BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
quantitatively (entries 7 and 8, Table 2). Aliphatic substrates
(entries 9 and 10, Table 2) were also smoothly reduced to
the corresponding aldehydes in quantitative yields. The above
results demonstrate the broad scope of the reaction in terms of
the substituent on the tertiary amides.
a representative example of the partial reduction of
N,N-dimethylbenzamide to benzaldehyde. A dry and argon-
flushed flask, equipped with a magnetic stirring bar and a sep-
tum, was charged with N,N-dimethylbenzamide (0.07 mL,
0.5 mmol) and THF (5 mL). After cooling to 0 ꢀC, piperi-
dine-modified Red-Al (2.5 mL, 0.4 M 1.0 mmol) was added
dropwise and the mixture was stirred for 30 min at room tem-
perature. The reaction was quenched with 1 N aqueous HCl
(5 mL) and the product was extracted with diethyl ether
(10 mL). The organic layer was dried over anhydrous magne-
sium sulfate. GC analysis showed quantitative conversion to
benzaldehyde. All products listed in Table 2 were confirmed
through comparison with the GC data of authentic samples.
In conclusion, we developed a convenient alternative
method for the synthesis of aldehydes from representative ter-
tiary amides with almost quantitative yields using a new piper-
idine-modified Red-Al agent, which was easily prepared by
reacting commercially available Red-Al with piperidine.
The present methodology is the first systematic and general
study of the partial reduction of tertiary amides to aldehydes
using modified Red-Al reducing agents. This method has
the following advantages: almost quantitative product yields,
short reaction time, and convenient reaction temperature.
Therefore, we believe that the new piperidine-modified
Red-Al has immense potential and can be broadly applied
as an alternative partial reducing agent for the synthesis of
aldehydes from tertiary amides in organic synthesis.
Acknowledgments. This study was supported by the
National Research Foundation of Korea Grant funded by
the Korean Government (2014R1A1A2059124) and the
2014 Research Grant from Kangwon National University
(No. 120140289).
Experimental
References
General. All glassware were dried thoroughly in an oven,
assembled hot, and cooled under a stream of dry nitrogen prior
to use. All reactions and manipulation of air- and moisture-
sensitive materials were carried out using the standard techni-
ques for handling air-sensitive materials. All chemicals were
commercial reagents of the highest purity, which were further
purified by standard methods before use. Tetrahydrofuran
(THF) was dried over sodium-benzophenone and distilled.
GC (gas chromatography) analyses were performed on
a Yonglin (Anyang-si, South Korea), Acme 6000M FID
chromatograph using an HP-5 (5%-diphenyl-95%-dimethyl-
siloxane copolymer, 30 m) capillary column. All GC yields
were determined using a mixture of naphthalene as internal
standard and an authentic sample of the product.
Preparation of New Reducing Reagent (Piperidine-
modified Red-Al). A dry and argon-flushed flask, which
was equipped with a magnetic stirring bar and a septum,
was charged with piperidine (5.4 mL, 55 mmol) and 80 mL
THF. After cooling to 0 ꢀC, Red-Al (14.3 mL, 3.5M in tolu-
ene, 50 mmol) was added dropwise and stirred for 1 h at the
same temperature, which afforded a colorless homogeneous
solution. The concentration of the piperidine-modified Red-
Al solution in THF-toluene was measured gasometrically by
hydrolysis of an aliquot of the solution with aqueous 1
N HCl at 0 ꢀC.
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Partial Reduction of Tertiary Amides to Corresponding
Aldehydes. The following experimental procedure describes
Bull. Korean Chem. Soc. 2015, Vol. 36, 1919–1921
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim