Con ver sion of Alcoh ols, Th iols, a n d Tr im eth ysilyl Eth er s to Alk yl
Cya n id es Usin g Tr ip h en ylp h osp h in e/
2,3-Dich lor o-5,6-d icya n oben zoqu in on e/n -Bu 4NCN
Nasser Iranpoor,* Habib Firouzabadi,* Batool Akhlaghinia,† and Najmeh Nowrouzi
Department of Chemistry, Shiraz University, Shiraz, 71454 Iran
iranpoor@chem.susc.ac.ir; firouzabadi@chem.susc.ac.ir
Received August 23, 2003
Triphenylphosphine and 2,3-dichloro-5,6-dicyanobenzoquinone afford an adduct, which in the
presence of n-Bu4NCN converts alcohols, thiols, and trimethylsilyl ethers into their corresponding
alkyl cyanides in good to excellent yields at room temperature. This method is highly selective for
the conversion of 1° alcohols in the presence of 2° and 3° ones, thiols and silyl ethers.
SCHEME 1
In tr od u ction
The nitrile functional group is widely recognized as a
useful intermediate in organic synthesis.1,2 Different
synthetic methodologies have been reported for the
introduction of this group to organic compounds.3 In
replacement of the leaving groups with cyanide ions in
organic halogen compounds, aryl sulfonates, alcohols,
esters, ethers, nitro or amino compounds, and diazonium
salts could be used as suitable substrates for this type of
reaction.4 Among these functionalities, alkyl halides and
alcohols are used more frequently for this transformation.
For primary halides, the reaction is usually substitution;4
however, with secondary and tertiary alkyl halides,
competition between substitution and elimination results
in low yields of nitriles. The transformation of alcohols
to nitriles is an important method for the elongation of
the carbon chain and is usually performed through prior
conversion of the hydroxyl group to leaving groups such
as halides and sullfonates. The more simplified one-pot
method for the conversion of alcohols into cyanides based
on the concept of the Mitsunobu reaction using HCN/
PPh3/DEAD in moderate yields is described.5-7 The use
TABLE 1. Con ver sion of Ben zyl Alcoh ol to Ben zyl
Cya n id e Usin g n -Bu 4NCN in th e P r esen ce of P P h 3 a n d
Differ en t Rea gen ts in Aceton itr ile a t Room Tem p er a tu r e
entry
mixed reagent
time (h)
conversion %a
1
2
3
4
5
6
7
PPh3/DDQ
PPh3/p-chloranil
PPh3/DEAD
PPh3/DEACD
PPh3/TCNE
PPh3/tetracyclone
PPh3/PTAD
immediately
100
7
10
0
0
0
24
24
24
24
24
24
0
a
GC yield using an internal standard.
of n-Bu3P/CCl4/KCN/18-crown-65f for the conversion of
only primary alcohols to nitriles and the modification of
the Mitsunobu reaction using acetone cyanohydrin as a
source of HCN are also reported.8,9 However, this latter
reaction gives low yields for hindered primary alcohols
(17%) and also for secondary alcohols (10-58%).
In this paper, we report a novel and simple method
for the efficient conversion of 1°, 2°, and 3° alcohols as
well as thiols and trimethylsilyl ethers into their corre-
sponding nitriles.
† On leave from the Department of Chemistry, Damqhan University
of Basic Sciences, Damqhan, Iran.
(1) (a) Lease, T. G.; Shea, K. J . J . Am. Chem. Soc. 1993, 115, 2248.
(b) Gwaltney, S. L.; Sakata, S. T.; Shea, K. J . J . Org. Chem. 1996, 61,
7438. (c) Fleming, F. F.; Huang, A.; Sharief, V. A.; Pu, Y. J . Org. Chem.
1997, 62, 3063.
(2) The Chemistry of the Triple-Bond Functional Groups; Patai, S.,
Rappoport, Z., Eds.; Wiley-Interscience: New York, 1983.
(3) The Chemistry of Cyano Group; Rappoport, Z., Ed.; Wiley-
Interscience: New York, 1970.
(4) Kornblum, N.; Smiley, R. A.; Blackwood, R. K.; Iffland, D. C. J .
Am. Chem. Soc. 1955, 77, 6269.
(5) (a) Castro, B. R. Org. React. 1983, 29, 1. (b) Grundman, C. In
Mothoden der Organischen Chemie (Houben-Weyl); Georg Thieme
Verlag: Stuttgart, Germany, 1985; Vol. E5, p 1474 (c) Brett, D.;
Downie, I. M.; Lee, J . B. J . Org. Chem. 1967, 32, 855. (d) Castro, B.;
Selve, C. Bull. Soc. Chim. Fr. 1971, 2296. (e) Biogegrain, R.; Castro,
B.; Selve, C. Tetrahedron Lett. 1975, 30, 2529. (f) Mizuno, A.; Hamada,
Y.; Shioiri, T. Synthesis 1980, 1007. (g) Davis, R.; Untch, K. G. J . Org.
Chem. 1981, 46, 2985.
Resu lts a n d Discu ssion
Recently, we have reported on the application of PPh3/
DDQ/R4NX (X ) Cl, Br, I) for the conversion of alcohols,
thiols, and selenols into their corresponding alkyl ha-
(6) (a) Mitsunobu, O. Synthesis 1981, 1. (b) Hughes, D. L. Org. React.
1992, 42, 335.
(7) Loibner, H.; Zbiral, E. Helv. Chim. Acta 1976, 59, 2100.
(8) Bogdan, K. W. Synth. Commun. 1993, 23, 2481.
(9) Aesa, M. C.; Baan, G.; Novak, L.; Szantay, C. Synth. Commun.
1995, 25, 2575.
10.1021/jo035238v CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/12/2004
2562
J . Org. Chem. 2004, 69, 2562-2564