LETTER
Synthesis of Phthalonitriles
2289
Table 1 Palladium-Catalyzed Cyanation of Various o-Dibromobenzenes (continued)
Substrate
Producta
Temp (°C)
Time (h)
4
Yield (%)
Br
Br
CN
CN
18a
18b
100
78
N
N
Br
Br
CN
CN
O
O
19a
19b
110
1
93
O
O
a Physical data of all synthesized phthalonitriles were in agreement with the data reported in the literature.
The specific influence of the para substituents on the re- References and Notes
activity of the bromo atoms can be seen especially clearly
(1) (a) De la Torre, G.; Claessens, C. G.; Torres, T. Chem.
Commun. 2007, 2000. (b) Hanack, M.; Heckmann, H.;
Polley, R. Methods of Organic Chemistry (Houben-Weyl);
Thieme: Stuttgart, 1997, 717. (c) Leznoff, C. C.
with 4,5-dibromo-2-nitroaniline (14a):13 only the bromo
atom in the para position to the electron-donating NH2
group is exchanged against the CN group, the strong elec-
tron-attracting NO2 group (sp-NO2 = 0.778) in para posi-
tion to the second bromo atom prevents its exchange. This
is supported by the results with 1,2-dibromo-4,5-dini-
trobenzene (15a)14 which does not react with formation of
the corresponding dinitrophthalonitrile 15b.
Phthalocyanines: Properties and Applications; VCH
Publishers, Inc.: New York, 1989, 1. (d) Hanack, M.; Lang,
M. Adv. Mater. 1994, 6, 819.
(2) 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.
(3) Friedman, L.; Shechter, H. J. Org. Chem. 1961, 26, 2522.
(4) Hanack, M.; Drechsler, U. Synlett 1998, 1207.
(5) (a) Zhu, Y.-Z.; Cai, C. Eur. J. Org. Chem. 2007, 2401.
(b) Weissman, S. A.; Zewge, D.; Chen, C. J. Org. Chem.
2005, 70, 1508. (c) Sundermeier, M.; Zapf, A.; Beller, M.
Eur. J. Inorg. Chem. 2003, 3513.
(6) (a) Tsuji, J. Transition Metal Reagents and Catalysts –
Innovations in Organic Synthesis; John Wiley and Sons:
Chichester, 2000. (b) Brandsma, L.; Vasilevsky, S. F.;
Verkruijsse, H. D. Application of Transition Metal Catalysts
in Organic Synthesis; Springer: Berlin, Heidelberg, 1999,
149. (c) Heck, R. F. Palladium Reagents in Organic
Syntheses; Academic Press: London, 1985.
Contrary to 1,2-dibromo-4,5-dinitrobenzene (15a), 4,5-
dibromophthalonitrile (16a)15 also with two but lesser
electron-attracting CN groups (sp-CN = 0.628) in para po-
sition to the bromine atoms reacts with formation of
1,2,4,5-tetracyanobenzene (11b) although in somewhat
lower yields.
In spite of the fact that 3,4-dibromophenol (10a) was con-
verted in high yields into the 4-hydroxyphthalonitrile
(9b), 4,5-dibromocatechol (17a) even after a longer reac-
tion time could not be reacted to form 4,5-dihydroxy-
phthalonitrile (17b). This is probably due to a partial
decomposition of the catalyst because of its reaction with
catechol 17a. 2,3-Dibromopyridine (18a) also reacts un-
der the applied conditions with formation of 2,3-di-
cyanopyridine (18b) in good yield. Only one
dibromonaphthalene was investigated: 6,7-dibromo-2,2-
dimethylnaphtho[2,3-d][1,3]dioxole (19a)16 was convert-
ed in a yield of 93% into the corresponding naphthaloni-
trile 19b17 within one hour at 110 °C.
(7) Synthesis of Substituted Phthalonitriles – General
Procedure
A 25 mL two-neck round-bottom flask was charged with 1
mmol of o-dibromobenzene in DMAC (2 mL) and PMHS
(20 mg) was added at r.t. The reaction mixture was heated to
the required temperature (Table 1) and Pd2 (dba)3 (20 mg, 2
mol%) and DPPF (15 mg, 2.7 mol%) were added.
Afterwards, Zn(CN)2 (117 mg, 1 mmol) was added in 4–5
portions during the time mentioned in Table 1 till TLC
indicated completion of the reaction. The reaction mixture
was cooled, diluted with EtOAc and filtered. Filtrate was
washed with H2O, dried with MgSO4, and concentrated in
vacuo. The crude product was purified by column
chromatography using CH2Cl2 as eluent.
In conclusion we have described another easier alternative
to Rosenmund–von Braun reaction, which can be easily
used to synthesize mono- and disubstituted phthalonitriles
containing various functional groups.
(8) Martin, M. T.; Liu, B.; Cooley, B. E. Jr.; Eaddy, J. F.
Tetrahedron Lett. 2007, 48, 2555.
(9) (a) Takagi, K.; Sasaki, K.; Sakakibara, Y. Bull. Chem. Soc.
Jpn. 1991, 64, 1118. (b) Maligres, P. E.; Waters, M. S.;
Fleitz, F.; Askin, D. Tetrahedron Lett. 1999, 40, 8193.
(c) Jin, F.; Confalone, P. N. Tetrahedron Lett. 2000, 41,
3271.
Acknowledgment
Z. Iqbal thanks Deutscher Akademischer Austausch Dienst
(DAAD) and Higher Education Commission (HEC) Pakistan for
financial support.
(10) (a) Synthesis of 1,2-Dibromo-4-tert-butylbenzene (2a)
To a solution of 1-bromo-4-tert-butylbenzene (8 g, 0.04
mol) in CCl4 (5 mL) in the presence of a small amount of
iron powder was added a solution of bromine (9.5 g, 0.12
mol) in CCl4 (4 mL) at 5 °C over 10 min. The mixture was
stirred at 15 °C for 2 h. Solvent was evaporated and product
was purified by column chromatography using CH2Cl2–
hexane (1:1) as eluent; yield 11 g (92%). 1H NMR (400
Synlett 2008, No. 15, 2287–2290 © Thieme Stuttgart · New York