TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2723–2725
One-pot transformation of nitriles into aldehyde tosylhydrazones
Marietta To´th and La´szlo´ Somsa´k*
Department of Organic Chemistry, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary
Received 6 December 2000; accepted 7 February 2001
Abstract—Reduction of various nitriles with Raney nickel and sodium hypophosphite in aqueous acetic acid and pyridine in the
presence of tosylhydrazine gave the corresponding aldehyde tosylhydrazones in good yield. © 2001 Elsevier Science Ltd. All rights
reserved.
Hydrazones are readily available compounds which can
be transformed into a large variety of other structures,
and have many industrial and biological applications.1
Tosylhydrazones are a similarly valuable subclass of
hydrazones whose most important synthetic uses are (a)
nucleophilic additions to the CꢀN double bond; (b)
electrophilic additions to hydrazone derived azaeno-
lates; (c) Bamford–Stevens and Shapiro reactions, and
(d) reductions, just to mention a few.2 The most widely
applied general method to obtain hydrazone derivatives
is the condensation of an aldehyde or ketone with an
(un)substituted hydrazine in the presence of an acidic
catalyst. With acid sensitive aldehydes this condensa-
tion can be performed under neutral conditions as
well.1 Carboxylic acid derivatives such as imino-esters
and orthoesters were also converted to hydrazones.1
from the imidazolidine by acid catalyzed hydrolysis.4,5
To the best of our knowledge this procedure was not
used with any other nitriles.
Since the above sequence also seemed lengthy with
respect to the planned tosylhydrazone synthesis, we
investigated a modification based on the following rea-
soning. The position of the equilibrium in hydrazone
forming reactions is known to be shifted well to the
product side.7 This might allow an aldehyde to be
trapped in situ by a hydrazine derivative similar to the
above mentioned case. Therefore, the reduction of vari-
ous nitriles 1 was investigated in the presence of tosyl-
hydrazine. These experiments proved that our
hypothesis was right, and the corresponding aldehyde
tosylhydrazones† 2 were isolated in good yield (Table
1). The transformation could be performed in the pres-
ence of various functional groups and was extended to
In the course of a project on the synthesis of gly-
comimetics we needed tosylhydrazones of 2,6-anhydro-
aldoses (C-glycopyranosyl aldehydes). Although several
syntheses were published for such aldehydes,3 these
compounds are still not readily accessible because of
the lengthiness of the preparative procedures. The most
straightforward way to get C-glycosyl aldehydes is
reduction of the easily available glycosyl cyanides with
Raney nickel–sodium hypophosphite in aqueous acetic
acid and pyridine.4,5 However, under these conditions
the product must be trapped as an imidazolidine
derivative by 1,2-dianilino-ethane, otherwise, in the
absence of this auxiliary, subsequent elimination of
acetic acid results in a 2,6-anhydro-ald-2-enose (1-for-
myl glycal).6 The aldehyde function can be unmasked
the per-O-acetylated-b-
-glucopyranosyl cyanide8 1h as
D
well. Several experiments were carried out with
aliphatic nitriles (such as acetonitrile, propionitrile, 4-
chlorobutyronitrile, ethyl cyanoacetate). In these cases
clean transformations could be detected by TLC, how-
† General procedure for the synthesis of aldehyde tosylhydrazones 2:
Raney nickel (1.5 g, from an aqueous suspension, Merck) was
added at room temperature to a vigorously stirred solution of
pyridine (5.7 mL), acetic acid (3.4 mL), and water (3.4 mL). Then
sodium hypophosphite (0.74 g, 8.4 mmol), tosylhydrazine (0.32 g,
1.7 mmol), and the corresponding nitrile 1 (1 mmol) were added to
the mixture. When the reaction was complete (TLC, eluent: ethyl
acetate–hexane 1:1) the insoluble materials were filtered off with
suction, and washed with dichloromethane (10 mL). The organic
layer of the filtrate was separated, washed with cold water (2×3 mL)
and was concentrated under reduced pressure. Residual pyridine
was removed by repeated co-evaporations with toluene. The residue
was purified by crystallization or by column chromatography (elu-
ent: ethyl acetate–hexane 1:1 or 1:2) to give the title compounds.
Keywords: hydrazones; nitriles; reduction; sulfonyl compounds; trap-
ping reactions.
* Corresponding author. Tel.: +36-52-512-900/2348; fax: +36-52-453-
836; e-mail: somsak@tigris.klte.hu
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00223-4
Tóth, Marietta
