4,4′-spirodichroman-2-ones as unexpected products from the condensation of resorcinols and dimethyl acetonedicarboxylate

Article abstract of DOI:10.1007/s10593-007-0041-x

As a result of the reaction of resorcinols with dimethyl acetonedicarboxylate under the conditions of the Pechmann reaction derivatives of 4,4′-spirodichroman-2-one were isolated as anomalous condensation products. Their structure was demonstrated by spectral methods. A mechanism was proposed for the formation of the spirodilactone system.

Full text of DOI:10.1007/s10593-007-0041-x

Chemistry of Heterocyclic Compounds, Vol. 43, No. 3, 2007
4,4'-SPIRODICHROMAN-2-ONES AS UNEXPECTED PRODUCTS
FROM THE CONDENSATION OF RESORCINOLS AND DIMETHYL
ACETONEDICARBOXYLATE
I. P. Dubovik1, M. M. Garazd1, and V. P. Khilya2
As a result of the reaction of resorcinols with dimethyl acetonedicarboxylate under the conditions of the
Pechmann reaction derivatives of 4,4'-spirodichroman-2-one were isolated as anomalous condensation
products. Their structure was demonstrated by spectral methods. A mechanism was proposed for the
formation of the spirodilactone system.
Keywords: coumarins, coumarin-4-acetic acids, spirodilactones, 4,4'-spirodichroman-2-one, Pechmann
reaction.
The reaction of phenols and the esters of β-keto acids in the presence of dehydrating agents such as
concentrated sulfuric acid is known as the Pechmann reaction [1]. This condensation has found widespread use
in the synthesis of compounds based on the benzopyran-2-one system [2, 3]. The course of the reaction and the
structure of the products depend on the nature of the phenols and the β-keto esters and also on the nature of the
condensing agent. The Pechmann reaction can also give other products and, in particular, chromones,
diarylglutamic acids and their anhydrides, dilactones, etc. [1, 4].
In the reaction of resorcinol and dimethyl acetonedicarboxylate in methanol in the presence of
concentrated sulfuric acid as condensing agent, in addition to the expected product of the Pechmann reaction
[methyl 7-hydroxycoumarin-4-acetate (1)] we also obtained a 16% yield of the product 2, which differed from
the benzopyran-2-one derivatives in its spectral characteristics. In the UV spectrum of compound 2 there is one
strong absorption maximum at 204 nm, whereas the derivatives of the 7-hydroxycoumarins have two strong
maxima at 210-225 and 310-325 nm [5]. In the IR spectrum of compound 2 there are strong bands at 1745
(characteristic of the saturated lactone) and 3435 cm−1 (due to the stretching vibrations of the phenol group). The
1H NMR spectrum of the product 2 in the region of the aromatic protons contains a system of ABX protons, a
broad one-proton singlet for the hydroxy group at 9.81 ppm, and two one-proton doublets with J = 15.0 Hz at
2.97 and 3.16 ppm. The 13C NMR spectrum contains a signal at 38.20 ppm for the quaternary carbon atom. A
molcular-ion peak of high intensity with m/z 312 [M]+ (96%) is observed in the mass spectrum of compound 2.
Compound 2 is consequently 4,4'-spirodi[7-hydroxychroman-2-one].
During the condensation of 2-methylresorcinol and dimethyl acetonedicarboxylate under analogous
conditions methyl 7-hydroxy-8-methylcoumarin-4-acetate (3) and 4,4'-spirodi[7-hydroxy-8-methylchroman-
2-one] (4) were isolated with yields of 64 and 11% respectively.
__________________________________________________________________________________________
1Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine,
2
Kiev 02094, Ukraine; e-mail: gmm@i.com.ua. Taras Shevchenko Kiev National University, Kiev 02033,
Ukraine; e-mail: vkhilya@mail.univ.kiev.ua.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3,
pp. 352-356, March, 2007. Original article submitted April 18, 2005. Revision submitted September 24, 2006.
0009-3122/07/4303-0277©2007 Springer Science+Business Media, Inc.
277

It can be supposed that the reaction of resorcinols and dimethyl acetonedicarboxylate takes place through
electrophilic alkylation and lactonization with the formation of a derivative of 4,7-dihydroxychroman-2-one as
intermediate compound. Dehydration of the latter with concentrated sulfuric acid leads to the formation of
coumarin-4-acetate esters 1 and 3. Condensation of the intermediate with another molecule of resorcinol leads to
the formation of the 4,4'-spirodichroman-2-one system. It should be noted that the use of two mols of the
resorcinol to one mol of the dimethyl acetonedicarboxylate in the condensation leads to an insignificant increase
in the yield of the respective 4,4'-spirodichroman-2-one 2, and the main product of the Pechmann reaction is the
coumarin-4-acetate ester 1.
Alkylation of the phenolic hydroxyls of compounds 2 and 4 under the conditions of the Williamson
reaction by the action of dimethyl sulfate in acetone leads to the formation of the corresponding methyl ethers 5
and 6.
O
O
O
R
HO
OH
MeO
OMe
MeOH, H2SO4
R
R
O
HO
O
O
O
HO
_
H2O
OH
OMe
O
O
R
OMe
1, 3
R
HO
OH
R
O
O
R
MeO
O
O
O
R
HO
(MeO)2SO2
K2CO3
O
O
OMe
O
OH
5, 6
2, 4
1, 2, 5 R = H, 3, 4, 6 R = Me
The structure of the isolated side products from the Pechmann condensation and their methyl ethers was
confirmed by the data from mass spectrometry. The mass spectra of compounds 2 and 4-6 contain strong
molcular-ion peaks corresponding to their empirical formulas. The fragmentation of the compounds under
electron impact is fairly general in nature. The presence of the [M−28], [M+−42], and [M+−70] peaks in the mass
spectra of compounds 2 and 4-6 makes it possible to suggest the main paths for the fragmentation of the
molcules under electron impact.
It should also be noted that the formation of 4,4'-spirodichroman-2-ones is not observed during the
condensation of phloroglucinol, pyrogallol, and orcinol with dimethyl acetonedicarboxylate, and the reaction
takes place with the exclusive formation of the corresponding methyl coumarin-4-acetates.
278

.
.
+
+
R
R
O
R1O
O
R
O
R1O
O
R
O
O
O
OR1
OR1
2 m/z 312 (96%)
4 m/z 340 (100%)
5 m/z 340 (100%)
6 m/z 368 (100%)
2 m/z 284 (10%)
4 m/z 312 (4%)
5 m/z 312 (8%)
6 m/z 340 (15%)
.
.
+
+
R
R
R1O
R1O
O
O
O
HO
R
HO
R
OR1
OR1
2 m/z 270 (59%)
4 m/z 298 (71%)
5 m/z 298 (72%)
6 m/z 326 (83%)
2 m/z 242 (100%)
4 m/z 270 (83%)
5 m/z 270 (63%)
6 m/z 298 (36%)
EXPERIMENTAL
The reactions and the individuality of the compounds were monitored by TLC on Merck 60 F254 plates
with 9:1 and 95:5 chloroform–methanol solvent systems as eluants. The melting points were determined on a
Kofler hot bench. The IR spectra were measured on a Nicolet FTIR Nexus 475 spectrometer, and the UV spectra
1
were obtained on a Specord M-40 spectrometer. The H and 13C NMR spectra were recorded on Varian VXR-
300 (300 and 75 MHz respectively) and Varian Mercury-400 (400 and 100 MHz respectively) in DMSO-d6 with
TMS as internal standard. The mass spectra were recorded on a Varian MAT-311A instrument with ionization
energy 70 eV.
Pechmann Condensation (General Procedure). To a cooled solution (0°C) of 200 ml of the respective
polyphenol and dimethyl acetonedicarboxylate (20 mmol, 29.5 ml) in 30 ml of absolute methanol with vigorous
stirring and cooling we added dropwise 20 ml of concentrated sulfuric acid. The reaction mixture was stirred
until completely solid and left at room temperature overnight. The mixture was transferred to 500 ml of iced
water, the precipitate was filtered off and crystallized from methanol, and compound 1 or 3 was obtained. The
methanol mother solution was evaporated under the vacuum of a rotary evaporator, the oily residue was
crystallized from acetonitrile, and compound 2 or 4 was isolated.
279

Methyl 2-(7-Hydroxy-2- oxochromen-4-yl) acetate (1). The yield was 60%; mp 215-217 ºС (mp 220 ºС
[6, 7], 221-223 ºС [8]). IR spectrum, ν, cm-1: 3360 (OH), 1726 (C=O), 1690 (C=O), 1680, 1604 (C=C), 1400, 1342,
1
1204, 1140. UV spectrum (MeCN), λmax (log ε): 202 (4.78), 218 (4.34), 322 (4.25). H NMR spectrum, δ, ppm
(J, Hz): 3.66 (3H, s, COOCH3), 3.95 (2Н, s, СН2-4), 6.24 (1Н, s, Н-3), 6.74 (1Н, d, J = 2.1, Н-8), 6.81 (1Н, dd,
J = 2.1, J = 8.7, Н-6), 7.52 (1Н, d, J = 8.7, Н-5), 10.56 (1Н, br. s, ОН-7).
Methyl 2-(7-Hydroxy-8-methyl-2-oxochromen-4-yl)acetate (3). The yield was 64%; mp 190-193 ºС.
IR spectrum, ν, cm−1: 3228 (OH), 2956, 1724 (C=O), 1692 (C=O), 1602 (C=C), 1576, 1320, 1258, 1090, 874,
1
850, 726. UV spectrum (MeCN), λmax (log ε): 203 (4.67), 220 (4.21), 322 (4.14). H NMR spectrum, δ, ppm (J,
Hz): 2.18 (3Н, s, 8-СН3), 3.65 (3Н, s, СООСН3), 3.86 (2Н, s, СН2-4), 6.16 (1Н, s, Н-3), 6.82 (1Н, d, J = 8.7, Н-
6), 7.27 (1Н, d, J = 8.7, Н-5), 10.33 (1Н, br. s, ОН-7). The ester (3) was then used without further purification.
4,4'-Spirodi[7-hydroxychroman-2-one (2). The yield was 16%, mp. 308.5-309.5 ºС. IR spectrum,
ν, cm-1: 3435 (OH), 1745 (C=O), 1620 (C=C), 1441, 1330, 1285, 1256, 1190, 1075. UV spectrum (EtOH),
1
λ
max (log ε): 204 (4.90). H NMR spectrum, δ, ppm (J, Hz): 2.97 (1Н, d, J = 5.0, Н-3a), 3.16 (1Н, d, J = 15.0,
Н-3b), 6.51 (1Н, dd, J = 2.1, J = 8.7, Н-6), 6.55 (1Н, d, J = 2.1, Н-8), 6.74 (1Н, d, J = 8.7, Н-5), 9.81 (1Н, br. s,
ОН-7). 13C NMR spectrum, δ, ppm: 38.20 (C-4), 40.19 (C-3), 105.56 (C-8), 112.69 (C-6), 118.42 (C-5a), 126.84
(C-5), 152.03 (C-8a), 158.66 (C-7), 167.11 (C-2). Mass spectrum (EI), m/z (Irel, %): 312 [М]+ (96), 284 (10), 270
(59), 253 (14), 242 (100), 225 (13), 213 (15), 197 (7), 185 (5), 157 (3). Found, %: С 65.12; Н 3.61. С17Н12О6.
Calculated, %: С 65.39; Н 3.87.
4,4'-Spirodi[7-hydroxy-8-methylchroman-2-one] (4). The yield was 11%, mp 320-321 ºС. IR
spectrum, ν, cm-1: 3444 (OH), 1748 (C=O), 1620 (C=C), 1432, 1332, 1290, 1270, 1256, 1198, 1076. UV
1
spectrum (EtOH), λmax (log ε): 207 (4.75). H NMR spectrum, δ, ppm (J, Hz): 2.09 (3H, s, 8-CH3), 2.99 (1Н, d,
J = 15.2, Н-3a), 3.19 (1Н, d, J = 15.2, Н-3b), 6.59 (1Н, d, J = 9.2, Н-6), 6.62 (1Н, d, J = 9.2, Н-5), 9.84 (1Н,
br. s, ОН-7). 13C NMR spectrum, δ, ppm: 9.16 (CH3-8), 38.42 (C-4), 40.01 (C-3), 111.44 (C-8), 112.81 (C-6),
116.84 (C-5a), 123.32 (C-5), 150.16 (C-7), 156.76 (C-8a), 167.27 (C-2). Mass spectrum (EI), m/z (Irel, %): 340
[М]+ (100), 312 (4), 298 (71), 297 (71), 281 (14), 270 (83), 253 (22), 241 (9), 227 (6), 198 (5). Found, %: С
66.92; Н 4.53. С19Н16О6. Calculated, %: С 67.05; Н 4.74.
4,4'-Spirodi[7-methoxychroman-2-ones] 5 and 6. To a solution of 5 mmol of the hydroxy derivative 3
or 4 in 20 ml of absolute acetone, containing 2.76 g (20 mmol) of freshly calcined potassium carbonate, while
stirring and heating we added 0.95 ml (10 mmol) of dimethyl sulfate. The reaction mixture was kept at 50-60°C
for 1-2 h. (The end of the reaction was determined by TLC.) After cooling to room temperature the mixture was
transferred to 200 ml of a 1 N solution of sulfuric acid, and the precipitated product was filtered off and
crystallized from aqueous methanol.
4,4'-Spirodi[7-methoxychroman-2-one] (5). The yield was 94%; mp 194-195.5 °С. IR spectrum,
ν, cm-1: 1776 (С=0), 1620 (С=С), 1584 (С=С), 1512, 1504, 1440, 1264, 1162, 1120, 978. UV spectrum (EtOH),
1
λmax (log ε): UV spectrum (MeCN), λmax (log ε): 205 (4.85). H NMR spectrum, δ, ppm (J, Hz): 3.10 (Н, d,
J = 14.8, Н-3а), 3.32 (Н, d, J = 14.8, Н-3b), 3.77 (3Н, s, 7-СН30), 6.78 (Н, dd, J = 2.4, J = 8.8, Н-6), 6.87 (Н, d,
J = 2.4, Н-8), 6.89 ( Н , d, J = 8.8, Н-5). 13C NMR spectrum, δ, м. д.: 38.17 (С-4), 40.24 (С-3), 56.20 (7-СН30),
103.36 (С-8), 111.66 (С-6), 118.10 (С-5а), 127.04 (С-5), 152.16 (С-8а), 160.76 (С-7), 166.88 (С-2). Mass
spectrum (EI), m/z (Irel, %): 340 [М]+ (100), 312 (8), 298 (72), 281 (13), 270 (63), 255 (45), 239 (35), 227 (5), 211
(5), 199 (4). Found, %: С 69.79; Н 4.66. С19Н16О6. Calculated, %: С 67.05; Н 4.74.
4,4'-Spirodi[7-methoxy-8-methylchroman-2-one] (6). The yield was 95%; mp 259-260.5 °С. IR
spectrum, ν, cm-1: 1784 (С=0), 1618 (С=С), 1592 (С=С), 1496, 1430, 1304, 1252, 1180, 1116, 1076. UV
1
spectrum (EtOH), λmax (log ε): 208 (4.88). H NMR spectrum, δ, ppm (J, Hz): 2.13 (3Н, s, 8-СН3), 3.05 (Н, d,
J = 15.2, Н-3а), 3.27 (Н, d, J = 15.2, Н-3b), 3.80 (3Н, s, 7-ОСН3), 6.76 (Н, d, J = 8.8, Н-6), 6.81 (Н, d, J = 8.8,
Н-5). 13С NMR spectrum, δ, ppm: 9.16 (8-СН3), 38.55 (С-4), 40.24 (С-3), 56.41 (7-СН30), 107.39 (С-8), 114.38
280

(С-6), 118.54 (С-5а), 123.72 (С-5), 149.76 (С-7), 158.36 (С-8а), 166.99 (С-2). Mass spectrum (EI), m/z (Irel, %):
368 [М]+ (100), 340 (15), 326 (83), 325 (84), 309 (13), 298 (36), 283 (31), 267 (55), 255 (6), 184 (9), 165 (22),
149 (20). Found, %: С 68.21; Н 5.21. С21Н20О6. Calculated, %: С 68.47; Н 5.47.
REFERENCES
1.
2.
Organic Reactions [Russian translation], Izd. Inostr. Lit., Moscow (1956), Vol. 7, p. 7.
R. Elderfield (editor), Heterocyclic Compounds [Russian translation], Izd. Inostr. Lit., (1954), Vol. 2,
p. 134.
3.
D. Barton and W. D. Ollis (editors), Comprehensive Organic Chemistry [Russian translation], Khimiya,
Moscow (1985), Vol. 9, p. 67.
4.
5.
J. L. Belletire, K. Donahue, and M. Kellogg, J. Heterocycl. Chem., 16, 803 (1979).
M. E. Perel’son, Yu. N. Sheinker, and A. A. Savina, Spectra and Structure of Coumarins, Chromones,
and Xanthones [in Russian], Meditsina, Moscow (1975).
6.
7.
8.
W. Baker, C. N. Haksar, and J. F. W. McOmie, J. Chem. Soc., 170 (1950).
J. Krejcoves, J. Drobnik, J. Jokl, and J. Kalal, Collect. Czech. Chem. Commun., 2211 (1979).
R. C. Elderfield and A. C. Mehta, J. Med. Chem., 921 (1967).
281