Microwave assisted McFadyen-Stevens and Huang-Minlon reactions

Article abstract of DOI:10.1081/SCC-120005941

Microwave irradiation has been employed in McFadyen-Stevens reaction to convert p-toluenesulfonyl hydrazides 1 to the aldehydes 2. Also, microwave has been applied in Huang-Minlon reduction of carbonyl compounds 3 to the corresponding hydrocarbons 4.

Full text of DOI:10.1081/SCC-120005941

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MICROWAVE ASSISTED McFADYEN–STEVENS AND
HUANG–MINLON REACTIONS
Parasuraman Jaisankar a , Bikash Pal a & Venkatachalam Sesha Giri b
a Department of Medicinal Chemistry, Indian Institute of Chemical Biology, 4, Raja S. C.
Mullick Road, Jadavpur, Calcutta, 700 032, India
b Department of Medicinal Chemistry, Indian Institute of Chemical Biology, 4, Raja S. C.
Mullick Road, Jadavpur, Calcutta, 700 032, India
Published online: 16 Aug 2006.
To cite this article: Parasuraman Jaisankar , Bikash Pal & Venkatachalam Sesha Giri (2002): MICROWAVE ASSISTED
McFADYEN–STEVENS AND HUANG–MINLON REACTIONS, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:16, 2569-2573
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 16, pp. 2569–2573, 2002
MICROWAVE ASSISTED MCFADYEN–
STEVENS AND HUANG–MINLON
REACTIONS
Parasuraman Jaisankar, Bikash Pal,
*
and Venkatachalam Sesha Giri
Department of Medicinal Chemistry, Indian Institute of
Chemical Biology, 4, Raja S. C. Mullick Road,
Jadavpur, Calcutta—700 032, India
ABSTRACT
Microwave irradiation has been employed in McFadyen–
Stevens reaction to convert p-toluenesulfonyl hydrazides 1
to the aldehydes 2. Also, microwave has been applied in
Huang–Minlon reduction of carbonyl compounds 3 to the
corresponding hydrocarbons 4.
Key Words: Microwave; Reduction; McFadyen-Stevens;
Huang-Minlon; Nauclefidine
Microwave heating has been employed as a frequent resource for
improvement of classical reactions, and sometimes it led to discover new
reactions. In the last few years there has been a growing interest in the use of
microwave heating in organic synthesis. The use of such non-conventional
*Corresponding author. Fax: þ91-33-4735197/4730284; E-mail: vsgiri@iicb.res.in
2569
DOI: 10.1081/SCC-120005941
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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2570
JAISANKAR, PAL, AND GIRI
Scheme 1.
reaction conditions reveals several features like: a short reaction time com-
pared to conventional heating, ease of work-up after a reaction, reduction in
the usual thermal degradation and better selectivity.[1]
McFadyen–Stevens[2] aldehyde synthesis is a well-known reaction used
for the reduction of carboxylic acids to the corresponding aldehydes via
their arylsulfonhydrazides. Earlier, in the course of synthesizing the alkaloid
nauclefidine, McFadyen–Stevens reaction was used by us.[3] Now we had
applied this reaction but under microwave condition to successfully synthe-
size the same alkaloid 2d in excellent yield from the corresponding tosylhy-
drazide (1d). The microwave conditions for the McFadyen–Stevens reaction
(Scheme 1) have been generalized and the results are summarized in Table 1.
Although, Sandu et al.[4] have employed the well-known Wolff–
Kishner[5] reduction under microwave conditions but then it is a two step
process. Earlier, we had employed Huang–Minlon reduction, a modification
of Wolff–Kishner reduction for converting the compound 3a to 4a, which
is an important intermediate in the synthesis of the alkaloid flavopereirine,
a cancer cell inhibiting alkaloid.[6]
We have now obtained the same intermediate 4a from 3a with Huang–
Minlon reduction but under microwave conditions (Scheme 2) with excellent
yield. The procedure has been generalized and the results are summarized
in Table 2.
We have observed that in the case of aromatic aldehydes and ketones
the reaction is influenced by the substituents in the ortho, para or meta
position of the carbonyl functionality. 3-Acetyl pyrrole on Huang–Minlon
reduction under microwave irradiation undergoes deacetylation to afford
pyrrole, a phenomenon earlier reported by us for similar systems under
microwave free conditions.[7]
All the products in both the reactions have been identified by compar-
ison with authentic samples. Both McFadyen–Stevens and Huang–Minlon
reactions require high temperature. We have utilised these reactions under
microwave conditions in the synthesis of the alkaloids nauclefidine and
flavopereirine respectively. In summary, we have achieved a simple and
efficient procedure for the above two important reactions.

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MCFADYEN–STEVENS AND HUANG–MINLON REACTIONS
2571
Table 1.
Starting
Material (1)
Reaction
Time (Watt)
Product (2)
(Yield)
3 Â 1/2 min (650 W)
a
2 Â 1 min (250 W)
3 Â 1/2 min (350 W)
b
5 Â 1 min (350 W)
c
d
6 Â 1 min (450 w)
Scheme 2.

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2572
JAISANKAR, PAL, AND GIRI
Table 2.
Starting
Material (3)
Product (4)
(Yield)
Reaction Time
2 Â 1 min 2 Â 1 min
a
b
c
2 Â 1 min 3 Â 1 min
(1 Â 1 min at 450 W)
2 Â 1 min 3 Â 1 min
2 Â 1 min 2 Â 1 min
d
e
2 Â 1 min 2 Â 1 min
EXPERIMENTAL
Melting points were determined in open capillaries and are uncor-
rected. NMR spectra were measured on a Bruker 300 MHz spectrometer
using TMS as internal standard. Compounds 1 were prepared following
the reported[3] procedure. The reactions were performed in a commercial
microwave oven of 1000 W capacity. For oils and low melting solids the
irradiation has to be done at a lower wattage (150 W) to begin with and
then, it is further irradiated at higher wattage (250–350 W) in the same
reaction flask.

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MCFADYEN–STEVENS AND HUANG–MINLON REACTIONS
2573
General Procedure for McFadyen–Stevens Aldehyde Synthesis: A mix-
ture of the p-toluenesulfonyl acid hydrazide 1 (2 mmol), Na2CO3 (2.2 mmol),
and powdered glass (500 mg) in ethylene glycol (5 mL) was taken in an
Erlenmeyer flask. The reaction flask was placed in a commercial microwave
oven of 1000 W capacity. The reaction mixture was initially irradiated
at 150 W for a couple of minutes and then at 250–650 W for 1–6 min (mon-
itored by tlc). The reaction mixture was cooled to room temperature,
neutralised and then extracted with chloroform. The extract was dried
over Na2SO4, evaporated, and then column chromatography over silica
gel afforded the corresponding aldehydes in reasonable yield.
General Procedure for Huang–Minlon Reduction: In a typical example,
a mixture of the ketone/aldehyde 3 (2 mmol) hydrazine hydrate (4 mmol,
200 mg) and powdered KOH (5 pellets) was taken in an Erlenmeyer flask.
The reaction flask was placed in a commercial microwave oven of 1000 W
capacity. The reaction mixture was initially irradiated at 150 W for a couple
of minutes and then at 250–350 W for 1–5 min (monitoring by tlc). The
reaction mixture was cooled to room temperature, neutralised and then
extracted with chloroform. The extract was dried over Na2SO4, evaporated,
and then column chromatography over silica gel afforded the corresponding
hydrocarbon in reasonable yield.
REFERENCES
1. (a). Mingos, D.M.; Baghurst, D.R. Chem. Soc. Rev. 1991, 20, 1; (b).
Langa, F.; Cruz, P.L.; Hoz, A.D.L.; Diaz-Ortiz, A.; Diez-Barra, E.
Contemporary Org. Synthesis 1997, 4, 373, and the references cited
therein; (c). Bogdal, D. Wiad. Chem. 1999, 53, 66; (d). Bentiss, F.;
Lagrenee, M.; Barbry, D. Tetrahedron Lett. 2000, 41, 1539, and the
references cited therein.
2. (a). McFadyen, J.S.; Stevens, T.S. J. Chem. Soc. 1936, 584; (b) Dudman,
C.C.; Grice, P.; Reese, C.B. Tetrahedron Lett. 1980, 21, 4645.
3. Manna, R.K.; Jaisankar, P.; Giri, V.S. Synthetic Commun. 1998, 28, 9.
4. Gadhwal, S.; Baruah, M.; Sandhu, J.S. Synlett. 1999, 1573.
5. Todd, D. Org. Reactions 1948, 4, 378.
6. Giri, V.S.; Maiti, B.C.; Pakrashi, S.C. Heterocycles 1984, 22, 233.
7. Giri, V.S.; Maiti, B.C.; Pakrashi, S.C. Heterocycles 1985, 23, 71.
Received in the UK June 15, 2001

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