L-proline-promoted Rosenmund-von Braun reaction

Article abstract of DOI:10.1055/s-2007-992409

L-Proline was identified as an effective additive to promote the Rosenmund-von Braun reaction at a lower temperature (80-120°C). This modified Rosenmund-von Braun cyanation of aryl bromides exhibits excellent functional-group compatibility, and provide an efficient and convenient approach for the synthesis of aryl nitriles. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-992409

LETTER
69
L-Proline-Promoted Rosenmund–von Braun Reaction
L
-Proline-Promote
e
d
Rosenm
u
p
nd–von
B
rau
i
n
Rea
c
n
tion g Wang,a Liping Kuang,a,b Zhengwei Li,a Ke Ding*a
a
Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences,
Guangzhou International Business Incubator A-3, Guangzhou Science Park, Guangzhou 510663, P. R. of China
Fax +86(20)32290485; E-mail: ding_ke@gibh.ac.cn
b
Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences,
Guangzhou International Business Incubator A-3, Guangzhou Science Park, Guangzhou 510663, P. R. of China
Received 25 September 2007
acids such as L-proline on the Rosenmund–von Braun re-
action.10
Abstract: L-Proline was identified as an effective additive to pro-
mote the Rosenmund–von Braun reaction at a lower temperature
(80–120 °C). This modified Rosenmund–von Braun cyanation of
aryl bromides exhibits excellent functional-group compatibility,
and provide an efficient and convenient approach for the synthesis
of aryl nitriles.
Initially, we examined the reaction of copper(I) cyanide
with 1-bromo-4-methoxybenzene (1a) in a variety of or-
ganic solvents at 120 °C as a model system to find the op-
timized reaction conditions.
Key words: L-proline, Rosenmund–von Braun reaction, copper,
aryl halides, aryl nitriles
Table 1 L-Proline-Catalyzed Cyanation of 1aa
CuCN, additive,
solvent, 120 °C
MeO
CN
MeO
Br
Aryl nitriles represent an important class of chemicals as
they are important ingredients for the preparation of dyes,
pesticides, agrochemicals, medicines, and bioactive natu-
ral products.1 They are also valuable intermediates in or-
ganic synthesis and can be easily transformed to a broad
spectrum of functionalities such as thiazoles, oxazoli-
dones, triazoles, and tetrazoles.2 A variety of synthetic
methods for the preparation of aryl nitriles have been de-
veloped,3 among which is the direct cyanation of aryl ha-
lides by copper(I) cyanide, known as Rosenmund–von
Braun reaction.4 The classical Rosenmund–von Braun
procedure requires a reaction temperature as high as 150–
250 °C, which makes it incompatible with sensitive sub-
strates. Recently, several palladium- or nickel-catalyzed
aryl cyanation approaches were reported.5,6 However,
many of these methods require special reagents such as
expensive and toxic phosphines as ligands etc.5f,s,t,6d Opti-
mization of the Rosenmund–von Braun reaction remains
one of most practicable approaches for the synthesis of
aryl nitriles because of its cost efficiency and easy opera-
tion.7 Herein we report an effective L-proline-promoted
Rosenmund–von Braun approach for the synthesis of aryl
nitriles from aryl iodides and aryl bromides, which
worked satisfactorily at 80–120 °C.
1a
2a
Entry Additive (equiv)
Solvent
Yield (%)b
15c
1
2
–
DMF
–
DMF
31
3
L-proline (1.0)
L-proline (1.0)
L-proline (0.5)
L-proline (0.2)
L-proline (0.1)
L-proline (1.0)
L-proline (1.0)
L-proline (1.0)
L-Tryptophane (1.0)
N-Methyl-glycine (1.0)
N,N-Dimethyl-glycine (1.0)
DMF
35c
4
DMF
81
5
DMF
40
6
DMF
27
7
DMF
23
8
Dioxane
MeCN
Toluene
DMF
Traced
28d
9
10
11
12
13
Traced
46
DMF
23
DMF
26
a Unless otherwise stated, the reaction conditions are: 1a (1.0 mmol),
CuCN (2.0 mmol), solvent (3 mL) at 120 °C for 45 h.
b Isolated yield.
Amino acids such as L-proline, glycine, N-methyl glycine,
N,N-dimethylglycine, pipecolinic acid, and alanine have
been identified as effective additives for the copper-cata-
lyzed C–N, C–C, or C–S bond formations.8 For example,
Ma demonstrated that L-proline could effectively promote
the copper-catalyzed reactions of aryl halides with sulfin-
c CuCN (1.2 mmol).
d Refluxing temperature.
ic acid salts, amines, and activated methylenes.9 These As summarized in Table 1, without additive the cyanation
successes thus led us to investigate the potential of amino of 1a was achieved only in poor yield, irrespective of
whether an approximately equal or stoichiometric amount
of copper(I) cyanide was added (entries 1 and 2). After
adding 1.0 equivalent L-proline, the cyanation yield was
significantly improved both in the presence of 1.2 equiv-
SYNLETT 2008, No. 1, pp 0069–0072
Advanced online publication: 11.12.2007
DOI: 10.1055/s-2007-992409; Art ID: W17807ST
x
x.
x
x.
2
0
0
7
© Georg Thieme Verlag Stuttgart · New York

70
D. Wang et al.
LETTER
alents or 2.0 equivalents copper(I) cyanide (entries 3 and Table 2 L-Proline-Promoted CuCN-Catalyzed Cyanation of Aryl
Bromides and Iodidesa
4). Especially, under the conditions of entry 4, an 81%
isolated yield of the product 2a was obtained. This high-
2.0 equiv CuCN,
1.0 equiv
L-proline
lighted the promoting function of L-proline on the Rosen-
mund–von Braun reaction. It was also revealed that 1.0
equivalent of L-proline seemed to be essential for the pro-
motion of Rosenmund–von Braun reaction. When 0.5, 0.2
or 0.1 equivalent of L-proline was used, only a slight im-
provement was observed (entries 5, 6, or 7). We further
examined the influence of different solvents on this L-pro-
line-promoted Rosenmund–von Braun reaction, and
found that DMF was the best medium for this reaction.
Other solvents such as dioxane, toluene, or acetonitrile
were detrimental to the reaction. The promoting potentials
of other amino acids such as tryptophane, N-methylgly-
cine and N,N-methylglycine on Rosenmund–von Braun
reaction were also investigated under the optimized con-
ditions. Unfortunately, none of them seemed to have any
effect on the Rosenmund–von Braun reaction (entries 11–
13).
CN
X
DMF, 120 °C, 45 h
R
R
1
2
Entry R
X
Yield of 2
(%)b
1
4-Methoxy
4-Nitro
H
I
98c (2a)
92c (2b)
90c (2c)
91c (2d)
81 (2a)
76 (2c)
89 (2e)
84d (2f)
74 (2g)
85 (2h)
85 (2i)
2
I
3
I
4
2-Amino-4-chloro-5-fluro
4-Methoxy
I
5
Br
Br
Br
6
H
7
2,4-Dimethoxy-6-methyl
2,4-Dimethoxy-6-methyl
3,4,5-Trimethoxy
4-Acetylamino
4-Hydroxyl
Using L-proline as the ligand, we further tested the cou-
pling reaction of copper(I) cyanide with a variety of aryl
halides. We have demonstrated that L-proline could effi-
ciently promote the Rosenmund–von Braun cyanation of
1-bromo-4-methoxybenzene in DMF after 45 hours at 120
°C. Then we first investigated the cyanation of more ac-
tive aryl iodides under similar conditions. Not surprising-
ly, all the examined aryl iodides gave 90–98% yields
when the reaction was carried out in DMF at 80 °C in 24
hours, no matter they bear electron-donating or electron-
withdrawing substituents (Table 2, entries 1–4). The effi-
cacy of L-proline-promoted Rosenmund–von Braun cya-
nation was further extended to other aryl bromides with
different substituents. All the less-active aryl bromides
also worked well except the fact that the coupling reaction
8
1,3-Dibromo
9
Br
Br
Br
Br
10
11
12
3-Amino
69 (2j)
Br
13
87 (2k)
78 (2l)
Br
14
OMe
of aryl bromides gave a slightly lower yield and required 15
4-Methoxy-carbonyl
Br
Br
65 (2m)
56 (2b)
57e (2n)
a higher temperature (120 °C), comparing with that of cor-
responding aryl iodides (entries 1–3, 5, 6, and 16). For ex-
16
4-Nitro
ample, the cyanation of 1-bromo-4-methoxybenzene
(entry 5) required a temperature of 120 °C for 45 hours
and an 81% isolated yield was obtained. When 1-iodo-4-
methoxybenzene (entry 1) was used, it only required a
temperature of 80 °C for 24 hours and the isolated yield
was up to 98%. Our results also clearly revealed that elec-
tron-rich aryl bromides were preferred for the L-proline-
promoted Rosenmund–von Braun reaction (entries 5–14).
The steric nature of the substituents does not seem to have
much influence on the cyanation of the corresponding
substrates (entries 4, 7, 8, and 14). When 2,4-dibromo-
1,5-dimethoxy-3-methylbenzene was utilized, both
17
4-(4¢-Bromo-phenyl)carbonyl Br
Br
18
78 (2o)
O
N
a Unless otherwise stated, the reaction conditions are: 1 (1.0 mmol),
CuCN (2.0 mmol), L-proline (1.0 mmol), DMF (3 mL) at 120 °C for
45 h.
b Isolated yield.
c 80 °C, 24 h.
d Both 3-bromo-4,6-dimethoxy-2-methylbenzonitrile (2f-1, 62%) and
4,6-dimethoxy-2-methylbenzene-1,3-dinitrile (2f-2, 22%) were iso-
lated.
monocyano- and dicyano products were isolated (entry 8). e Only monocyano product was isolated.
When the aryl bromides carried a strongly electron-with-
drawing moiety such as carboxylic ester or nitro (entries
15 and 16), only 56–65% yields were obtained. The cya-
nation of bis(4-bromophenyl)methanone also gave a rela-
tively low yield (57%, entry 17) and only monocyano
product was isolated. This may be due to the side reaction
of copper(I) cyanide with the carbonyl group in the sub-
strate. It should be noted that this L-proline-promoted
Rosenmund–von Braun cyanation is compatible with
amino, hydroxyl, carbonyl, carboxylic ester, and other ac-
tive functional groups (entries 4, 11, 12, 15). Furthermore,
this L-proline-promoted Rosenmund–von Braun reaction
Synlett 2008, No. 1, 69–72 © Thieme Stuttgart · New York

LETTER
L-Proline-Promoted Rosenmund–von Braun Reaction
71
A. S.; Toyota, K.; Yoshifuji, M.; Ozawa, F. Tetrahedron
is also applicable to the cyanation of heteroaryl bromide
(entry 18) and gave a good product yield.
Lett. 2005, 46, 8645. (m) Veauthier, J. M.; Carlson, C. N.;
Collis, G. E.; Kiplinger, J. L.; John, K. D. Synthesis 2005,
2683. (n) Hatsuda, M.; Seki, M. Tetrahedron 2005, 61,
9908. (o) Takanami, T.; Hayashi, M.; Chijimatsu, H.-i.;
Inoue, W.; Suda, K. Org. Lett. 2005, 7, 3937. (p) Hatsuda,
M.; Seki, M. Tetrahedron Lett. 2005, 46, 1849. (q) Stazi,
F.; Palmisano, G.; Turconi, M.; Santagostino, M.
Tetrahedron Lett. 2005, 46, 1815. (r) Weissman, S. A.;
Zewge, D.; Chen, C. J. Org. Chem. 2005, 70, 1508.
(s) Marcantonio, K. M.; Frey, L. F.; Liu, Y.; Chen, Y.;
Strine, J.; Phenix, B.; Wallace, D. J.; Chen, C.-Y. Org. Lett.
2004, 6, 3723. (t) Yang, C.; Williams, J. M. Org. Lett. 2004,
6, 2837. (u) Schareina, T.; Zapf, A.; Beller, M. Chem.
Commun. 2004, 12, 1388. (v) Chidambaram, R.
In summary, we have successfully demonstrated that L-
proline could efficiently promote the Rosenmund–von
Braun reaction of copper(I) cyanide with aryl halides at a
lower temperature (80–120 °C). The cyanation of both
aryl iodides and aryl bromides can be achieved efficiently
under the reported conditions. Furthermore, this L-pro-
line-promoted Rosenmund–von Braun cyanation exhibits
excellent functional-group compatibility. Our report may
provide an efficient and convenient approach for the con-
temporary synthesis of aryl nitriles.
Tetrahedron Lett. 2004, 45, 1441. (w) Erker, T.; Nemec, S.
Synthesis 2004, 23. (x) Ramnauth, J.; Bhardwaj, N.; Renton,
P.; Rakhit, S.; Maddaford, S. P. Synlett 2003, 2237.
(y) Sundermeier, M.; Zapf, A.; Beller, M. Angew. Chem. Int.
Ed. 2003, 42, 1661.
Acknowledgment
We thank the Chinese Academy of Sciences (Grant KSCX2-YW-
R-27) and Guangzhou Institute of Biomedicine and Health for their
financial support. Prof. Dawei Ma at Shanghai Institute of Organic
Chemistry (CAS) is gratefully acknowledged for his helpful discus-
sions and advice.
(6) For the nickel-catalyzed cyanation of aryl halides, see:
(a) Cassar, L.; Foà, M.; Montanari, F.; Marinelli, G. P.
J. Organomet. Chem. 1979, 173, 335. (b) Sakakibara, Y.;
Okuda, F.; Shimoyabashi, A.; Kirino, K.; Sakai, M.; Uchino,
N.; Takagi, K. Bull. Chem. Soc. Jpn. 1988, 61, 1985.
(c) Sakakibara, Y.; Ido, Y.; Sasaki, K.; Sakai, M.; Uchino, N.
Bull. Chem. Soc. Jpn. 1993, 66, 2776. (d) Arvela, R. K.;
Leadbeater, N. E. J. Org. Chem. 2003, 68, 9122.
References and Notes
(1) Kleemann, A.; Engel, J.; Kutscher, B.; Reichert, D.
Pharmaceutical Substances: Syntheses, Patents,
(7) (a) Cristau, H. J.; Ouali, A.; Spindler, J. F.; Taillefer, M.
Chem. Eur. J. 2005, 11, 2483. (b) Zanon, J.; Klapers, A.;
Buchald, S. L. J. Am. Chem. Soc. 2003, 126, 2890. (c) Wu,
J. X.; Beck, B.; Ren, R. X. Tetrahedron Lett. 2002, 43, 387.
(d) Schareina, T.; Zapf, A.; Beller, M. Tetrahedron Lett.
2005, 46, 2585.
Applications, 4th ed.; Georg Thieme: Stuttgart, 2001.
(2) Larock, R. C. Comprehensive Organic Transformations. A
Guide to Functional Group Preparations; VCH: New York,
1989.
(3) (a) Hagedorn, F.; Gelbke, H. P. In Ullmanns Enzyklopädie
der Technischen Chemie, 4th ed., Vol. 17; Bartholomé, E.;
Biekert, E.; Hellmann, H.; Ley, H.; Weigert, W. M.; Weise,
E., Eds.; Verlag Chemie: Weinheim, 1979, 333–338.
(b) Ellis, G. P.; Romney-Alexander, T. M. Chem. Rev. 1987,
87, 779. (c) Grushin, V. V.; Alper, H. Chem. Rev. 1994, 94,
1047. (d) Subramanian, L. R. Science of Synthesis, Vol. 19;
Georg Thieme: Stuttgart, 2004, 163.
(4) (a) Rosenmund, K. W.; Struck, E. Ber. Dtsch. Chem. Ges.
1919, 2, 1749. (b) Mowry, D. F. Chem. Rev. 1948, 42, 189.
(c) Friedrich, K.; Wallenfels, K. In The Chemistry of the
Cyano Group; Rappoport, Z., Ed.; Interscience: London,
1970, 67. (d) Lindley, J. Tetrahedron 1984, 40, 1433.
(e) Kurtz, P. In Houben–Weyl, Methoden der Organischen
Chemie, 4th ed., Part III, Vol. 8; Müller, E., Ed.; Georg
Thieme: Stuttgart, 1952, 302.
(5) For the palladium-catalyzed cyanation of aryl halides, see:
(a) Takagi, K. Handbook of Organopalladium Chemistry for
Organic Synthesis, Vol. 1; John Wiley and Sons, Inc.: New
York, 2002, 657–672. (b) Sundermeier, M.; Zapf, A.;
Mutyala, S.; Baumann, W.; Sans, J.; Weiss, S.; Beller, M.
Chem. Eur. J. 2003, 9, 1828; and the references therein.
(c) Polshettiwar, V.; Hesemann, P.; Moreau, J. J. E.
Tetrahedron 2007, 63, 6784. (d) Dolakova, P.;
(8) (a) Guo, X.; Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y. Adv. Synth.
Catal. 2006, 348, 2197. (b) Ma, D.; Liu, F. Chem. Commun.
2004, 1934. (c) Ma, D.; Zhang, Y.; Yao, J.; Wu, S.; Tao, F.
J. Am. Chem. Soc. 1998, 120, 12459. (d) Zhang, H.; Cai, Q.;
Ma, D. J. Org. Chem. 2005, 70, 5164. (e) Ma, D.; Xia, C.
Org. Lett. 2001, 3, 2583. (f) Ma, D.; Cai, Q.; Zhang, H. Org.
Lett. 2003, 5, 2453. (g) Ma, D.; Cai, Q. Org. Lett. 2003, 5,
3799. (h) Deng, W.; Zou, Y.; Wang, Y. F.; Liu, L.; Guo, Q.
X. Synlett 2004, 1254. (i) Deng, W.; Zhang, Ch.; Liu, M.;
Zou, Y.; Liu, L.; Guo, Q. X. Chin. J. Chem. 2005, 23, 1241.
(j) Pan, X.; Cai, Q.; Ma, D. Org. Lett. 2004, 6, 1809.
(9) (a) Xie, X.; Chen, Y.; Ma, D. J. Am. Chem. Soc. 2006, 128,
16050. (b) Zhu, W.; Ma, D. J. Org. Chem. 2005, 70, 2696.
(c) Ma, D.; Cai, Q.; Zhang, H. Org. Lett. 2003, 5, 2453.
(d) Xie, X.; Cai, G. R.; Ma, D. Org. Lett. 2005, 7, 4693.
(e) Lu, B.; Ma, D. Org. Lett. 2006, 8, 6115.
(10) General Procedure for the l-Proline-Promoted
Rosenmund–von Braun Reaction
To a mixture of CuCN (2 mmol), L-proline (1 mmol), and
anhyd DMF (3 mL) under argon, aryl bromide (1 mmol) was
added at r.t. The mixture was stirred at 120 °C for 45 h. After
the resulting suspension was cooled to r.t., diluted with
EtOAc (15 mL), and washed with H2O (3 × 4 mL). The
organic phase was dried over Na2SO4, concentrated, and the
residue was purified by flash chromatography on silica with
EtOAc–hexane to yield the product.
Masojidkova, M.; Holy, A. Heterocycles 2007, 71, 1107.
(e) Cheng, Y.; Duan, Z.; Li, T.; Wu, Y. Synlett 2007, 543.
(f) Littke, A.; Soumeillant, M.; Kaltenbach, R. F. III;
Cherney, R. J.; Tarby, C. M.; Kiau, S. Org. Lett. 2007, 9,
1711. (g) Schareina, T.; Zapf, A.; Maegerlein, W.; Mueller,
N.; Beller, M. Tetrahedron Lett. 2007, 48, 1087. (h)Dobbs,
K. D.; Marshall, W. J.; Grushin, V. V. J. Am. Chem. Soc.
2007, 129, 30. (i) Zhang, Z.; Liebeskind, L. S. Org. Lett.
2006, 8, 4331. (j) Grossman, O.; Gelman, D. Org. Lett.
2006, 8, 1189. (k) Chobanian, H. R.; Fors, B. P.; Lin, L. S.
Tetrahedron Lett. 2006, 47, 3303. (l) Jensen, R. S.; Gajare,
Analytical Data of Compounds 2a–o
4-Methoxybenzonitrile (2a): ESI-MS: m/z = 134 [M + H]+.
1H NMR (400 MHz, CDCl3): d = 3.84 (3 H, s), 6.94 (2 H, d,
J = 8.8 Hz), 7.56 (2 H, d, J = 8.4 Hz).
4-Nitrobenzonitrile (2b): 1H NMR (400 MHz, CDCl3): d =
7.88 (2 H, d, J = 8.8 Hz), 7.37 (2 H, d, J = 8.8 Hz).
Benzonitrile (2c): ESI-MS: m/z = 104 [M + H]+. 1H NMR
Synlett 2008, No. 1, 69–72 © Thieme Stuttgart · New York

72
D. Wang et al.
LETTER
(400 MHz, CDCl3): d = 7.46–7.67 (5 H, m). 2-Amino-4-
chloro-5-fluorobenzonitrile (2d): 1H NMR (400 MHz,
DMSO-d): d = 6.18 (2 H, br), 6.94 (1 H, d, J = 6.8 Hz), 7.58
(1 H, d, J = 9.2 Hz).
J = 9.6 Hz), 7.55 (2 H, d, J = 8.8 Hz).
3-Aminobenzonitrile (2j): ESI-MS: 117 [M – H]+. 1H NMR
(400 MHz, CDCl3): d = 3.86 (1 H, s), 6.85 (1 H, d, J = 8.0
Hz), 6.90 (1 H, s), 7.01 (1 H, d, J = 7.2 Hz), 7.22 (1 H, t,
J = 8.0 Hz).
2,4-Dimethoxy-6-methylbenzonitrile (2e): 1H NMR (400
MHz, CDCl3): d = 2.45 (3 H, s), 3.81 (3 H, s), 3.86 (3 H, s),
6.27 (1 H, d, J = 2.0 Hz), 6.36 (1 H, d, J = 1.6 Hz).
3-Bromo-4,6-dimethoxy-2-methylbenzonitrile (2f-1): ESI-
MS: m/z = 255 [M]+, 257 [M + 2]+. HRMS (EI): m/z calcd
for C10H10BrNO2 [M]+: 254.9895; found: 254.9868. 1H
NMR (400 MHz, CDCl3): d = 2.59 (3 H, s), 3.94 (3 H, s),
3.96 (3 H, s), 6.34 (1 H, s)
1-Naphthonitrile (2k): 1H NMR (400 MHz, CDCl3): d = 8.14
(1 H, d, J = 8.8 Hz), 7.98 (1 H, d, J = 8.4 Hz), 7.80–7.84 (2
H, m), 7.58–7.62 (1 H, t, J = 8.4 Hz), 7.50–7.54 (1 H, t,
J = 8.0 Hz), 7.40–7.44 (1 H, t, J = 8.0 Hz).
3-Methoxy-2-naphthonitrile (2l): 1H NMR (400 MHz,
CDCl3): d = 3.95 (3 H, s), 7.12 (1 H, s), 7.37 (1 H, t, J = 8.0
Hz), 7.49–7.52 (1 H, t, J = 8.4 Hz), 7.68 (1 H, d, J = 8.0 Hz),
7.71 (1 H, d, J = 8.0 Hz), 8.08 (1 H, s).
4,6-Dimethoxy-2-methylisophthalonitrile (2f-2): ESI-MS:
m/z = 202 [M]+. HRMS (EI): m/z calcd for C11H10N2O2 [M]+:
202.0742; found: 202.0747. 1H NMR (400 MHz, CDCl3):
d = 2.66 (3 H, s), 4.00 (6 H, s), 6.34 (1 H, s).
Methyl 4-cyanobenzoate (2m): 1H NMR (400 MHz,
CDCl3): d = 3.96 (3 H, s), 7.74 (2 H, d, J = 6.4 Hz), 8.13 (2
H, d, J = 6.4 Hz).
3,4,5-Trimethoxybenzonitrile (2g): 1H NMR (400 MHz,
CDCl3): d = 3.88 (6 H, s), 3.90 (3 H, s), 6.86 (2 H, s).
N-(4-Cyanophenyl)acetamide (2h): 1H NMR (400 MHz,
CDCl3): d = 2.15 (3 H, s), 7.46 (1 H, s), 7.53 (2 H, d, J = 8.8
Hz), 7.58 (2 H, d, J = 8.8 Hz).
4-(4-Bromobenzoyl)benzonitrile (2n): ESI-MS: m/z 285
[M – H]+, 286 [M – 2]+. 1H NMR (400 MHz, CDCl3): d = 7.66
(4 H, s), 7.79 (2 H, d, J = 8.0 Hz), 7.86 (2 H, d, J = 8.4 Hz).
6-Methoxypyridine-3-carbonitrile (2o): ESI-MS: m/z = 135
[M + H]+. 1H NMR (400 MHz, CDCl3): d = 3.99 (3 H, s),
6.80 (1 H, d, J = 8.4 Hz), 7.76 (1 H, dd, J = 2.0, 8.4 Hz), 8.48
(1 H, s).
4-Hydroxybenzonitrile (2i): ESI-MS: 118 [M – H]+. 1H
NMR (400 MHz, CDCl3): d = 6.01 (1 H, s), 6.90 (2 H, d,
Synlett 2008, No. 1, 69–72 © Thieme Stuttgart · New York