Mendeleev
Communications
Mendeleev Commun., 2007, 17, 51
Synthesis of substituted 2-hydroxyaryl aldehydes
by the microwave-induced Reimer–Tiemann reaction
Yeshwant B. Vibhute,* Subhash M. Lonkar, Mudassar A. Sayyed and Mohammad A. Baseer
P. G. Department of Chemistry, Yeshwant College, Nanded 431602, India. E-mail: drybvibhute@yahoo.com
DOI: 10.1016/j.mencom.2007.01.020
A manipulatively simple and rapid method for the synthesis of substituted 2-hydroxy arylaldehydes by the Reimer–Tiemann
reaction under microwave irradiation is described.
2-Hydroxyaryl aldehydes are useful intermediates in the syn-
thesis of biologically active coumarins, chalcones, flavones,
flavanones, flavanols and Schiff bases, as well as heterocycles
like pyrazolines, pyrimidines, 1,5-benzothiazepines, 2-azeti-
dinones and 4-thiazolidinones. We report herein a very simple,
fast and general procedure for the formylation of substituted
phenols using aqueous alcoholic sodium hydroxide and chloro-
form under microwave irradiation, which leads to corresponding
2-hydroxyaryl aldehydes. The reactions were normally completed
within 25 min without steam distillation, and the yield was
improved as compared to a conventional method.1,2
References
1 Vogel’s Textbook of Practical Organic Chemistry, 4th edn., Longman,
London, 1978, p. 761.
2 A. H. Blatt, Org. Synth. Coll., 1955, 3, 463.
3 R. N. Sen and S. K. Ray, J. Indian Chem. Soc., 1932, 9, 173.
4 O. S. Kemp, J. Org. Chem., 1971, 36, 202.
5 B. Auwers, Ber., 1904, 37, 3934.
6 J. Haruhawa and H. Ishihawa, J. Pharm. Soc. Jpn., 1950, 70, 338.
7 S. S. Mokle, B. S. Dawane, M. A. Sayyed and Y. B. Vibhute, J. Chem.
Res., 2006, 101.
For the synthesis of 2-hydroxyaryl aldehyde by the Reimer–
Tiemann reaction according to a normal method, a mixture of
phenol, aqueous sodium hydroxide and chloroform was heated
at 60–70 °C for 45 min and then for 1 h by keeping in a boiling
water bath for completion of the reaction. Then, an excess
of chloroform from alkaline solution was removed by steam
distillation. The reaction mixture was cooled, acidified and
steam distilled to get 2-hydroxyaryl aldehyde in the distillate in
33% yield.
However, when the reaction was carried out under micro-
wave activation, 2-hydroxyaryl aldehydes 2 were obtained in
50–60% yields (Scheme 1).† The structures of the synthesised
aldehydes were confirmed by their melting points and spectral
data (1H NMR). The products were pure and further purification
was not needed. The time required was very short (25 min) as
compared to a normal method (4 h), and the energy efficiency
was increased.
Received: 12th July 2006; Com. 06/2751
†
Melting points (uncorrected) were determined in open capillary tubes.
The purity of compounds was checked by TLC using silica gel G. The
1H NMR spectra in CDCl3 were recorded on a Perkin-Elmer R-32 spectro-
meter using TMS as an internal standard.
General procedure for the synthesis of 5-chloro-2-hydroxyaryl aldehyde
2a. A mixture of 4-chlorophenol 1a (0.128 g, 1 mmol), dissolved in 8 ml
of an aqueous ethanolic (90:10 v/v) solution of sodium hydroxide (0.3 g,
7.5 mmol) and chloroform (0.24 g, 0.16 ml, 2 mmol) was taken in a
conical flask capped with a funnel. The flask was placed in a microwave
oven (450 W) and irradiated for 40 s six times (total 4 min) with short
intervals to avoid the evaporation of chloroform. The reaction mixture
was cooled and diluted with 15 ml of aqueous ethanol (90:10 v/v). The
solid was filtered off and washed with ethanol. Then, the solid was
dissolved in water and acidified using dilute hydrochloric acid to get
5-chloro-2-hydroxybenzaldehyde 2a.
For 2a: yield 52%, mp 98 °C (lit.,3 mp 100 °C). 1H NMR, d: 11.70 (s,
1H, OH), 9.92 (s, 1H, CHO), 6.87 (s, 1H, 3-HAr), 7.80 (s, 1H, 4-HAr),
7.62 (s, 1H, 6-HAr).
R
R
R1
R2
OH
R1
R2
OH
NaOH, [H2O:EtOH]
MWI
For 2b: yield 58%, mp 54 °C (lit.,4 mp 55 °C). H NMR, d: 11.80 (s,
1
+ CHCl3
1H, OH), 9.97 (s, 1H, CHO), 7.35 (s, 1H, 4-HAr), 6.96 (s, 1H, 5-HAr),
7.61 (s, 1H, 6-HAr).
CHO
For 2c: yield 60%, mp 103 °C (lit.,5 mp 105 °C). 1H NMR, d: 11.03 (s,
1H, OH), 9.92 (s, 1H, CHO), 6.86 (s, 1H, 3-HAr), 7.55 (s, 1H, 4-HAr),
7.85 (s, 1H, 6-HAr).
1a–g
2a–g
a R = R1 = H, R2 = Cl
b R = Cl, R1 = R2 = H
c R = R1 = H, R2 = Br
d R = R2 = Cl, R1 = H
e R = H, R1 = Me, R2 = Cl
f R = R1 = H, R2 = Ph
g R = R1 = R2 = H
1
For 2d: yield 52%, mp 93 °C. H NMR, d: 11.20 (s, 1H, OH), 10.01
(s, 1H, CHO), 7.65 (s, 1H, 4-HAr), 7.75 (s, 1H, 6-HAr).
For 2e: yield 57%, mp 79 °C. 1H NMR, d: 10.85 (s, 1H, OH), 9.95 (s,
1H, CHO), 7.50 (s, 1H, 3-HAr), 7.37 (s, 1H, 6-HAr), 2.30 (s, 1H, Me).
CHO
OH
OH
For 2f: yield 52%, mp 80 °C (lit.,6 mp 81 °C). H NMR, d: 10.85 (s,
1
NaOH, [H2O:EtOH]
+ CHCl3
1H, OH), 9.85 (s, 1H, CHO), 6.87 (s, 1H, 3-HAr), 7.50 (s, 1H, 6-HAr).
For 2g: yield 62%, bp 197 °C (lit.,1,7 bp 197 °C). 1H NMR, d: 11.12 (s,
1H, OH), 9.88 (s, 1H, CHO), 6.92–7.64 (s, 4H, HAr).
MWI
1h
2h
Scheme 1
The synthesis of 2-hydroxynaphthalene-1-carbaldehyde 2h was per-
formed by the above procedure using 8 ml of 40% aqueous ethanol
(40:60 v/v) from 2-naphthol. Yield 65%, mp 80 °C (lit.,1,7 mp 81 °C).
1H NMR, d: 13.02 (s, 1H, OH), 10.69 (s, 1H, CHO), 7.08 (s, 1H, 3-HAr),
7.90 (s, 1H, 4-HAr), 7.73 (s, 1H, 5-HAr), 7.41 (s, 1H, 6-HAr), 7.59 (s, 1H,
7-HAr), 8.25 (s, 1H, 8-HAr).
We are grateful to UGC, New Delhi, India for sanctioning Major
Research Grant and the Director, IICT, Hyderabad for providing
spectral data. We are also grateful to Dr. N.V. Kalyankar for
providing laboratory facilities.
– 51 –
Vibhute, Yeshwant B.
