An unusual involvement of NaIO4 in the acetylation of bisphenol during attempted oxidative acetylation

Article abstract of DOI:10.1016/j.tetlet.2013.10.072

An unexpected behaviour of compilation of reagent sodium metaperiodate in acetic anhydride for acetylation of bisphenols was observed during attempted oxidative acetylation of bisphenols for the synthesis of a bis-acetoxy cyclohexadienone. The products we

Full text of DOI:10.1016/j.tetlet.2013.10.072

Tetrahedron Letters 54 (2013) 7053–7055
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An unusual involvement of NaIO4 in the acetylation of bisphenol
during attempted oxidative acetylation
⇑
Deepak Singh, Pradeep T. Deota
Department of Applied Chemistry, Faculty of Technology & Engineering, The Maharaja Sayajirao University of Baroda, Vadodara 390 001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An unexpected behaviour of compilation of reagent sodium metaperiodate in acetic anhydride for acet-
ylation of bisphenols was observed during attempted oxidative acetylation of bisphenols for the synthe-
sis of a bis-acetoxy cyclohexadienone. The products were characterized by their spectral and analytical
data and a probable mechanism for acetylation involving role of NaIO4 is proposed.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 16 September 2013
Revised 11 October 2013
Accepted 15 October 2013
Available online 23 October 2013
Keywords:
Bisphenols
Bis-cyclohexadienone
Oxidative acetylation
Acetylation
Bis-triquinane
The cyclohexadienone ketals, quinols and its congeners have
enormoussynthetic potentialfor the creationof molecularcomplex-
ity in a stereocontrolled manner.1 The use of cyclohexadienones as
buildingblockshas acceleratedthedevelopment of newmethodsto-
wards total syntheses of various polyquinanes and other families of
natural products.1,2 These natural products possess diverse chemical
behaviour and interesting biological profiles.1,2
Among the natural products triquinanes, a subset of rapidly
growing group of polyquinanes, have aroused worldwide interest
among organic chemists due to their fascinating molecular archi-
tecture and potent biological activity.2 As a result numerous syn-
thetic approaches have been developed for the construction of
triquinane natural products since their discovery.3
Recently in 2010 Opatz and co-workers have encountered the
six new triquinane sesquiterpenoids.4 Out of the six, two members
have a different type of molecular architecture composed of two
triquinane skeletons, recognized as bis-triquinanes. The presence
of two tricyclic frameworks with different functional groups and
stereochemical complexity has further enhanced the interest in
this family of compounds.
Literature records a number of methods for the synthesis of
cyclohexadienones by oxidation of phenols using a variety of
reagents.6a–d However there is no report on the synthesis of
bis-cyclohexadienone of type 1 excepting our own.7 Previously
we reported the synthesis of bis-cyclohexadienones by oxidative
acetylation of tetramethyl bisphenol-F using LTA in benzene.7 Dur-
ing the course of our work, it was found that the reaction of bisphe-
nol-F to bis-cyclohexadienone can also be accomplished in toluene
instead of benzene which is known for its carcinogenity.8 However
this method also has certain limitations for the oxidation of higher
members of bisphenols.
In the area of synthesis of acetoxy cyclohexadienone we have
previously reported the use of reagent NaIO4 in Ac2O for the
synthesis of various types of acetoxy cyclohexadienonesby oxida-
tive acetylation of structurally different phenols.9
In search of another method, we explored the use of reagent
NaIO4 in Ac2O for the synthesis of bis-acetoxy cyclohexadienones
by oxidative acetylation of bisphenols. Thus bisphenol 5 was trea-
ted with NaIO4 in Ac2O at 75 °C for 3 h, which furnished the novel
diacetates 10 rather than the expected bis-acetoxy cyclohexadie-
none 1512 (Scheme 2).
Inspired by the above report, we recently reported a novel
method for quick assembly of the basic bis-triquinane skeleton 4
from bis-cyclohexadienone 1 by Diels–Alder cycloaddition and
We then attempted the reaction of other bisphenols 6–9 under
the same reaction conditions using NaIO4 in Ac2O. In all the cases
only acylated products were obtained however no product from
oxidative acetylation was isolated12 (Scheme 2, Table 1).
Literature records numerous reports in which NaIO4 has been
employed for the oxidation of phenols to cyclohexadienones and
subsequent exploration towards the synthesis of a variety of
photochemical oxa-di-p
-methane rearrangement5 (Scheme 1).
⇑
Corresponding author. Tel.: +91 0265 2434188x415, 212; fax: +91 0265
2423898.
E-mail address: deotapt@yahoo.com (P.T. Deota).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.10.072

7054
D. Singh, P. T. Deota / Tetrahedron Letters 54 (2013) 7053–7055
OAc
OAc
OAc
O
O
O
O
OAc
O
O
O
OAc
AcO
O
OAc
AcO
1
2
3
4
Scheme 1. Preparation of bis-triquinane 4 from bis-cyclohexadienone 1.
OAc
HO
OH
AcO
OAc
O
O
NaIO4, Ac2O,
75 °C
OAc
R1
R1
R2
R1
R2
R2
10-14
15-19
5-9
Expected
Isolated
5) R1=CH3, R2=H; 6) R1=CH3CH2, R2=H; 7) R1=CH3CH2CH2, R2=H; 8) R1=R2=CH3; 9) R1,
R2= -(CH2)4-
Scheme 2. Acetylation of bisphenol during attempted synthesis of bis-cyclohexadienone using NaIO4 in Ac2O.
Table 1
Adler and Holmberg have first reported the syntheses of various
types of cyclohexadienones from a wide variety of phenols with
NaIO4.10 The spiroepoxy cyclohexadienones obtained by Adler oxi-
dation of o-hydroxy benzyl alcohol have tremendous synthetic
importance in the syntheses of triquinanes, ovalicin and other nat-
ural products11 (Scheme 3).
It was thought that the acetylation of phenol might be taking
place due to nucleophilic attack of phenolic OH on a carbonyl of
acetic anhydride without the involvement of NaIO4. To test this
hypothesis, bisphenol 5 was heated under reflux in Ac2O, however
the formation of acetylated product was not observed. This indi-
cated some role of NaIO4 in the acetyaltion of bisphenol.
Acetylation of bisphenols 5–9 using NaIO4 in Ac2O
Entry
Bisphenol
Diacetates
Time (h)
Yield (%)
1
2
3
4
5
5
6
7
8
9
10
11
12
13
14
3
88
87
87
84
88
3.5
3.5
4
4.5
natural products10,11 but there is no report for acetylation of phe-
nol in the presence of NaIO4.
O
O
O
OH
OH
Dimerization
NaIO4, H2O
O
O
O
20
21
Scheme 3. Oxidation of phenol using NaIO4.
22
O
O
CH3
CH3
Na
O
O
O
O
O
O
C
CH3
O
Na
I
+
H3C
O
O
IO3
23
24
25
O
IO3
O
H3C
O
26
AcO
-IO4
H
Ar
Ar
CH COO
R
Na
R'
3
R
R'
27
28
29
Scheme 4. Acetylation of bisphenols using NaIO4 in Ac2O.

D. Singh, P. T. Deota / Tetrahedron Letters 54 (2013) 7053–7055
7055
Table 2
2. (a) Mehta, G.; Srikrishna, A. Chem. Rev. 1997, 97, 671; (b) Liao, C. C.; Peddinti, R.
K. Acc. Chem. Res. 2002, 35, 856; (c) Coleman, R. S.; Grant, E. B. J. Am. Chem. Soc.
1995, 117, 10889.
3. Comer, F. W.; Trotter, J. J. Chem. Soc. Phys. Org. 1966, 1, 11.
4. Liermann, J. C.; Schuffler, A.; Wollinsky, B.; Birnbacher, J.; Kolshorn, H.; Anke,
T.; Opatz, T. J. Org. Chem. 2010, 75, 2955.
The acetylation of bisphenol 5 in Ac2O using different reagents
Entry
Reagent
Temp (°C)
Time (h)
Yield (%)
1
2
3
4
NaIO4
KIO4
CH3COONa
CH3COOH
75
75
120
118
3
88
90
82
80a
1.5
3.5
6
5. Singh, D.; Deota, P. T. Tetrahedron Lett. 2012, 53, 6527.
6. (a) Nemoto, T.; Ishige, Y.; Yoshida, M.; Kohno, Y.; Kanematsu, M.; Hamada, Y.
Org. Lett. 2010, 12, 5021; (b) Zbiral, E.; Wessely, F.; Lahrmann, E. Mh. Chem.
1960, 91, 331; (c) Barton, D. H. R.; Brewster, A. G.; Ley, S. V.; Reed, C. M.;
a
The reaction did not reach completion, yield is based on the recovery of starting
materials.
Rosenfeld, M. N. J. Chem. Soc., Perkin Trans.
1 1977, 567; (d) Drutu, I.;
Njardarson, J. T.; Wood, J. L. Org. Lett. 2002, 4, 493; (e) Singh, V.; Lahiri, S.; Kane,
V. K.; Stey, T.; Stalke, D. Org. Lett. 2003, 5, 2199.
7. Deota, P. T.; Parmar, H. S.; Valodkar, V. B.; Upadhaya, P. R.; Sahoo, S. P. Synth.
Commun. 2006, 36, 673.
8. Singh, D.; Deota, P. T. Synth. Comm. 2013, 43, 292.
We have proposed a probable mechanism for the formation of
the acetylated products of bisphenols (Scheme 4). Periodate per-
haps attacks first on the carbonyl carbon of the anhydride 24 to
generate sodium acetate 27 and ethanoylperiodate 26 via interme-
diate 25. The sodium acetate thus formed is a conjugate base which
initiates the nucleophilic reaction of bis-phenol 28 with etha-
noylperiodate 26 to give the acetylated product 29. Acetylation
of two hydroxyls in the bisphenol molecule may be synchronous
or stepwise.
9. Deota, P. T.; Upadhyay, P. R.; Parmar, H. S. Synth. Commun. 2005, 35, 1715.
10. (a) Adler, E.; Holmberg, K. Acta Chem. Scand. 1974, 28B, 465; (b) Adler, E.;
Junghahn, L.; Lindberg, U.; Berggren, B.; Westin, G. Acta Chem. Scand. 1960, 14,
1261; (c) Adler, E.; Brasen, S.; Miyake, H. Acta Chem. Scand. 1971, 25, 2055; (d)
Adler, E.; Dahlen, J.; Westin, G. Acta Chem. Scand. 1960, 14, 1580; (e) Adler, E.;
Falkehag, I.; Smith, B. Acta Chem. Scand. 1962, 16, 529.
11. (a) Corey, E. J.; Dittami, J. P. J. Am. Chem. Soc. 1985, 107, 256; (b) Cabal, M. P.;
Coleman, R. S.; Danishefsky, S. J. J. Am. Chem. Soc. 1990, 112, 3253.
12. Typical experimental procedure for the syntheses of diacetates of bisphenol (10–
14): To a stirred solution of bisphenol (0.004 mol) in acetic anhydride (10 ml)
In the support of the above proposed mechanism we have also
studied the acetylation of bisphenol 5 in Ac2O with KIO4, CH3-
COONa and CH3COOH (Table 2).
was added sodium metaperiodate (1.28 g, 0.006 mol) in portions over
a
period of 15 min. Stirring was further continued for an appropriate time
period (Table 1) while maintaining the reaction temperature at 75 °C. The
reaction mixture was allowed to cool down to room temperature and then
poured into a saturated solution of sodium bicarbonate (75 ml). The aqueous
layer was then extracted with ethyl acetate (25 ml  3) and organic extracts
were washed with water (20 ml), brine (20 ml) and dried over anhydrous
sodium sulphate. The solvent was removed under reduced pressure to give
the crude product as a dark brown residue, which was chromatographed over
It was found that the use of KIO4 shortens the reaction time as
compared to NaIO4. This may be due to the formation of a conju-
gate base CH3COOK that releases the acetate ion more easily than
CH3COONa. (Table 2) The reaction of 5 in Ac2O with CH3COONa
requires higher temperature and a longer reaction time than with
NaIO4. This indicates the involvement of species 26 in acetylation
during the reaction of bisphenols with NaIO4 or KIO4 in Ac2O. We
have also attempted the acetylation of 5 in Ac2O in the presence
of CH3COOH. The reaction with CH3COOH not only required a high
temperature and longer time but did not reach completion even
under reflux (Table 2).
a
column of silica gel using a mixture of light petroleum/ethyl acetate
furnished white solid as acylated product. (Scheme 2, Table 1) The structures
of the products were confirmed by their analytical and spectral data that are
given below.
4-[1-(4-Acetoxy-3,5-dimethyl-phenyl)-ethyl]-2,6-dimethyl-phenyl ester (10):
mp 112 °C. IR: (KBr): 3049, 1762, 1408, 1253 cmÀ1 1H NMR (400 MHz,
.
CDCl3): d 6.88 (4H, s, aromatic), 3.96 (1H, q, J = 2.6 Hz, CH), 2.31 (6H, s,
OCOCH3), 2.12 (12H, s, 4CH3), 1.54 (3H, d, J = 7.2 Hz, CH3). MS (EI) m/z: Calcd
for C22H26O4 354.18. Found: 354.08 (M+).
This Letter presents the involvement of NaIO4 in the acetylation
of bisphenols and a probable mechanism is also proposed.
4-[1-(4-Acetoxy-3,5-dimethyl-phenyl)-propyl]-2,6-dimethyl-phenyl ester (11):
mp 96 °C. IR: (KBr): 3140, 2985, 1774, 1190 cmÀ1 1H (400 MHz, CDCl3): d
.
6.88 (4H, s, aromatic), 3.50 (1H, t, J = 7.6 Hz, CH), 2.30 (6H, s, OCOCH3), 2.10
(12H, s, 4CH3), 1.97 (2H, m, CH2), 0.82 (3H, t, J = 7.2 Hz, CH3). MS (EI) m/z:
Calcd for C23H26O4 368.47. Found: 368.11 (M+).
Acknowledgments
4-[1-(4-Acetoxy-3,5-dimethyl-phenyl)-butyl]-2,6-dimethyl-phenyl ester (12):
mp 118 °C. IR: (KBr): 3045, 2852, 1762, 1240 cmÀ1 1H NMR (400 MHz,
.
The authors are thankful to Prof. Neelima Kulkarni, Prof. S. R.
Shah and Prof. A. V. Bedekar of the Department of Chemistry, Fac-
ulty of Science, The M. S. University of Baroda for their help in get-
ting the NMR and mass spectral analysis.
CDCl3): d 6.89 (4H, s, aromatic), 3.71 (1H, t, J = 7.8 Hz, CH), 2.29 (6H, s,
OCOCH3), 2.10 (12H, s, 4CH3), 1.92 (2H, m, CH2),1.25 (2H, m, CH2), 0.90 (3H, t,
J = 7.4 Hz, CH3). MS (EI) m/z: Calcd for C24H28O4 382.49. Found: 382.12 (M+).
4-[1-(4-Acetoxy-3,5-dimethyl-phenyl)-1-methyl-ethyl]-2,6-dimethyl-phenyl
ester (13): mp 138 °C. IR: (KBr): 3028, 1764, 1402 cmÀ1 1H NMR (400 MHz,
.
CDCl3): d 6.89 (4H, s, aromatic), 2.31 (6H, s, OCOCH3), 2.09 (12H, s, 4CH3),
1.59 (6H, s, 2CH3). MS (EI) m/z: Calcd for C23H28O4 368.2. Found: 368.10 (M+).
4-[1-(4-Acetoxy-3,5-dimethyl-phenyl)-1-cyclopentyl]-2,6-dimethyl-phenyl ester
References and notes
(14): mp 160 °C. IR: (KBr): 3028, 1764, 1402 cmÀ1 1H NMR (400 MHz,
.
1. (a) Magdziak, D.; Meek, S. J.; Pettus, T. R. R. Chem. Rev. 2004, 104, 1383; (b)
Singh, V. K. Acc. Chem. Res. 1999, 32, 324; (c) Hsu, D. S.; Chou, Y. Y.; Tung, Y. S.;
Liao, C. C. Chem. Eur. J. 2010, 16, 3121; (d) Mcclure, C. K.; Kiessling, A. J.; Link, J.
S. Org. Lett. 2002, 5, 3811.
CDCl3): d 6.49 (4H, s, aromatic), 2.34 (6H, s, OCOCH3), 2.14 (12H, s, 4CH3),
1.84 (4H, m, CH2), 1.61 (4H, m, CH2). MS (EI) m/z: Calcd for C25H30O4 394.5.
Found: 394.21 (M+).