compounds 1 to 8 (0.01–0.05 M), KCN (0.1–0.3 M) in a water–MeCN 1 : 3
(or 1 : 1) mixture in quartz tubes was flushed with nitrogen and irradiated
in a multilamp reactor (310 nm, see ESI{ for details). The final mixture was
then analyzed by HPLC and the yields were determined by comparison
with authentic samples of the benzonitriles. For preparative experiments
(30 mL of solvent), acetonitrile was eliminated in vacuo, water was added
and the mixture extracted with diethyl ether (in the synthesis of
4-cyanophenol acidification with HCl 0.1 M before extraction was
required). The raw product was then purified by column chromatography
(cyclohexane–ethyl acetate mixtures as the eluant). During the purification
of aminobenzonitriles, NEt3 (0.1%) was added to the eluant.
In the previous literature, there are sparse examples of
introducing a cyano group by photonucleophilic substitution
reactions.10 These have been usually carried out at a low
concentration (,1024 to 1023 M). Various mechanisms have been
proposed, including in one case a SN1 mechanism.11
The present reaction clearly involves a unimolecular path (see
again Scheme 1, path d).12 In fact, the quantum yield of reaction of
4-chloroaniline (1023 M) in water–acetonitrile 1 : 3 is Wr = 0.78
and aniline is the only product.13 The addition of KCN (from
1023 M to 0.02 M) did not affect the overall quantum yield (Wr),
while proportionally substituting the nitrile 9 for aniline. Likewise,
4-bromoaniline showed a Wr = 0.04 virtually independent of the
presence of KCN.
1 I. P. Beletskaya, A. S. Sigeev, A. S. Peregudov and P. V. Petrovskii,
J. Organomet. Chem., 2004, 689, 3810–3812; J. X. Wu, B. Beck and
R. X. Ren, Tetrahedron Lett., 2002, 43, 387–389.
2 M. Sundermeier, A. Zapf and M. Beller, Eur. J. Inorg. Chem., 2003,
3513–3526.
3 M. Sundermeier, A. Zapf, S. Mutyala, W. Baumann, S. Sans, S. Weis
and M. Beller, Chem. Eur. J., 2003, 9, 1828–1836.
4 K. M. Marcantonio, L. F. Frey, Y. Liu, Y. Chen, J. Strine, B. Phenix,
D. J. Wallace and C. Chen, Org. Lett., 2004, 6, 3723–3725.
5 M. Sundermeier, A. Zapf and M. Beller, Angew. Chem., Int. Ed., 2003,
42, 1661–1664.
6 M. Fagnoni and A. Albini, Acc. Chem. Res., 2005, 38, 713–721.
7 S. Protti, M. Fagnoni and A. Albini, Org. Biomol. Chem., 2005, 3,
2868–2871; M. De Carolis, S. Protti, M. Fagnoni and A. Albini, Angew.
Chem., Int. Ed., 2005, 44, 1232–1236.
8 The presence of water is crucial for the photoreactivity of 4-fluoroani-
line, see ref. 9.
9 M. Freccero, M. Fagnoni and A. Albini, J. Am. Chem. Soc., 2003, 125,
13182–13190.
10 For some examples see: M. Fagnoni and A. Albini, Photonucleophilic
Substitution Reactions, in Molecular and Supramolecular
Photochemistry, ed. V. Ramamurthy and K. Schanze, Dekker, New
York, 2006, vol. 14, pp. 131–177.
11 M. B. Groen and E. Havinga, Mol. Photochem., 1974, 6, 9–21.
12 Notice that previous literature favors either an ArSN2 pathway from the
triplet state or photoionization giving the aromatic radical cation
followed by addition of cyanide as the mechanism. As a matter of fact,
however, literature data on the photocyanation reactions of electron-rich
aromatic halides, e.g. of 4-chloroanisole, do fit an ArSN1 mechanism
and the Authors did not rule out this possibility. See for example: J. Den
Heijer, O. B. Shadid, J. Cornelisse and E. Havinga, Tetrahedron, 1977,
33, 779–786; K. Omura and T. Matsuura, J. Chem. Soc. D, 1969,
1394–1395; H. Lemmettyimen, J. Konijneberg, J. Cornelisse and
C. A. G. O. Varma, J. Photochem., 1985, 30, 315–338. For a more
detailed discussion of the unimolecular fragmentation of phenyl halides,
see: S. Protti, M. Fagnoni, M. Mella and A. Albini, J. Org. Chem., 2004,
69, 3465–3473.
13 Water in the solvent mixture dramatically increases the reaction
quantum yield (Wr) of 4-chloroaniline. Compare the present value with
that reported in MeCN (0.44) or MeOH (0.50), see ref. 14.
14 B. Guizzardi, M. Mella, M. Fagnoni, M. Freccero and A. Albini, J. Org.
Chem., 2001, 66, 6353–6363.
15 Triplet phenyl cations appear to be the most stable spin state when an
electron-donating group is present in the para position (see ref. 9 and
references cited therein). ortho and meta analogues are currently under
investigation.
The results are in accordance with the formation of triplet
phenyl cations as key intermediates, as expected from previous
studies.6,9,14 These species are either reduced in neat solvents or
trapped by cyanide. With respect to our previous work, new
phenyl cation precursors have been introduced, viz. 4-bromoani-
line, 4-fluorophenol and 2-chloroaniline, while 4-iodo- and
3-chloroaniline have been shown to be unsuitable.15
The photochemical method can not compete with the metal
mediated reactions in term of scope (the process being applicable
only to the synthesis of electron-rich benzonitriles) and requires
relatively dilute conditions (0.01 to 0.05 M). However, yields are
good to excellent, although reduction may compete to some extent
and this simple method offers some advantages. Thus, the use (and
the disposal) of delicate and toxic metal catalysts are avoided and
the mild conditions contrast with those required for the metal
catalyzed cyanation of aryl chlorides (e.g. high temperature and
the use of a pressure tube apparatus).3,16 In contrast to the
deactivation observed in the metal catalyzed process, the present
reaction adequately tolerates the use of an excess of KCN, a
relatively inexpensive cyanating agent. Indeed, the yields are
generally improved by increasing the amount of cyanide ion.
Furthermore, the photochemical method applies to precursors less
susceptible to thermal reactions. As an example, phenyl chlorides
and fluorides perform well here, while iodides and bromides are
mostly used in the thermal syntheses. In particular, the thermal
replacement of a fluoride with a cyano group met with some
success only with derivatives strongly activated by electron-
withdrawing groups.17
Likewise, phenyl esters, easily synthesized from the correspond-
ing phenols, have been rarely used for thermal substitution by a
cyano group,18 while these give good results in the present
reaction. This two step sequence results in the straightforward
substitution of a CN for an OH group via the esters. The
experimentally simple synthesis of benzonitriles presented here
overcomes some drawbacks of the thermal reactions, such as the
price of the catalyst and the removal of toxic metal waste. This
advantage and the large scope should make it a viable synthetic
alternative.
16 M. Sundermeier, A. Zapf, M. Beller and J. Sans, Tetrahedron Lett.,
2001, 42, 6707–6710; F. Jin and P. N. Confalone, Tetrahedron Lett.,
2000, 41, 3271–3273; R. K. Arvela and N. E. Leadbeater, J. Org. Chem.,
2003, 68, 9125–9128.
17 See for example: M. Leibovitch, G. Olovsson, J. R. Scheffer and
J. Trotter, J. Am. Chem. Soc., 1998, 121, 12755–12769; B. O. Patrick,
J. R. Scheffer and C. Scott, Angew. Chem., Int. Ed., 2003, 42, 3775–3777;
G. P. Ellis and T. M. Romney-Alexander, Chem. Rev., 1987, 87,
779–794.
Partial support of this work by MURST, Rome is gratefully
acknowledged.
18 Aryl mesylates and triflates has been used to some extent. See for
example: A. Zhang and J. L. Neumeyer, Org. Lett., 2003, 5, 201–203;
S.-F. Zhu, Y. Yang, L.-X. Wang, B. Liu and Q.-L. Zhou, Org. Lett.,
2005, 7, 2333–2335; K. Takagi and Y. Sakakibara, Chem. Lett., 1989,
1957–1958; V. Percec, J.-Y. Bae and D. H. Hill, J. Org. Chem., 1995, 60,
6895–6903.
Notes and references
{ Photochemical synthesis of benzonitriles. General procedure.
CAUTION: All the experiments must be carried out under a fume hood.
The aqueous phase must be conveniently disposed of. A solution of
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