One-pot synthesis of substituted catechols from the corresponding phenols

Article abstract of DOI:10.1016/j.tetlet.2005.03.082

Phenols are converted to salicylaldehydes with paraformaldehyde, MgCl ₂-Et₃N in THF, and when subsequently treated with aqueous NaOH and H₂O₂ afford the corresponding catechols. The sequence is conveniently carried out as a one-pot procedure.

Full text of DOI:10.1016/j.tetlet.2005.03.082

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3357–3358
One-pot synthesis of substituted catechols from the
corresponding phenols
Trond Vidar Hansena,* and Lars Skattebølb
aSchool of Pharmacy, Department of Chemistry, University of Oslo, PO Box 1068, Blindern, N-0316 Oslo, Norway
bDepartment of Chemistry, University of Oslo, PO Box 1033, Blindern, N-0315 Oslo, Norway
Received 31 January 2005;revised 8 March 2005;accepted 15 March 2005
Available online 5 April 2005
Abstract—Phenols are converted to salicylaldehydes with paraformaldehyde, MgCl2–Et3N in THF, and when subsequently treated
with aqueous NaOH and H2O2 afford the corresponding catechols. The sequence is conveniently carried out as a one-pot procedure.
Ó 2005 Elsevier Ltd. All rights reserved.
The catechol structural entity is present in a number of
important naturally occurring compounds and in other
molecules with interesting biological activity. Hence syn-
thetic methods leading to substituted catechols are of
considerable interest. Several methods of preparation
are known.1 The copper ion catalyzed substitution of
2-halophenols with hydroxide can lead to the corre-
sponding catechols in good yields, but the conditions
are quite harsh.2 The most versatile methods are prob-
ably the oxidation of salicylaldehydes or acetophenone
derivatives with either hydrogen peroxide or peracids,
the Dakin and Bayer–Villiger reactions, respectively.3,4
In the last two decades fermentation methods have been
introduced with considerable success.5 Benzene deriva-
tives are converted to the corresponding optically pure
cyclohexadiene-1,2-diols, which are readily transformed
into catechols. In the present paper we describe an effi-
cient one-pot method for the conversion of phenols to
catechols.
We recently described a simple procedure for the selec-
tive ortho-formylation of phenols that involves heating
a mixture of the phenol, anhydrous MgCl2, triethyl-
amine, and paraformaldehyde under reflux in acetoni-
trile or THF. For alkyl and halogen substituted
phenols excellent yields of salicylaldehydes were ob-
tained.6 Moreover, we have shown that the reaction
products from this formylation reaction can, without
isolation, be reacted with (+)-(R,R)-1,2-diammoniumcy-
clohexane mono-(+)-tartrate salt, thus giving rise to a
convenient high yielding and one-pot method for the
preparation of salen ligands.7 A similar approach
seemed feasible for the preparation of catechols;the
formylation reaction is followed by the Dakin oxidation
with H2O2 as a one-pot procedure (Scheme 1).
Accordingly, to the THF solution from the formylation
reaction, aqueous NaOH was added followed by 30%
H2O2. After 4–8 h at room temperature the reaction
Scheme 1.
Keywords: ortho-Formylation of phenols;Dakin reaction;Substituted catechols.
*
Corresponding author. Tel.: +47 22857450;fax: +47 22855947;e-mail: t.v.hansen@farmasi.uio.no
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.082

3358
T. V. Hansen, L. Skattebøl / Tetrahedron Letters 46 (2005) 3357–3358
2. For typical reaction conditions see: Allen, C. F. H.;
VanAllan, J. A. J. Org. Chem. 1949, 14, 798–801.
3. Surrey, A. R. Org. Synth. 1946, 26, 90–92.
4. (a) Hue, R.;Jubier, A.;Andrieux, J.;Resplandy, A.
Bull.
¨
Soc. Chim. Fr. 1970, 3617–3624;(b) Hassall, C. H. Org.
React. 1957, 9, 73–106.
5. (a) Bui, V. P.;Hudlicky, T.;Hansen, T. V.;Stenstrøm, Y.
Tetrahedron Lett. 2002, 43, 2839–2841;(b) Endoma, M. A.;
Bui, V. P.;Hansen, J.;Hudlicky, T. Org. Process Res. Dev.
2002, 6, 525–532;(c) Bui, V. P.;Hansen, T. V.;Stenstrøm,
Y.;Hudlicky, T. Green Chem. 2000, 2, 263–265, and
references cited therein.
6. Hofsløkken, N. U.;Skattebøl, L. Acta Chem. Scand. 1999,
53, 258–262.
7. Hansen, T. V.;Skattebøl, L. Tetrahedron Lett. 2005, 46, in
press.
8. (a) Pearson, D. E.;Wysong, R. D.;Breder, C. V. J. Org.
Chem. 1967, 32, 2358–2360;(b) Lorraine, M. D.;Brazwell,
E. M.;Vander-Jagt, D. L.;Royer, R. E. Org. Prep. Proc.
Int. 1990, 22, 495–500;(c) Klix, R. C.;Chain, M. H.;
Bhatia, A. V. Tetrahedron Lett. 1995, 36, 6413–6414.
9. Preparation of 3: A mixture of 2-bromophenol (1.73 g,
10 mmol), MgCl2 (1.90 g, 20 mmol), Et3N (2.02 g,
20 mmol) and paraformaldehyde (0.90 g, 30 mmol) under
argon and in THF (15 mL) was heated under reflux for 3 h.
The reaction mixture was cooled to room temperature and
sodium hydroxide (0.05 N, 30 mL) was added dropwise.
When all components had dissolved, H2O2 (30%, 4 mL) was
added dropwise. After 2 h, another portion of 30% H2O2
(4 mL) was added and the reaction mixture was stirred for
4 h until complete conversion (TLC). The reaction mixture
was acidified (1.0 N HCl, 25 mL) and extracted with
CH2Cl2. The extract was washed with NaS2O4, the solvent
removed under reduced pressure and the residue dissolved
in a small amount of MeOH. Filtration and washing
(CH2Cl2, 50 mL) through a plug of silica followed by
evaporation of the solvent gave a solid residue, that was
recrystallized from pentane to give 3-bromocatechol 3 as
white crystals (1.03 g, 55%): mp 40–41 °C, lit.8a mp 40.5–
41.5 °C; 1H NMR (300 MHz, CDCl3): d 5.65 (bs, 2H), 6.72
(t, J = 7.8 Hz, 1H), 6.85 (dd, J = 1.5, 7.8 Hz, 1H), 6.98 (dd,
J = 1.5, 7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3): d 109.5,
114.9, 121.9, 123.3, 140.3, 144.6;HRMS calcd for
C6H5BrO2 (M+): 187.9473, found 187.9485.
Figure 1.
was complete and normal work-up furnished the crystal-
line catechol derivative. The reactions were carried out
with both 2- and 4-substituted phenols as starting mate-
rials. The catechols 1–8, prepared by this method, are
shown in Figure 1. Except for compound 3, they are
all commercially available compounds that were identi-
fied by comparison with authentic samples.8 The re-
corded yields are for recrystallized materials, based on
the phenols, and are not optimized. Experimental details
for the preparation of 3 are given below and are typical.9
Substituted phenols are readily available, and the pres-
ent method appears to be a convenient way of trans-
forming them into the corresponding catechols.
References and notes
1. Muller, E. In Houben-Weyl: Methoden der Organischen
¨
Chemie;Bayer, O., Ed.;Georg Thieme: Stuttgart, 1976;
Vol. VI/1c, 1, pp 166–308.