yield (entry 13). N-Ben-
zylpyrrole gave a 75:25 mixture of 2-cyano- and 3-cyano-
N-benzylpyrroles in good yield (entry 11). On the other
hand, the same treatment of 2-decylthiophene and 2-de-
cylfuran gave the corresponding heteroaromatic nitriles as
a single isomer in good yields (entries 14 and 15). Where-
as, 3-cyanobenzofuran was obtained in low yield by the
same treatment of benzofuran (entry 16), 3-cyanoben-
zothiophene was not obtained at all even at 100 °C in the
6
7
100 °C
100 °C
2 h
6 h
99
90
OMe
OMe
Synlett 2010, No. 7, 1067–1070 © Thieme Stuttgart · New York

LETTER
Conversion of Electron-Rich Aromatics into Aromatic Nitriles
1069
first step (entry 17). The reason is as follows: the initial
formation of aromatic N,N-dimethyliminium chloride by
the reaction of benzothiophene with POCl3 and DMF did
not occur at all, because the electron density on the aro-
matics was not sufficiently high. Moreover, 1-cyanonaph-
thalene, 4-cyanobiphenyl, and 2,5-dimethoxybenzonitrile
were not formed at all by the present method with naph-
thalene, biphenyl, and 1,4-dimethoxybenzene, respective-
ly, even at 100 °C in the first step. Practically, the
Vilsmeier–Haack reaction of benzothiophene, naphtha-
lene, biphenyl, and 1,4-dimethoxybenzene did not occur
at all.
Acknowledgment
Financial support in the form of a Grant-in-Aid for Scientific Rese-
arch (No. 20550033) from the Ministry of Education, Culture,
Sports, Science, and Technology in Japan, the Iodine Research Pro-
ject in Chiba University, and the Futaba Electronics Memorial
Foundation is gratefully acknowledged.
References and Notes
(1) Fabiani, M. E. Drug News Perspect. 1999, 12, 207.
(2) (a) Friedrick, K.; Wallensfels, K. The Chemistry of the
Cyano Group; Rappoport, Z., Ed.; Wiley Interscience: New
York, 1970. (b) North, M. Comprehensive Organic
Functional Group Transformation; Katritzky, A. R.; Meth-
Cohn, O.; Rees, C. W., Eds.; Pergamon: Oxford, 1995.
(c) Murahashi, S.-I. Synthesis from Nitriles with Retention of
the Cyano Group, In Science of Synthesis, Vol. 19; Georg
Thieme Verlag: Stuttgart, 2004, 345–402. (d) Collier, S. J.;
Langer, P. Application of Nitriles as Reagents for Organic
Synthesis with Loss of the Nitrile Functionality, In Science of
Synthesis, Vol. 19; Georg Thieme Verlag: Stuttgart, 2004,
403–425.
The plausible reaction mechanism is shown in Scheme 1.
The initial step involves the Vilsmeier–Haack reaction to
form aromatic N,N-dimethyliminium salt I. Once the aro-
matic N,N-dimethyliminium salt I is formed, it reacts
smoothly with ammonia to form the corresponding aro-
matic imine II, which further reacts with molecular iodine
to generate the corresponding aromatic N-iodoimine III.
The elimination of HI from aromatic N-iodoimine III rap-
idly occurs in aqueous ammonia to provide the corre-
sponding aromatic nitrile.9
(3) Comprehensive Organic Transformations; Larock, R. C.,
Ed.; Wiley-VCH: Weinheim, 1989, 976–993.
(4) Sandmeyer, T. Ber. 1884, 17, 2650.
(5) (a) Sharman, W. M.; Van Lier, J. E. in Porphyrin
Handbook, Vol. 15; Kadish, E.; Smith, K. M.; Guilard, R.,
Eds.; Academic Press: New York, 2003, 1. (b) Weissman,
S. A.; Zewge, D.; Chen, C. J. Org. Chem. 2005, 70, 1508.
(c) Littke, A.; Soumeillant, M.; Kaltenbach, R. F. III.;
Cherney, R. J.; Tarby, C. M.; Kiau, S. Org. Lett. 2007, 9,
1711. (d) Martin, M. T.; Liu, B.; Cooley, B. E. Jr.; Eaddy,
J. F. Tetrahedron Lett. 2007, 48, 2555. (e) Nandurkar, N.
S.; Bhanage, B. M. Tetrahedron 2008, 64, 3655. (f) Iqbal,
Z.; Lyubimtsev, A.; Hanack, M. Synlett 2008, 2287.
(g) Chen, G.; Weng, J.; Zheng, Z.; Zhu, X.; Cai, Y.; Cai, J.;
Wan, Y. Eur. J. Org. Chem. 2008, 3524. (h) Schareina, T.;
Zapf, A.; Cotte, A.; Müller, N.; Beller, M. Synthesis 2008,
3351. (i) Buono, F. G.; Chidambaram, R.; Mueller, R. H.;
Waltermire, R. E. Org. Lett. 2008, 10, 5325.
1) POCl3, DMF, warm
2) I2, aq NH3, r.t.
Ar
H
Ar
C
N
+
2 Cl–
Ar CH=NMe
– HI
I
NH3 – HNMe2
I
I2
Ar CH
NH
Ar
C
N
– HI
II
H
III
(j) Chattopadhyay, K.; Dey, R.; Ranu, B. C. Tetrahedron
Lett. 2009, 50, 3164.
Scheme 1 Possible reaction pathway for nitrile
(6) (a) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am.
Chem. Soc. 2006, 128, 6790. (b) Jia, X.; Yang, D.; Zhang,
S.; Cheng, J. Org. Lett. 2009, 11, 4716.
(7) (a) Gerhard, L. Ber. 1967, 100, 2719. (b) Gerhard, L. Org.
Synth. 1970, 50, 52.
In conclusion, various electron-rich aromatics, such as
1,3-dimethoxybenzene, 1,3,5-trimethoxybenzene, 1-
methoxynaphthalene,
2-methoxynaphthalene,
1,5-
(8) Reviews: (a) Togo, H.; Iida, S. Synlett 2006, 2159.
(b) Togo, H. J. Synth. Org. Chem. 2008, 66, 652.
(9) (a) Mori, N.; Togo, H. Synlett 2004, 880. (b) Mori, N.;
Togo, H. Synlett 2005, 1456. (c) Mori, N.; Togo, H.
Tetrahedron 2005, 61, 5915. (d) Ishihara, M.; Togo, H.
Synlett 2006, 227. (e) Iida, S.; Togo, H. Synlett 2006, 2633.
(f) Ishihara, M.; Togo, H. Tetrahedron 2007, 63, 1474.
(g) Iida, S.; Togo, H. Tetrahedron 2007, 63, 8274. (h) Iida,
S.; Togo, H. Synlett 2008, 1639. (i) Iida, S.; Ohmura, R.;
Togo, H. Tetrahedron 2009, 65, 6257.
(10) (a) Misono, A.; Osa, T.; Koda, S. Bull. Chem. Soc. Jpn.
1966, 39, 854. (b) Talukdar, S.; Hsu, J.; Chou, T.; Fang, J.
Tetrahedron Lett. 2001, 42, 1103.
(11) Typical Experimental Procedure: To a flask containing
1,3,5-trimethoxybenzene (1009.1 mg, 6 mmol) were added
POCl3 (1011.9 mg, 6.6 mmol) and DMF (1754.1 mg, 24
mmol) at 0 °C. After being stirred for 3 h at 40 °C, I2 (3045.7
mg, 12 mmol) and aq ammonia (12 mL, 28–30%) were
added to the reaction mixture. The obtained mixture was
dimethoxynaphthalene, aniline, indole, thiophene, furan,
and pyrrole, could be smoothly converted into the corre-
sponding aromatic nitriles in good yields, by treatment
with POCl3 and DMF, followed by the reaction with mo-
lecular iodine in aqueous ammonia. The present reaction
is a novel metal-free one-pot conversion of aromatics into
the corresponding aromatic nitriles, although the reaction
is limited to electron-rich aromatics. The advantages of
the present reaction are operational simplicity, low cost,
low toxicity, and easy availability of reaction materials.
Therefore, we believe that the present reactions are a use-
ful and environmentally benign method for the prepara-
tion of aromatic nitriles from aromatics directly. Further
synthetic study of the present method is underway in this
laboratory.
Synlett 2010, No. 7, 1067–1070 © Thieme Stuttgart · New York

1070
S. Ushijima, H. Togo
LETTER
stirred for 3 h at r.t. After the reaction, the mixture was
poured into aq sat. Na2SO3 solution and extracted with
CHCl3 (3 × 20 mL). The organic layer was dried over
Na2SO4, filtered, and evaporated to provide almost pure
2,4,5-trimethoxybenzonitrile (1156.1 mg) in 99% yield. If it
was necessary, it was recrystallized from a mixture of
hexane and EtOAc (1:1).
Most aromatic nitriles mentioned in this work are
commercially available and were identified by comparison
with the authentic samples.
2,4-Dimethoxybenzonitrile: mp 93–94 °C (commercial,
mp 93–94 °C). IR: 2219 cm–1. 1H NMR (500 MHz, CDCl3):
d = 3.86 (s, 3 H), 3.90 (s, 3 H), 6.46 (s, 1 H), 6.51 (d, J = 8.5
Hz, 1 H), 7.48 (d, J = 8.5 Hz, 1 H).
2,4,6-Trimethoxybenzonitrile: mp 139–140 °C
(commercial, mp 143–145 °C). IR: 2212 cm–1. 1H NMR
(500 MHz, CDCl3): d = 3.86 (s, 3 H), 3.89 (s, 6 H), 6.07 (s,
2 H).
6.85 (d, J = 8.2 Hz, 1 H), 6.99 (d, J = 7.7 Hz, 1 H), 7.47 (t,
J = 7.7 Hz, 1 H), 7.86 (d, J = 8.2 Hz, 1 H), 7.89 (d, J = 7.7
Hz, 1 H). HRMS (ESI): m/z calcd for C13H11O2N: 213.0784;
found: 21.0780.
4-Cyano-N,N-dimethylaniline: mp 74–75 °C (commercial,
mp 75 °C). IR: 2210 cm–1. 1H NMR (500 MHz, CDCl3): d =
3.04 (s, 6 H), 6.64 (d, J = 9.1 Hz, 2 H), 7.47 (d, J = 9.1 Hz,
2 H).
9-Cyanoanthracene: mp 173–175 °C (commercial, mp
173–177 °C). IR: 2212 cm–1. 1H NMR (500 MHz, CDCl3):
d = 7.59 (t, J = 8.5 Hz, 2 H), 7.73 (t, J = 8.5 Hz, 2 H), 8.09
(d, J = 8.5 Hz, 2 H), 8.43 (d, J = 8.5 Hz, 2 H), 8.69 (s, 1 H).
2-Cyano-N-benzylpyrrole: oil. IR: 2215 cm–1. 1H NMR
(400 MHz, CDCl3): d = 5.19 (s, 2 H), 6.19 (dd, J = 2.9, 2.7
Hz, 1 H), 6.80–6.86 (m, 2 H), 7.18 (d, J = 7.4 Hz, 2 H), 7.31–
7.38 (m, 3 H). HRMS (FAB): m/z [M + H]+ calcd for
C12H11N2: 183.0922; found: 183.0927.
3-Cyano-N-benzylpyrrole: oil. IR: 2224 cm–1. 1H NMR
(500 MHz, CDCl3): d = 5.06 (s, 2 H), 6.44 (d, J = 1.7 Hz,
1 H), 6.65 (s, 1 H), 7.11–7.17 (m, 3 H), 7.33–7.41 (m, 3 H).
HRMS (FAB): m/z [M + H]+ calcd for C12H11N2: 183.0922;
found: 183.0927.
2,3,4-Trimethoxybenzonitrile: mp 55–56 °C (commercial,
mp 56–57 °C). IR: 2226 cm–1. 1H NMR (400 MHz, CDCl3):
d = 3.87 (s, 3 H), 3.92 (s, 3 H), 4.06 (s, 3 H), 6.70 (d, J = 8.7
Hz, 1 H), 7.29 (d, J = 8.7 Hz, 1 H).
3-Cyanoindole: mp 177–179 °C (commercial, mp 179–182
°C). IR: 2227 cm–1. 1H NMR (500 MHz, CDCl3): d = 7.28–
7.36 (m, 2 H), 7.48 (d, J = 7.6 Hz, 1 H), 7.73 (s, 1 H), 7.78
(d, J = 7.3 Hz, 1 H), 8.91 (s, 1 H).
2-Cyanothiophene: oil. IR: 2222 cm–1. 1H NMR (500 MHz,
CDCl3): d = 7.14 (dd, J = 5.2, 3.7 Hz, 1 H), 7.62 (d, J = 5.2
Hz, 1 H), 7.64 (d, J = 3.7 Hz, 1 H).
5-Decyl-2-cyanothiophene: oil. IR: 2218 cm–1. 1H NMR
(500 MHz, CDCl3): d = 0.88 (t, J = 7.1 Hz, 3 H), 1.23–1.38
(m, 14 H), 1.67 (quint, J = 7.5 Hz, 2 H), 2.83 (t, J = 7.5 Hz,
2 H), 6.78 (d, J = 3.6 Hz, 1 H), 7.43 (d, J = 3.6 Hz, 1 H).
HRMS (FAB): m/z [M + H]+ calcd for C15H24NS: 250.1629;
found: 250.1636.
N-Methyl-3-cyanolindole: mp 60–61 °C (lit. 12 mp 60.5–
61.5 °C). IR: 2219 cm–1. 1H NMR (500 MHz, CDCl3): d =
3.75 (s, 3 H), 7.25 (t, J = 6.4 Hz, 1 H), 7.28–7.35 (m, 2 H),
7.44 (s, 1 H), 7.68 (d, J = 7.9 Hz, 1 H).
4-Methoxy-1-cyanonaphthalene: mp 100–102 °C
(commercial, mp 100–102 °C). IR: 2213 cm–1. 1H NMR
(400 MHz, CDCl3): d = 4.07 (s, 3 H), 6.84 (d, J = 8.2 Hz, 1
H), 7.59 (t, J = 8.2 Hz, 1 H), 7.69 (t, J = 8.2 Hz, 1 H), 7.86
(d, J = 8.2 Hz, 1 H), 8.17 (d, J = 8.2 Hz, 1 H), 8.32 (d, J = 8.2
Hz, 1 H).
5-Decyl-2-cyanofuran: oil. IR: 2229 cm–1. 1H NMR (500
MHz, CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.21–1.38 (m, 14
H), 1.65 (quint, J = 7.1 Hz, 2 H), 2.66 (t, J = 7.1 Hz, 2 H),
6.11 (d, J = 3.4 Hz, 1 H), 6.99 (d, J = 3.4 Hz, 1 H). HRMS
(FAB): m/z [M + H]+ calcd for C15H24NO: 234.1858; found:
234.1861.
3-Cyanobenzofuran: mp 90–91 °C (commercial, mp 93
°C). IR: 2211 cm–1. 1H NMR (500 MHz, CDCl3): d = 7.35 (t,
J = 7.5 Hz, 1 H), 7.44 (s, 1 H), 7.48–7.56 (m, 2 H), 7.67 (d,
J = 9.1 Hz, 1 H).
2-Methoxy-1-cyanonaphthalene: mp 96–97 °C (lit.13 mp
95–96 °C). IR: 2211 cm–1. 1H NMR (400 MHz, CDCl3): d =
4.08 (s, 3 H), 7.28 (d, J = 8.7 Hz, 1 H), 7.45 (t, J = 8.0 Hz, 1
H), 7.64 (t, J = 8.0 Hz, 1 H), 7.83 (d, J = 8.0 Hz, 1 H), 8.04
(d, J = 8.7 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H).
4,8-Dimethoxy-1-cyanonaphthalene: mp 126–129 °C. IR:
(12) Nakao, Y. J. Am. Chem. Soc. 2006, 128, 8146.
(13) Fuson, R. C. J. Org. Chem. 1948, 13, 484.
2211 cm–1. 1H NMR (400 MHz, CDCl3): d = 4.05 (s, 6 H),
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