A new method for annulation of the α-pyrone ring

Article abstract of DOI:10.1007/s10593-007-0059-0

New derivatives of coumarin, containing annulated α-pyrone rings, were obtained by reaction of the borate complexes of three isomeric acyl(hydroxy)coumarins with acid anhydrides. It was shown that the borate complex of 3-acetyl-4-hydroxy-2-pyrone also condenses with acetic anhydride to form a derivative containing a new annulated α-pyrone ring.

Full text of DOI:10.1007/s10593-007-0059-0

Chemistry of Heterocyclic Compounds, Vol. 43, No. 4, 2007
A NEW METHOD FOR ANNULATION OF THE α-PYRONE RING
V. F. Traven, I. V. Voevodina, A. V. Manaev, and N. Ya. Podkhalyuzina
New derivatives of coumarin, containing annulated α-pyrone rings, were obtained by reaction of the
borate complexes of three isomeric acyl(hydroxy)coumarins with acid anhydrides. It was shown that the
borate complex of 3-acetyl-4-hydroxy-2-pyrone also condenses with acetic anhydride to form a
derivative containing a new annulated α-pyrone ring.
Keywords: 3-acetyl-4-hydroxy-2-pyrone, acyl(hydroxy)coumarins, borate complexes, α-pyrone ring,
condensation.
Annulation reactions of the pyrone ring are well known both in benzene derivatives and in heterocyclic
compounds–the Kostanecki–Robinson [1, 2], Allan–Robinson [3, 4], and Bargellini [5] reactions. An α-pyrone
but more often a γ-pyrone ring is formed during the reaction, depending on the structure of the reagents and the
conditions. For example, 4-methylcoumarin is mostly formed when o-hydroxyacetophenone is heated with acetic
anhydride in the presence of sodium acetate (the Kostanecki–Robinson reaction), while 2,3-dimethylchromone is
obtained when o-hydroxypropiophenone is heated under the same conditions [1].
Examples of annulation of the pyrone ring in coumarin derivatives are also known [6, 7]. For example,
4-hydroxy-3-propionyl- and 4-hydroxy-3-phenylacetylcoumarins undergo annulation with the formation of new
γ-pyrone rings when heated with acetic anhydride in the presence of sodium acetate. A distinct preference for
annulation of the α-pyrone ring is only observed under the conditions of the Bargellini reaction [5]. When
o-hydroxyacetophenone, o-hydroxybenzophenone, and o-hydroxypropiophenone are heated with acetic
anhydride in the presence of sodium phenylacetate the corresponding coumarins are mostly formed.
While studying the condensation of the borate complexes of acyl(hydroxy)coumarins [8], we established
that their reaction with carboxylic acid anhydrides led to exclusive annulation of the α-pyrone ring.
Me
4
Me
Me
F
F
5
B
3
O
O
B
O
6
5
4
F
3
6
7
R
2
O
B
O
O
O
O
O
7
8
1
F
F
2
O
O
O
Me
3
8
1
F
2
1a,b
1 a R = Me, b R = Et
The borate complexes of 3-hydroxycoumarin (complex 1a), 4-hydroxy-3-propionylcoumarin
(complex 2), and 6-acetyl-7-hydroxy-4-methylcoumarin (complex 3) were condensed with acetic and propionic
anhydrides. Complexes 1-3 were obtained by the reaction of boron trifluoride etherate with the respective
acyl(hydroxy)coumarins in benzene [9].
__________________________________________________________________________________________
D. Mendeleev University of Chemical Technology of Russia, Moscow, 125047; e-mail:
traven@muctr.edu.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 513-517, April,
2007. Original article submitted September 12, 2006.
416
0009-3122/07/4304-0416©2007 Springer Science+Business Media, Inc.

It was found that the action of heat on the complexes 1-3 both with acetic and with propionic anhydride
led to the formation of the respective condensed α-pyrone structures 4-6. This reaction path was confirmed by
the 1H NMR spectra, the mass spectra, and elemental analysis.
O
Me
4
R1
R
5
2
3
6
1
O
3
Me
Me
5
6
10
7
4
R
O
9
8
7
8
4
2
7 O
O
1
O
3
5
10
O
O
8
O
Me
O
1
O
9
O
2
9
10
6
R
4a–d
6a,b
5a,b
4 a R = Me, R1 = H; b R = Et, R1 = H; c R = R1 = Me; d R = Et, R1 = Me.
5, 6 a R = H, b R = Me
The reaction of acyl(hydroxy)coumarins with acid anhydrides most likely takes place according to the
following scheme, shown for the case of the transformation of the complex 1a.
Scheme 1
–
O
R1
O
R1
O
Me
O
O
O
Me
–
[ AcO
O
]
(R1CH2CO)2O
O
O
1a
O
O
7
R1
O
O
OH
∆
4
Me
– H2O
O
Acylation at the hydroxy group probably takes place at the first stage, and the deciding role in such a
reaction path is played by the boron atom coordinated with the oxygen atoms of the acetyl and hydroxyl groups.
The obtained ester 7 is enolized at the ester group. Cyclization of the obtained enolate leads to the coumarin
derivative 4, containing an annulated α-pyrone ring. In the case of enolization of the acetyl group in compound 7
the formation of the γ-pyrone derivatives 8 as final products should be expected, but they were not detected even
in trace quantities (scheme 2).
Scheme 2
O
R1
O
CH2
–
[ AcO
]
–
O
7
R1
O
O
HO
O
R1
O
O
∆
O
O
– H2O
O
O
O
8
417

In order to confirm scheme 1 compound 4a was prepared by an alternative method [6]. The results a
mixed melting test with the sample obtained in this way and compound 4a showed the absence of a melting
point depression. The identity of the two samples was confirmed by spectral data. We also obtained compound
4a in a single stage from 4-hydroxycoumarin, acetic anhydride, and boron trifluoride etherate.
OH
.
Ac2O, BF3 OEt2
4a
O
O
On the other hand, the reaction of 7-hydroxy-4-methylcoumarin with acetic anhydride in the presence of
boron trifluoride etherate stops at the stage of O-acylation with the formation of 7-acetoxy-4-methylcoumarin (9).
The fact that the new α-pyrone ring can be annulated with identical success under our investigated
conditions both on the side of the pyrone ring in the coumarin (compounds 4a-d) and on the side of the benzene
ring (compounds 5a,b and 6a,b) shows that the discussed scheme for annulation of the α-pyrone ring is
universal. This is also demonstrated by the results from study of the reaction of the complex 10 with acetic
anhydride. 4,7-Dimethyl-2H, 5H-dihydropyrano[3,2-c]pyran-2,5-dione (compound 11) was isolated with a yield
of 72% in full agreement with scheme 1.
F
F
O
B
O
O
O
Ac2O
Me
Me
Me
O
O
Me
O
O
10
11
EXPERIMENTAL
1
The H NMR spectra were obtained in CDCl3 on a Bruker WP-200 SY spectrometer (200 MHz) with
TMS as internal standard. The chromatomass spectra were recorded on a PE SCIEX API165 spectrometer
(ELSD UV-254), Synergi 2µ Hydro-RP Mercury column, 20×2.0 mm.
The borate complexes 1a and 2 were obtained as described earlier [9].
Borate Complexes 1b and 3. A solution of (0.1 mol) of acyl(hydroxy)coumarin in the smallest amount
of dry benzene was boiled until the acyl(hydroxy)coumarin had completely dissolved, (15.62 g, 0.11 mol) of
boron trifluoride etherate was added, and the mixture was boiled for 1 h. The precipitate was filtered off, washed
with benzene, and dried in air.
4-Difluoroboryloxy-3-propionyl-coumarin, 3'O→B-Chelate (1b). The yield was 75%; mp 105-107°C
1
(from toluene). H NMR spectrum, δ, ppm (J, Hz): 1.24 (3Н, t, J = 6.5, СН2СН3); 3.02 (2Н, q, J = 6.5,
СН2СН3); 7.33 (2Н, m, Н-7,8), 7.87 (1Н, t, J = 8.3, Н-6); 8.08 (1Н, d, J = 8.3, Н-5). Mass spectrum, m/z
(Irel, %): 266 (45). Found, %: С 54.06; Н 3.44. С12Н9BF2О4. Calculated, %: С 54.14; Н 3.38.
6-Acetyl-7-difluoroboryloxycoumarin, 6'-O→B-chelate (3). The yield was 63%; mp188-190°C (from
toluene). 1H NMR spectrum, δ, ppm (J, Hz): 2.47 (6Н, s, 2СН3); 7.23 (1Н, s, Н-3); 7.71 (1Н, s, Н-5); 8.25 (1Н,
s, Н-8). Mass spectrum, m/z (Irel, %): 266 (55). Found, %: С 54.23; Н 3.29. С12Н9BF2О4. Calculated, %: С 54.14;
Н 3.38.
418

Condensation of Borate Complexes of Acylhydroxycoumarins with Acid Anhydrides. A solution of
1 g of the borate complex 1, 2, or 3 in 7 ml of the anhydride was boiled for 1 h. The precipitate was filtered off
and washed on the filter first with water and then with alcohol. The product was recrystallized from alcohol.
4-Methyl-2H,5H-pyrano[3,2-c]chromene-2,5-dione (4a). The yield was 79%; mp 243-244°C (mp
243°C [6]).
4-Ethyl-2H, 5H-pyrano[3,2-c]chromene-2,5-dione (4b). The yield was 72%; mp 126-128°C. 1H NMR
spectrum, δ, ppm (J, Hz): 1.28 (3Н, t, J = 7.3, CH2CH3); 3.09 (2Н, q, J = 7.3, СН2СН3); 6.25 (1Н, s, H-3); 7.39
(2Н, m, Н-7,8); 8.02 (1Н, t, Н-9); 8.14 (1Н, d, J = 7.9, Н-10). Mass spectrum, m/z (Irel, %): 246 (100). Found,
%: С 69.25; Н 4.07. С14Н10О4. Calculated, %: С 69.42; Н 4.13.
3,4-Dimethyl-2H,5H-pyrano[3,2-c]chromene-2,5-dione (4c). The yield was 71%; mp 222-224°C.
1H NMR spectrum, δ, ppm (J, Hz): 2.10 (3Н, s, 4-СН3), 2.52 (3Н, s, 3-СН3); 7.46 (2Н, m, Н-7,8); 7.82 (1Н, t, J =
7.9, Н-9), 7.96 (1Н, d, J = 7.8, Н-10). Mass spectrum, m/z (Irel, %): 246 (85). Found, %: С 69.27; Н 4.19.
С14Н10О4. Calculated, %: С 69.42; Н 4.13.
4-Ethyl-3-methyl-2H,5H-pyrano[3,2-c]chromene-2,5-dione (4d). The yield was 65%; mp 145-147°C,
1H NMR spectrum, δ, ppm (J, Hz): 1.26 (3Н, t, J = 7.1, 4-СН2СН3); 2.81 (3Н, s, 3-CH3); 3.04 (2Н, q, J = 7.1,
СН2СН3); 7.36-8.11 (4Н, m, Н-7,8,9,10). Mass spectrum, m/z (Irel, %): 260 (95). Found, %: С 70.46; Н 4.57.
С15Н12О4. Found, %: С 70.31; Н 4.69.
4,10-Dimethyl-2H,5H-pyrano[3,2-f]chromene-2,8-dione (5a). The yield was 74%; mp 241-243°C (mp
242°C [10]).
4,9,10-Trimethyl-2H,8H-pyrano[2,3-f]chromene-2,8-dione (5b). The yield was 63%; mp 256-258°C.
1H NMR spectrum, δ, ppm (J, Hz): 2.27 (3Н, s, 10-CH3); 2.48 (3H, s, 4-СН3); 2.83 (3H, s, 9-CH3); 6.27 (1Н, s,
H-3); 7.23 (1Н, d, J = 8.8, Н-5); 7.65 (1H, d, J = 8.8, Н-6). Mass spectrum, m/z (Irel, %): 260 (70). Found, %:
С 70.18; Н 4.53. С15Н12О4. Calculated, %: С 70.31; Н 4.69.
4,6-Dimethyl-2H,8H-pyrano[3,2-g]chromene-2,8-dione (6a). The yield was 75%; mp 318-320°C
(mp 319-320°C [10]).
3,4,6-Trimethyl-2H,8H-pyrano[3,2-g]chromene-2,8-dione (6b). The yield was 67%; mp 289-291°C.
1H NMR spectrum, δ, ppm (J, Hz): 2.25 (3Н, s, 6-СН3); 2.46 (3H, s, 4-CH3); 2.50 (3H, s, 7-CH3); 6.30 (1Н, s,
H-7); 7.26 (1Н, s, Н-5); 7.74 (1H, s, Н-10). Mass spectrum, m/z (Irel, %): 260 (75). Found, %: С 70.42; Н 4.76.
С15Н12О4. Calculated, %: С 70.31; Н 4.69.
Reaction of 3-Acetyl-4-hydroxy- and 8-Acetyl-7-hydroxy-4-Methylcoumarins with Acetic anhydride
in the Presence of BF3·(OEt)2. A solution of (0.01 mol) of hydroxycoumarin in 10 ml of acetic anhydride was
boiled until the hydroxycoumarin had completely dissolved, and (3.12 g, 0.022 mol) of boron trifluoride etherate
was added drop by drop. The reaction mass was boiled for a further 5 h until traces of the hydroxycoumarin and
its borate complex had completely disappeared. The reaction mixture was cooled, and the crystals that separated
were filtered of and washed on the filter with water and alcohol. The product was recrystallized from ethanol.
7-Acetoxy-4-methylcoumarin (9). The yield was 78%; mp 150-152°C (mp 150-151°C [11]).
3-Acetyl-4-difluoroboryloxy-6-methylpyran-3-one, 3'-O→B-Chelate (10). This compound was
obtained as described earlier [12].
Reaction of the Borate Complex of 3-Acetyl-4-hydroxy-7-methyl-2-pyrone (10) with Acetic
Anhydride. A solution of (1 g) of the borate complex 10 in 6 ml of the anhydride was boiled for 1 h. The
precipitate was filtered off, washed on the filter with water and then with alcohol, and recrystallized from alcohol.
4,7-Dimethyl-2H, 5H-dihydropyrano[3,2-c]pyran-2,5-dione (11). The yield was 72%; mp 211-213°C
(mp 212-213°C [13]).
419

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