Synthesis of aromatic aldehydes via NiCl2 reduction and hydrolysis of oxazolines

Article abstract of DOI:10.1016/j.tetlet.2004.07.119

Reduction of 2-aryl-oxazolines with NiCl₂/NaBH₄ followed by hydrolysis gives the corresponding aldehydes in good yields. Reduction of 2-aryl-oxazolines with NiCl₂/NaBH₄ followed by hydrolysis gives the correspon

Full text of DOI:10.1016/j.tetlet.2004.07.119

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7969–7970
Synthesis of aromatic aldehydes via NiCl2 reduction and
hydrolysis of oxazolines
M. Suresh Babu and K. M. Lokanatha Rai*
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India
Received 21 April 2004; revised 14 July 2004; accepted 23 July 2004
Available online 11 September 2004
Abstract—Reduction of 2-aryl-oxazolines with NiCl2/NaBH4 followed by hydrolysis gives the corresponding aldehydes in good
yields.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
NiCl2/NaBH4 for the conversion of carboxylic acids
to the corresponding aldehydes via oxazoline ring
formation.
Undoubtedly, the aldehyde functionality occupies a cen-
tral position in synthesis being able not only to accept
electrophiles but also to have reversed polarity (umpo-
lung) after derivatisation as a cyanohydrin, dithioacetal,
dithiane or a-aminonitrile derivative.1 It is not surpris-
ing therefore, that a large number of procedures2 have
been introduced to generate this functionality ranging
from oxidation of functional groups such as alcohols,
ethers, halides and alkenes or reduction of carboxylic
acids and their derivatives. Of these, the direct reduction
of a carboxylic acid to an aldehyde is difficult to achieve.
Different reagents, which have been used for this trans-
formation are lithium in dimethylamine,3 thexyl
borane,4 2-thiazoline-2-thiol,5 iso-butylmagnesium bro-
mide/dichloro bis(n-cyclopentadienyltitanium),6 bis(4-
methylpiperazinyl)aluminium hydride,7 etc. In addition,
a number of procedures are known for the reduction of
carboxylic acids to the corresponding aldehydes, includ-
ing reduction with thexylchloroborane–methyl sulfide,8
lithium aluminum hydride reduction to the primary
alcohol followed by reoxidation to the aldehyde, prepa-
ration of various acid derivatives followed by reduction
with Dibal-H,9 cyclic dialkyldiaminoaluminium
hydride,10 dichlorobis(cyclopentadienyl)titanium-cata-
lysed Grignard reactions8 all of which need laborious
work-up and further isolation of the product. This
prompted us to use the simple easily available reagent,
Benzoic acid was converted into the corresponding
oxazoline using a literature method.11 The oxazoline
was treated with NiCl2/NaBH4 at À10°C followed by
hydrolysis with 5% aq HCl to give the corresponding
aldehyde in 90% yield. This encouraging result
prompted us to study some other commercially available
aromatic acids and indeed excellent yields of the corre-
sponding aldehydes were obtained (Table 1). Unfortu-
nately reduction of the oxazoline derived from
propanoic acid under identical conditions gave only a
very low yield of propanal. All the products prepared
were identical by bp or mp and by IR and NMR spectro-
scopy with known aldehydes.12
2. General procedure for the preparation of
benzaldehyde from benzoic acid
In the first step of the reaction, 2-phenyl-2-oxazoline
(5mmol, 0.735g) and NiCl2 (2.37g, 10mmol) were taken
in methanol and cooled to À10°C. Sodium borohydride
(0.74g, 20mmol) was added in small amounts over
30min whilst maintaining the temperature at À10°C.
The mixture was then kept at 10°C for a further
30min to complete the reaction. The reaction mixture
was filtered through Celite and the solvent evaporated
under vacuum. The residue was treated with 5% HCl
(10mL) at 40°C for 10–15min, then cooled to room
temperature and extracted with diethyl ether (25mL).
*
Corresponding author. E-mail: kmlrai@eth.net
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.119

7970
M. Suresh Babu, K. M. Lokanatha Rai / Tetrahedron Letters 45 (2004) 7969–7970
Table 1.
N
NH2
OH
i. NiCl2/NaBH4
ii. Hydrolysis
+
ArCHO
Ar
O
a) Ar=C6H5; b) Ar=p-CH3-C6H4; c) Ar=p-CH3O-C6H4; d) Ar=3,4-(CH3O)2C6H3;
e) Ar=p-Cl-C6H4; f) Ar=m-Br-C6H4; g) Ar=o-NO2-C6H4; h) Ar=p-Me2N-C6H4;
Entry
Oxazoline
Aldehyde
Bp/Mp (°C)
Yield(%)
Found
Reported12
1
2
3
4
5
6
7
8
a
b
c
Benzaldehyde
m-Tolualdehyde
178–179
197–198
247–248
284–285
213–214
233–234
44–45
179
199
248
285
214
234
44
90
89
91
92
88
89
90
87
Anisaldehyde
Veratraldehyde
d
e
p-Chlorobenzaldehyde
m-Bromobenzaldehyde
o-Nitrobenzaldehyde
p-Dimethylamino benzaldehyde
f
g
h
73–74
74
5. Nagao, Y.; Kawabata, K.; Senio, K.; Fimota, E. J. Chem.
Soc., Perkin Trans. 1 1980, 1, 2470–2473.
6. Sato, F.; Jinbo, T.; Sato, M. Synthesis 1981, 871.
7. Muraki, M.; Mukaiyama, T. Chem. Lett. 1974, 12,
1447–1450.
The organic layer was washed with water, dried over
anhydrous sodium sulfate and evaporated under vac-
uum to give benzaldehyde as a colourless oily liquid in
90% yield (0.477g).
8. Brown, H. C.; Cha, J. S.; Yoon, N. M.; Nazer, B. J. Org.
Chem. 1987, 52, 5400–5406.
9. Chandrasekhar, S.; Suresh Kumar, M.; Muralidhar, B.
Tetrahedron Lett. 1998, 39, 909–910.
References and notes
10. Cha, J. S.; Moon, S. J. Bull. Korean Chem. Soc. 2002, 23,
1340–1342.
1. Hassner, A.; Rai, K. M. L. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon, 1991; Vol. 1, pp
541–577.
2. Larock, R. C. Comprehensive Organic Transformations;
VCH: New York, 1989.
3. Bedenbangh, A. O.; Bedenbangh, J. H.; Bergin, W. A.;
Adkins, J. D. J. Am. Chem. Soc. 1970, 92, 5774–5775.
4. Brown, H. C.; Heim, P.; Yoon, N. Y. J. Org. Chem. 1972,
37, 2942–2950.
11. Wiley, R. H.; Bennett, L. L., Jr. Chem. Rev. 1949, 44,
447–476 [Refluxing hydroxyamides (ArCONHCH2CH2-
OH) with SOCl2 followed by treatment with Na2CO3 gave
the oxazolines derivatives in typically 65% overall yield;
Fry E. M. J. Org. Chem. 1949, 14, 887–894].
12. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.;
Tatchell, A. R. In Vogel’s Text Book of Practical Organic
Chemistry, 5th ed.; 1994; pp 1334–1335.