Reactions of 4-Oxo-4H-1-benzopyran-3-carboxaldehydes with Pentane-2,4-dione in Acidic Medium - A New Route to Dihydroxybenzophenone Derivatives

Article abstract of DOI:10.1039/a804173c

Reaction of the title aldehyde 1 with acetylacetone 2 gives benzophenone 8 along with the Knoevenagel-type product 5 under acidic conditions.

Full text of DOI:10.1039/a804173c

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802 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 802±803$
Reactions of 4-Oxo-4H-1-benzopyran-3-
carboxaldehydes with Pentane-2,4-dione in Acidic
MediumÐa New Route to Dihydroxybenzophenone
Derivatives$
Chandrakanta Bandyopadhyay,* Kumar Ranabir Sur and
Ranjan Patra
Department of Chemistry, R. K Mission Vivekananda Centenary College, Rahara,
North 24 Parganas, West Bengal, 743186 India
Reaction of the title aldehyde 1 with acetylacetone 2 gives benzophenone 8 along with the Knoevenagel-type product 5
under acidic conditions.
Aldehyde
1
reacts with various active methylene
Another interesting observation is in the mode of
addition of reagents. The ®rst mode, which is described in
the Experimental section produced compounds 5 and 8. But
in the second mode, when an equimolar amount of 1a or
1b, 2 and a catalytic amount of HCl are taken together in
acetic acid at room temperature and then heated for 2 h at
70±80 8C, only 5 (40±45%) was obtained along with some
unreacted aldehyde (010%). No trace of 8 was observed
even by TLC. This observation may be rationalised by
considering the more ready protonation of the aldehydic
oxygen of the more basic 3-formylchromone 1 than that of
acetylacetone which then undergoes 1,2-addition and ®nally
gives 5 (Scheme 2).
compounds1 in basic media to produce mainly
Knoevenagel-type condensation products. With 1, malon-
amide or cyanoacetamide produces pyridone derivatives2
which are assumed to form via the Knoevenagel-type
condensation product. Similarly, compound 5 or 9 or a
mixture of 1 and 2 or 1 and ethyl acetoacetate produces
pyridine derivatives3 when treated with ammonium acetate
in ethanol. A benzophenone derivative is produced when 9a
is treated with ethyl acetoacetate in piperidine±ethanol or
from 1a in one-pot using the same reaction conditions but
with excess ethyl acetoacetate.4
Recapitulating the mechanism of the base catalysed
condensation of 1 and 2Ðattack of the nucleophile at the
2-position of pyran ring, followed by ring opening and
recyclisation to 4 and subsequent elimination of water to 5
(Scheme 1, path a),1 the ring opened intermediate phenoxide
of 3 may follow an alternative route (Scheme 1, path b)
where the enolate of 6 can cyclise and could ultimately form
8. But no 8 was obtained under basic conditions. The
phenoxide ion is probably nucleophilic enough to favour
path a. The reaction sequence may follow path b at least to
some extent if the nucleophilic character of the phenoxide
ion is decreased somehow. This is indeed achieved by carry-
ing out the reaction in an acidic medium. In fact, 8 was
obtained in low to moderate (15±30%) yield along with 5
(30±40%) when a solution of 1 in acetic acid is added to a
preheated (70±80 8C) mixture of 2 in acetic acid containing
a catalytic amount of HCl. Compound 54 fails to give 8
when heated in HCl±AcOH at 70±80 8C, which rules out the
possibility of formation of 8 via 5. Various other attempts,
e.g. stirring 5 at room temperature with Al2O3±DMF,
AlCl3±CS2, H2SO4 or PPA (DMF ˆ dimethylformamide;
PPA ˆ polyphosphoric acid) heating with AlCl3 in the solid
phase at 120 8C or re¯uxing with K-10 montmorillonite
in benzene or toluene, were made to form 8, but all
failed. Hence, formation of 8 is rationalised as followsÐ
1,4-addition of the enol form of 2 to 1 followed by ring
opening generates 3 which then enolises to 6. Compound 8
is obtained from 6 by cyclisation ( 47) and subsequent
dehydration and tautomerisation (Scheme 1, path b). A rela-
tively high yield of 8d also supports the proposed mechan-
ism. The presence of a nitro group at the para position
of the hydroxy group in 3 decreases the nucleophilicity of
the hydroxy group and path b becomes the preferred one.
5d could not be isolated from the reaction mixture of 1d
and 2. So it is obvious that path a is less favourable here.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
Scheme 1 a, R ˆ H; b, R ˆ Me; c, R ˆ Cl; d, R ˆ NO2

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J. CHEM. RESEARCH (S), 1998 803
8b: yield 15%; mp 141 8C; dH 2.24 (CH3, s), 2.64 (COCH3, s),
7.00 (H-3', d, J 9), 7.12 (H-5, d, J 9), 7.32±7.44 (H-4', H-6', m), 7.88
(H-6, dd, J 9 and 1.8), 8.20 (H-2, d, J 1.8), 11.60 (OHb, exchange-
1
able, s) and 12.66 (OHa, exchangeable, s); ꢀmax/cm 3200±2750,
1650, 1640, 1600 (Found: C, 71.09; H, 5.24. C16H14O4 requires
C, 71.10; H, 5.22%).
Scheme 2
8c: yield 20%; mp 144 8C; dH 2.71 (COCH3, s), 7.07 (H-3', d, J
9), 7.12 (H-5, d, J 9), 7.48 (H-4', dd, J 9 and 1.8), 7.55 (H-6', d,
J 1.8), 7.86 (H-6, dd, J 9 and 1.8), 8.20 (H-2, d, J 1.8), 11.65
Experimental
1
(OHb, exchangeable, s) and 12.72 (OHa, exchangeable, s); ꢀmax/cm
All mp values are uncorrected. IR spectra were recorded on
a Perkin Elmer 782 spectrometer as KBr discs. 1H NMR spectra
were recorded in CDCl3 on a Bruker AM 300L spectrometer using
Me4Si as internal standard and the coupling constants are expressed
in Hz.
3300±2750, 1660, 1640, 1600 (Found: C, 62.60; H, 3.87. C15H11ClO4
requires C, 62.40; H, 3.84%).
8d: yield 30%; mp 174 8C; dH 2.71 (COCH3, s), 7.18 (H-5, d, J 9),
7.21 (H-3', d, J 9), 7.92 (H-6, dd, J 9 and 1.8), 8.25 (H-2, d,
J 1.8), 8.42 (H-4', dd, J 9 and 1.8), 8.62 (H-6', d, J 1.8), 12.49
General Procedure5 for the Formation of 3-Acetyl-2',4-dihydroxy-
5'-substituted Benzophenone 8.ÐConcentrated HCl (2±3 drops) was
added to acetylacetone (500 mg, 5 mmol) in acetic acid (5 ml) at
70±80 8C. The reagent mixture was stirred at that temperature
for 15 min. A solution of 1 (5 mmol) in acetic acid (15 ml) was
added dropwise. The resultant solution was stirred for 2 h at that
temperature. The dark-red reaction mixture was cooled and poured
on to crushed ice (100 g). The solid deposit was ®ltered, washed
with water and dried. The crude mixture was chromatographed
over silica gel (100±200 mesh) using 5% ethyl acetate in light
petroleum as eluent to give 8 from the ®rst few fractions and
then 53,4 (30±40%) from the later fractions of the same eluent.
Compound 5d could not be isolated from the reaction mixture of
1d and 2. Characterisation data of 8 are as follows:
1
(OHa, exchangeable, s) and 12.81 (OHb, exchangeable, s); ꢀmax/cm
3200±2800, 1660, 1640, 1600 (Found: C, 59.81; H, 3.66; N, 4.67.
C
15H11NO6 requires C, 59.80; H, 3.68; N, 4.65%).
Received, 3rd June 1998; Accepted, 1st September 1998
Paper E/8/04173C
References
1 Reviews: G. P. Ellis, Heterocyclic Compounds, ed. A. Weisberger,
Interscience, New York, 1977, vol. 35, p. 921; C. K. Ghosh,
J. Heterocycl. Chem., 1983, 20, 1437; G. Sabitha, Aldrichim. Acta,
1996, 29, 15.
8a: yield 17%; mp 128 8C; dH 2.66 (COCH3, s), 6.88±6.96 (H-3',
H-5', m), 7.12 (H-5, d, J 9), 7.44±7.66 (H-4', H-6', m), 7.92 (H-6,
dd, J 9 and 1.8), 8.28 (H-2, d, J 1.8), 11.84 (OHb, exchangeable, s)
2 A. Nohara, T. Ishigura and Y. Sanno, Tetrahedron Lett., 1974,
1183.
3 C. K. Ghosh and S. Khan, Synthesis, 1981, 903.
4 W. D. Jones and W. L. Albrecht, J. Org. Chem., 1976, 41, 706.
5 O. Sirkecioglue, N. Talini and A. Akar, J. Chem. Res. (S), 1995,
502.
1
and 12.72 (OHa, exchangeable, s);
ꢀ
max/cm
3120±2750, 1650,
1630, 1600 (Found: C, 70.42, H, 4.75. C15H12O4 requires C, 70.30;
H, 4.72%).