A novel and convenient transformation of nitriles to aldehydes

Article abstract of DOI:10.1016/S0040-4039(02)00027-8

Various aromatic nitriles are reduced to the corresponding aldehydes by platinum(IV) oxide in aqueous formic acid with yields ranging from 76 to 94%. This mild method may be generally applied to multi-step organic synthesis.

Full text of DOI:10.1016/S0040-4039(02)00027-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1395–1396
A novel and convenient transformation of nitriles to aldehydes
Fred Xi,* Fred Kamal and Mark A. Schenerman
MedImmune, Inc., 35 West Watkins Mill Road, Gaithersburg, MD 20878, USA
Received 7 November 2001; revised 19 December 2001; accepted 20 December 2001
Abstract—Various aromatic nitriles are reduced to the corresponding aldehydes by platinum(IV) oxide in aqueous formic acid
with yields ranging from 76 to 94%. This mild method may be generally applied to multi-step organic synthesis. © 2002 Elsevier
Science Ltd. All rights reserved.
Aldehydes are important intermediates in organic syn-
thesis due to their reactivity. Three principal methods
Formic acid not only serves as a solvent, but also as a
hydrogen source in the reaction. Reaction of formic
acid with platinum oxide liberates hydrogen and carbon
can be used for the reduction of nitriles to aldehydes:
1
8
(
1) Stephen reduction, in which nitriles are reduced to
dioxide and leads to formation of more reactive plat-
aldehydes by stannous chloride and hydrogen chloride
under anhydrous conditions; (2) using metal hydrides
3
inum species capable of reducing nitriles to the corre-
sponding aldimines. The aldimines are rapidly
hydrolyzed to aldehydes (Scheme 1).
2
3
such as LiAlH , LiAlH(OEt) , DIBAL, NaH AlEt ;
4
3
2
2
(
3) reduction by 150% (w/w) Raney nickel, first
4–6
reported by Backeberg and Staskun. A comprehen-
sive reagent list for this transformation has been com-
piled by Larock.
Representative reaction times and yields are given in
Table 1. It should be noted that better yields are
achieved with shorter reaction times when platinum is
added portionwise at certain intervals. In addition, the
double bond in entry 4 remains unreacted when treated
7
In this communication, we wish to report a convenient
method to reduce nitriles to aldehydes by platinum(IV)
oxide under mild conditions. A typical procedure is
illustrated by the preparation of p-methoxybenzalde-
hyde: a mixture of 4-methoxybenzonitrile (10 mmol)
and platinum oxide (1 mmol) in 15 mL of 80% aqueous
formic acid was stirred at 55–60°C for 7 h. Platinum
was removed by filtration. Water (15 mL) was added to
the filtrate and the product was extracted with ether
with PtO under these reaction conditions, the same
2
observation were reported by Staskun and van Es when
5,9
Raney nickel used.
Attempted reduction of an
aliphatic nitrile (entry 9) gave a yield of only 9%. An
improved yield might be achieved under amended reac-
tion conditions, but such studies have not been
conducted.
(
(
3×20 mL). The ether extract was washed with water
3×4 mL), dried over anhydrous sodium sulfate, and
In conclusion, a simple method for the transformation
of aromatic nitriles to the corresponding aldehydes
is described herein. The reaction can be carried
out under mild conditions and proceeds with good
to excellent yield. This method may find application
in multi-step organic synthesis of complex com-
pounds.
concentrated under reduced pressure to afford crude
product with above 90% purity. Purification of the
crude product by a silica gel chromatographic column
with a mixed solvent of methylene chloride and
methanol (95:5) gave a colorless liquid product.
Scheme 1. Proposed pathway of reduction of nitrile to aldehyde.
*
0
Corresponding author: Tel.: 240-632-4605; fax: 240-632-4148; e-mail: xif@medimmune.com
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00027-8

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F. Xi et al. / Tetrahedron Letters 43 (2002) 1395–1396
Table 1. Reaction time and yields of products
Acknowledgements
3. Miller, A. E. G.; Biss, J. W.; Schwartzaman, L. H. J.
Org. Chem. 1959, 24, 627–630.
The authors thank Dr. Gail Folena-Wasserman for
support of the work, and Dr. Jose Casas-Finet for
review of the manuscript.
4. Backeberg, O. G.; Staskun, B. J. Chem. Soc. 1962,
2961–2963.
5. Staskun, B.; Backeberg, O. G. J. Chem. Soc. 1964,
5
880–5881.
. van Es, T.; Staskun, B. J. Chem. Soc. 1965, 5775–5777.
7. Larock, R. C. Comprehensive Organic Transformations,
nd ed.; 1999; pp. 1271–1272.
6
References
2
1
2
. Stephen, H. J. Chem. Soc. 1925, 127, 1874–1877.
. Brown, H. C.; Grag, C. P. J. Am. Chem. Soc. 1964, 86,
8. Schwabe, K. Z. Elektrochem. 1957, 61, 744–752.
9. van Es, T.; Staskun, B. Org. Synth., Coll. Vol. 6, 1988,
631.
1085–1089.