Novel chemoselective reduction of aldehydes in the presence of other carbonyl moieties with thiourea dioxide

Article abstract of DOI:10.1080/00397910802026220

Reduction of a variety of aldehydes in the presence of other carbonyl moieties to the corresponding alcohols occurs chemoselectively in high yields upon treatment with inexpensive reagent thiourea dioxide (TUDO) in aqueous alkali-ethanolic system for 2 h at 90°C. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802026220

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Novel Chemoselective
Reduction of Aldehydes in the
Presence of Other Carbonyl
Moieties with Thiourea Dioxide
Shikha Sambher a b , Chinnappan Baskar b & Ranjit S.
Dhillon a
a Department of Chemistry , Punjab Agricultural
University , Ludhiana, Punjab, India
b Department of Chemistry , Lovely Professional
University , Phagwara, Punjab, India
Published online: 18 Aug 2008.
To cite this article: Shikha Sambher , Chinnappan Baskar & Ranjit S. Dhillon (2008)
Novel Chemoselective Reduction of Aldehydes in the Presence of Other Carbonyl
Moieties with Thiourea Dioxide, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 38:13, 2150-2157, DOI:
10.1080/00397910802026220
To link to this article: http://dx.doi.org/10.1080/00397910802026220
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Synthetic Communications1, 38: 2150–2157, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802026220
Novel Chemoselective Reduction of Aldehydes in
the Presence of Other Carbonyl Moieties with
Thiourea Dioxide
Shikha Sambher,1,2 Chinnappan Baskar,2 and Ranjit S. Dhillon1
1Department of Chemistry, Punjab Agricultural University,
Ludhiana, Punjab, India
2Department of Chemistry, Lovely Professional University,
Phagwara, Punjab, India
Abstract: Reduction of a variety of aldehydes in the presence of other carbonyl
moieties to the corresponding alcohols occurs chemoselectively in high yields
upon treatment with inexpensive reagent thiourea dioxide (TUDO) in aqueous
alkali–ethanolic system for 2 h at 90 ꢀC.
Keywords: Aldehyde; Carbonyl; Chemoselective; Formamidine sulfinic acid;
Reduction; Thiourea dioxide
Chemo-, stereo-, and regioselective reductions of carbonyl compounds to
the corresponding alcohols are some of the important functional group
conversions in organic synthesis.[1–5] A variety of regents have been
employed to achieve this transformation, namely NaBH4,[6–10] poly-
methylhydrosiloxane (PMHS),[11] sodium dithionate,[12,13] nickel
boride,[14] and so on. In contrast to these reagents, thiourea dioxide is
much less expensive and does not affect the environment.
Thiourea dioxide (TUDO) is a strong reductant that rearranges
under alkaline conditions to form formamidine sulfinic acid (FSA).[15]
Received August 7, 2007
Part of this work was presented at the IUPAC Second International Sym-
posium on Green=Sustainable Chemistry, University of Delhi, New Delhi, India,
January 10–13, 2006.
Address correspondence to Ranjit S. Dhillon, Department of Chemistry,
Punjab Agricultural University, Ludhiana 141004, Punjab, India. E-mail:
dhillonr@rediffmail.com
2150

Aldehyde Reduction with Thiourea Dioxide
2151
TUDO is a commercially available reducing agent[15] and has vast appli-
cations for waste paper processing,[16] wool bleaching,[17] the reduction of
ferredoxin, cytochrome C, and methemoglobin,[18] and inactivation and
modification of citidine triphosphate synthase.[19]
TUDO is also used for the reduction of organosulfur compounds
(sulfylimines, sulfoxides, disulfides),[20,21] the synthesis of selenides and
tellurides from the corresponding diselenides and ditellurides under
phase-transfer catalysis,[22,23] and the deoxygenation of a,b-epoxy
ketones,[24] and heteroatomic N-oxides.[25] Aromatic nitro, azoxy, azo
and hydrazo compounds were reduced to the corresponding amines
and quinones to hydroquinones with TUDO.[26]
Our research is mainly devoted to finding new procedures for chemo-
selective reduction of organic functionalities using inexpensive and green
reagents.[1,12,13, 27,28] In this article, we report a simple procedure for
chemoselective reduction of a variety of aldehydes in the presence of
other carbonyl moieties with thiourea dioxide (TUDO) in aqueous alkali–
ethanolic system at 90 ꢀC to the corresponding alcohols (Scheme 1),
where excellent discrimination between various types of carbonyl func-
tionality has been observed. The results are shown in Table 1.
In our initial studies, we have chemoselectively reduced benzaldehyde
over acetophenone with 1 equivalent of TUDO in an aqueous alkali–
ethanolic system at 90 ꢀC for 2 h. The chemoselectivity of the reduction
was perfect, and benzyl alcohol was obtained as the sole product besides
acetophenone as an intact material. The same reaction condition was
further examined with a pair of different aldehydes and ketones as shown
in Table 1. We observed that the aldehyde is reduced exclusively.
In the next attempt, we applied this protocol for the reduction of
other aldehydes such as substituted aromatic aldehyde and hexanal in
the presence of acetophenone, bezophenone, or 2-heptanone (entries
2–10); aldehydes were reduced in high chemoselectivity with high isolated
yields (83–89%). The usefulness of this reducing system was further
investigated with hexanal in the presence of other carbonyl moieties such
as ester and acid chloride (entries 11 and 12). Hexanal selectively reduced
to hexanol in high yields. This unique reactivity of this reducing agent
Scheme 1. Chemoselective reduction of aldehydes using thiourea dioxide
(TUDO)–NaOH–EtOH.

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2153

2154

Aldehyde Reduction with Thiourea Dioxide
2155
affords possibilities for achieving a selective reduction of aldehyde in the
presence of other carbonyl functionality in complex molecules.
In conclusion, TUDO in an aqueous alkali–ethanolic system can serve
as an efficient procedure for the chemoselective reduction of aldehydes in
the presence of other carbonyl moieties using less toxic and easily available
reagents. Further investigations on mechanistic aspects and synthetic
applications of this reaction are currently under way in our laboratory.
EXPERIMENTAL
General
All reagents were purchased from Sigma-Aldrich and SD Fine and were
used without further purification unless otherwise stated. Products were
characterized by comparison with authentic samples: mp=bp, mixed mp
(wherever applicable), IR, and NMR. All yields refer to isolated pure
products. Thin-layer chromatography (TLC) was applied for the purity
determination of substrates, products, and reaction monitoring over a
silica-gel glass plate.
General Procedure for Chemoselective Reduction of Aldehydes with
TUDO in an Aqueous Alkali–Ethanolic System
Aqueous NaOH (20 mmol) and solid thiourea dioxide (1.08 g, 10 mmol,
in one lot) were added to a stirred solution of aldehyde (10 mmol) and
ketone (10 mmol) in ethanol (30 mL). The mixture was stirred for 2 h at
90 ꢀC and cooled to room temperature, and ethanol was distilled off.
The aqueous layer was extracted with Et2O (3 Â 25 mL), dried (anhyd.
Na2SO4), and concentrated. The crude products were purified by column
chromatography on silica gel using a solvent mixture (EtOAc–hexane) to
get the corresponding pure primary alcohol in 83–89% yield (Table 1).
ACKNOWLEDGMENT
The authors thank University Grants Commission (UGC), New Delhi,
for financial support.
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