Chromone studies. Part 13.1 Synthesis and electron-impact mass spectrometric studies of 5-hydroxy-2-isopropyl-7-methoxychromone, a constituent of the medicinal plant Baeckea frutescens, and side-chain analogues

Article abstract of DOI:10.1021/np030097d

5-Hydroxy-2-isopropyl-7-methoxychromone (1d), a chromone constituent isolated from the aerial parts of Baeckea frutescens, and four analogues (1a-c and 1e), all of which exhibit toxicity to the brine shrimp Artemia salina, have been prepared from 2′,4′,6′-trihydroxyacetophenone. High-resolution mass spectrometric analysis has permitted elucidation of the fragmentation patterns exhibited by these systems following electron-impact ionization.

Full text of DOI:10.1021/np030097d

1144
J . Nat. Prod. 2003, 66, 1144-1146
Ch r om on e Stu d ies. P a r t 13.1 Syn th esis a n d Electr on -Im p a ct Ma ss Sp ectr om etr ic
Stu d ies of 5-Hyd r oxy-2-isop r op yl-7-m eth oxych r om on e, a Con stitu en t of th e
Med icin a l P la n t Ba eckea fr u tescen s, a n d Sid e-Ch a in An a logu es
Christopher A. Gray, Perry T. Kaye,* and Aloysius T. Nchinda
Department of Chemistry, Rhodes University, Grahamstown, 6140, South Africa
Received March 7, 2003
5-Hydroxy-2-isopropyl-7-methoxychromone (1d ), a chromone constituent isolated from the aerial parts
of Baeckea frutescens, and four analogues (1a -c and 1e), all of which exhibit toxicity to the brine shrimp
Artemia salina, have been prepared from 2′,4′,6′-trihydroxyacetophenone. High-resolution mass spectro-
metric analysis has permitted elucidation of the fragmentation patterns exhibited by these systems
following electron-impact ionization.
Sch em e 1
Chromones are widely distributed in nature, and many
are known to possess useful medicinal properties.2 Among
these are the chromone derivatives, granulosin [7,8-(me-
thylenedioxy)-2-propylchromone], isolated by Schiff and co-
workers3 from the bark of Galipea granulosa, and 5-hydroxy-
2-isopropyl-7-methoxychromone 1d , recently isolated by
Tsui and Brown4 from the aerial parts of Baeckea frutescens
L., a plant used in traditional Chinese medicine for treating
rheumatism and snake-bite. As part of an ongoing study
of chromone systems, we previously described an efficient
synthesis of granulosin and structural analogues5 and now
report the preparation of 5-hydroxy-2-isopropyl-7-meth-
oxychromone (1d ) and several analogues (1a -c and 1e),
their toxicity to the brine shrimp Artemia salina, and an
investigation of their EIMS fragmentation patterns.
Retrosynthetic analysis suggested that synthesis of 1d
could be achieved via the condensation of ethyl 2-methyl-
propanoate (3) with 2′,6′-dihydroxy-4′-methoxyacetophe-
none (2), obtainable, in turn, from 2′,4′,6′-trihydroxyace-
tophenone (4) (Scheme 1). However, attempted methylation
of the commercially available 4, using 1 equiv of dimethyl
sulfate and 1 equiv of K2CO3, as described by Huang et
al.,6 gave a mixture, shown by 1H NMR analysis to
comprise the desired 2′,6′-dihydroxy-4′-methoxyacetophe-
none (2; <40%), the dimethylated analogue (5), and start-
ing material. Consequently, it was decided to exploit the
facile dimethylation and attempt selective demethylation
of the 6′-methoxy group later in the synthetic sequence.
The resistance of the 2′-hydroxy group to methylation
under these conditions is attributed to hydrogen-bonded
chelation with the acetyl carbonyl oxygen. The existence
of such hydrogen bonding is clearly evident in the signifi-
cant deshielding of the 2-hydroxyl proton (δΗ ca. 13.9) in
the 1H NMR spectrum of 2′-hydroxy-4′,6′-dimethoxy-
acetophenone (5). Following this strategy (Scheme 2),
reaction of 4 with 2 equiv of dimethyl sulfate and 2 equiv
of anhydrous K2CO3 in acetone under reflux for 5 h gave
57 in 90% yield. The 13C NMR spectrum of 5 revealed nine
distinct carbon signals, instead of the expected 10, the
intense signal at δC 55.4 reflecting coincidence of the two
methoxy carbon signals, a conclusion supported by COSY,
HMQC, and HMBC data.
Sch em e 2a
a
Reagents: (i) Me2SO4 (1 equiv), K2CO3 (1 equiv), acetone; (ii) Me2SO4
(2 equiv), K2CO3 (2 equiv), acetone; (iii) NaOEt, EtOH; (iv) RCO2Et; (v)
AcOH, H2SO4; (vi) Ac2O, HI, 115 °C, 30 min.
reaction with the series of ethyl carboxylate esters [RCO2-
Et; R ) CH3, CH3CH2, CH3CH2CH2, (CH3)2CH, PhCH2],
gave mixtures, indicated by 1H NMR spectroscopy, to
contain the corresponding C-acylated products (existing as
the respective enol tautomers, formulated as structures
6a -e) and their cyclized derivatives 7a -e. Treatment of
these mixtures with HOAc and H2SO4 afforded the 5,7-
dimethoxychromone derivatives 8a -e. Selective demethy-
lation at the C-5 position was achieved in yields ranging
from 55 to 80%, using a mixture of boiling Ac2O and
hydriodic acid,8 and the structures of the resulting 5-hy-
The dimethylated intermediate (5) was then treated with
2 equiv of NaOEt in EtOH to afford an enolate which, on
* To whom correspondence should be addressed. Tel: +27 46 603 8254.
Fax: +27 46 622 5109. E-mail: P.Kaye@ru.ac.za.
10.1021/np030097d CCC: $25.00
© 2003 American Chemical Society and American Society of Pharmacognosy
Published on Web 08/02/2003

Notes
J ournal of Natural Products, 2003, Vol. 66, No. 8 1145
Ta ble 1. Summary of Artemia salina Biological Assay Data for
Compounds 1a -ea
bonylation to give the analogous, ring-contracted fragment
VId (m/z 191). In path C, elimination of HCHO, charac-
teristic of aromatic methyl ethers,13 affords the radical-
cation Vd (m/z 204), subsequent decarbonylation of which
leads to yet another ring-contracted fragment, VIId (m/z
176). In path D, the molecular ion Id undergoes the
expected retro-Diels-Alder reaction (RDA), characteristic
of the chromone nucleus,12 and elimination 2-methyl-1-
butyne, affording the ketene IXd (m/z 166); successive
decarbonylation then gives the cyclopentadienyl fragments
Xd (m/z 138) and XId (m/z 110). The formation of fragment
VIIId (m/z 167) (path E) from the molecular ion is at-
tributed to the [RDA+H]+ process, which is also common
in chromone derivatives;12 subsequent deprotonation pro-
vides an alternative route to fragment IXd .
95% confidence interval
(µg.mL-1
)
compd
LC50 (µg mL-1
)
upper limit
lower limit
1a
1b
1c
1d
1e
112.2
39.0
31.5
23.8
516.6
94.8
35.7
27.4
21.2
445.4
132.9
42.6
36.4
26.8
599.2
a
Estimates of median lethal concentrations obtained using the
trimmed Spearman-Karber method.9
Ta ble 2. Summary of Artemia salina Biological Assay Data for
Compounds 8a -ea
95% confidence interval
While most of the fragments of types I-XI were observed
in the mass spectra of the analogues 1a -c,e, additional
fragments, which are supported by the linked-scan data
and which arise from the presence of the phenyl group,
were observed for the 2-benzyl derivative 1e (Scheme 4,
Supporting Information). Thus, formation of fragment XIIe
(m/z 115) is attributed to heterolytic fission of the molecular
ion via an RDA-type process; in this case, however, effective
stabilization presumably accounts for the formation of the
benzylic-propargylic carbocation. The tropylium cation
XIIIe (m/z 91) and the phenyl cation XIVe (m/z 77) are
typical of alkyl benzenes. Not surprisingly, the fragmenta-
tions exhibited by 2-isopropyl-5,7-dimethoxychromone (8d )
and its side-chain analogues (8a -c and 8e) correlate closely
with those of the monomethoxy compounds 1a -e.14
(µg.mL-1
)
compd
LC50 (µg mL-1
)
upper limit
lower limit
8a
8b
8c
8d
8e
315.1
200.1
106.0
94.2
223.9
182.3
95.0
82.5
217.1
443.3
219.7
118.3
107.5
281.8
247.3
a
Estimates of median lethal concentrations obtained using the
trimmed Spearman-Karber method.9
droxy-7-methoxychromone derivatives (1a -e) were con-
firmed by HREIMS and spectroscopic (IR, 1H and 13C NMR)
analysis. The spectroscopic data obtained for 5-hydroxy-
2-isopropyl-7-methoxychromone (1d ) corresponded to those
reported for the natural product.4
Exp er im en ta l Section
To evaluate the biological activity of the 2-alkyl-5-
hydroxy-7-methoxychromones (1a -e) and their 5,7-di-
methoxy precursors (8a -e), Artemia salina larvicidal bio-
assays were performed using the method reported by Solis
et al.9 The trimmed Spearman-Karber method10 was used
to obtain estimates of median lethal concentrations of the
A. salina mortality data for compounds 1a -e and 8a -e.
The LC50 values obtained for the monomethoxy analogues
1a -e (Table 1) indicate that they are, in general, consider-
ably more active than the dimethoxychromone derivatives
8a -e (Table 2). These data are consistent with the
observation by Nohara and co-workers11 that the presence
of hydroxyl groups on the homocyclic ring is important for
biological activity in chromone systems. While compounds
1a -d all exhibit significant cytotoxicity (LC50: 23-112
ppm), the 2-benzyl derivative 1e (LC50: 517 ppm) appears
to be even less active than the dimethoxy derivatives (LC50:
94-315 ppm). Interestingly, of all the compounds exam-
ined, 5-hydroxy-2-isopropyl-7-methoxychromone (1d) proved
to be most toxic against A. salina.
The EIMS fragmentation patterns of the monomethoxy-
chromones 1a -e and their dimethoxy analogues 8a -e
were investigated using a combination of low-resolution,
high-resolution, and B/ E linked-scan data. The fragmenta-
tion patterns proposed for 5-hydroxy-2-isopropyl-7-meth-
oxychromone 1d are outlined in Scheme 3 (Supporting
Information) and are, largely, representative of the series
1a -e. The base peak at m/z 234 corresponds to the
molecular ion Id , which appears to fragment via five major
pathways (A, B, C, D, and E). In path A, loss of a hydrogen
atom leads to the resonance-stabilized, tertiary carbocation
IId (m/z 233), decarbonylation of which affords the ring-
contracted benzofuran carbocation IVd (m/z 205). Such ring
contractions are typical of chromone derivatives.12 In path
B, loss of a methyl radical from the molecular ion gives
the resonance-stabilized, secondary carbocation fragment
IIId (m/z 219), which, like fragment IId , undergoes decar-
Gen er a l Exp er im en ta l P r oced u r es. IR spectra were
recorded on a Perkin-Elmer Spectrum 2000 FT-IR spectrom-
1
eter. The H and 13C NMR spectra were recorded in CDCl3 on
a
Bruker Avance 400 MHz NMR spectrometer and are
referenced using the solvent signals. Low-resolution mass
spectra were recorded on a Finnigan-Mat GCQ mass spec-
trometer, and high-resolution spectra were obtained on a
VG70-SEQ double-focusing magnetic sector instrument by Dr.
P. Boshoff at the Mass Spectrometry Unit, Cape Technikon,
Cape Town. The experimental procedures are illustrated by
the following examples.
P r ep a r a tion of 5-Hyd r oxy-2-isop r op yl-7-m eth oxy-
ch r om on e (1d ). A solution of 2-isopropyl-5,7-dimethoxy-
chromone (8d ; 50 mg, 0.20 mmol), Ac2O (1.01 mL, 10.7 mmol),
and HI (d 1.7; 1.52 mL, 20.2 mmol) was heated at 115 °C for
30 min. The reaction mixture was cooled and then diluted with
aqueous NaHSO3. The resulting solution was neutralized with
NaHCO3, and the precipitated solid filtered off and washed
with H2O. Flash chromatography on silica gel [elution with
hexane-EtOAc (5:1)] afforded 1d as a pale yellow solid (26
mg, 55%): mp 44-46 °C (lit.,4 40-43 °C); IR, 1H and 13C NMR,
EIMS, and HREIMS data were consistent with literature
values.4
P r ep a r a tion of 2′-Hyd r oxy-4′,6′-d im eth oxya cetop h e-
n on e (5).7 A stirred solution of 2′,4′,6′-trihydroxyacetophenone
(4; 5.0 g, 30 mmol), Me2SO4 (5.3 mL, 56 mmol), and anhydrous
K2CO3 (8.2 g, 56 mmol) in acetone (90 mL) was boiled under
reflux for 5 h. The reaction mixture was filtered and evapo-
rated in vacuo. Recrystallization of the solid residue from
petroleum ether (bp 80-100 °C)-hexane (1:9) afforded 5 as a
pale yellow solid (5.2 g, 90%): mp 75-77 °C (lit.,15 77-79 °C).
IR, 1H and 13C NMR, EIMS, and HREIMS data were consistent
with literature values.15
P r ep a r a tion of 2-Isop r op yl-5,7-d im eth oxych r om on e
(8d ). A mixture of 2′-hydroxy-4′,6′-dimethoxyacetophenone (5;
1.0 g, 5.1 mmol) and ethyl isobutyrate (3.0 mL, 22 mmol) was
added dropwise to a stirred dispersion of NaOEt [generated
in situ by adding Na metal (0.51 g, 22 mmol) to dry EtOH
(4.0 mL)]. The resulting mixture was boiled gently under reflux

1146 J ournal of Natural Products, 2003, Vol. 66, No. 8
Notes
for 8 h, during which time, a thick yellow slurry was formed.
After cooling, the reaction mixture was poured into Et2O (30
mL) and, after standing for 2 h, the sodium salt was filtered
off, washed with Et2O, and dissolved in ice-cold H2O (15 mL).
The resulting solution was acidified with HOAc and then
extracted with Et2O (3 × 30 mL). The combined ethereal
extracts were dried (MgSO4) and evaporated in vacuo to afford
a brick-red residue indicated, by 1H NMR spectroscopy, to
contain a mixture of 1-(2-hydroxy-4,6-dimethoxyphenyl)-4-
methyl-1,3-pentanedione (as an enol tautomer, formulated as
6d ) and 2-hydroxy-2-isopropyl-5,7-dimethoxychromanone (7d ),
which was used without further purification. The crude
mixture, together with glacial HOAc (5.0 mL) and concentrated
H2SO4 (0.1 mL), was boiled under reflux for 4 h. The hot
solution was poured into ice-cold H2O (20 mL), and the
resulting mixture was basified with 10% aqueous NaHCO3 (20
mL) and extracted with Et2O (3 × 50 mL). The combined
ethereal extracts were dried (MgSO4) and evaporated in vacuo
to give a light brown solid. Flash chromatography on silica
gel (elution with EtOAc) afforded 8d as a white solid (0.50 g,
Ar-C), 158.1 (s, C-8a), 162.1 (s, C-5), 165.4 (s, C-7), 168.8 (s,
C-2), and 182.5 (s, CdO); EIMS m/z 282 [M+] (100); HREIMS
m/z 282.0888 (calcd for C17H14O4, 282.0892).
2-Ben zyl-5,7-d im eth oxych r om on e (8e): brown crystal-
line solid (after chromatography, 0.90 g, 60%); mp 170-171
°C; IR (KBr) νmax 1664 (CO) cm-1; 1H NMR (CDCl3, 400 MHz)
δ 3.80 (2H, s, CH2Ph), 3.83 (3H, s, OCH3), 3.89 (3H, s, OCH3),
5.96 (1H, s, H-3), 6.30 (1H, d, J ) 2.0 Hz, H-6), 6.37 (1H, d, J
) 2.1 Hz, H-8), 7.25-7.34 (5H, m, Ar-H); 13C NMR (CDCl3,
100 MHz) δ 39.9 (t, CH2Ph), 55.6 (q, OCH3), 56.3 (OCH3), 92.7
(d, C-8), 96.0 (d, C-6), 109.0 (s, C-4a), 112.1 (d, C-3), 127.3 (d,
Ar-C), 128.8 (d, 2 × Ar-C), 129.1 (d, 2 × Ar-C), 135.0 (s,
Ar-C), 160.1 (s, C-8a), 160.9 (s, C-5), 163.8 (s, C-7), 164.8 (s,
C-2), and 177.4 (s, CdO); EIMS m/z 296 [M+] (100); HREIMS
m/z 296.1050 (calcd for C18H16O4, 296.1049).
Assessm en t of Biologica l Activity. A. salina larvicidal
bioassays were performed following the method described by
Solis et al.9 The 10% trimmed Spearman-Karber method10
was used to obtain estimates of median lethal concentrations
of A. salina mortality data from 12 solutions across concentra-
tion ranges of 200.0-10.0 µg mL-1 for compounds 1a -d ;
700.0-300.0 µg mL-1 for compound 1e, and 400.0-50.0 µg
mL-1 for compounds 8a -e.
1
40%): mp 54-56 °C; IR (KBr) νmax 1656 (CO) cm-1; H NMR
(CDCl3 400 MHz) δ 1.26 (6H, d, J ) 6.9 Hz, 2 × CH3), 2.74
(1H, q, J ) 6.8 Hz, CH), 3.86 (3H, s, OCH3), 3.91 (3H, s, OCH3),
6.00 (1H, s, H-3), 6.32 (1H, d, J ) 2.2 Hz, H-6) and 6.42 (1H,
d, J ) 2.2 Hz, H-8); 13C NMR (CDCl3, 100 MHz) δ 19.9 (q, 2 ×
CH3), 32.5 (d, CH), 55.6 (q, OCH3), 56.3 (q, OCH3), 92.6 (d,
C-8), 95.9 (d, C-6), 108.9 (d, C-3), 109.0 (s, C-4a), 160.2 (s, C-8a),
160.9 (s, C-5), 163.8 (s, C-7), 171.0 (s, C-2), and 177.9 (s,
CdO); EIMS m/z 248 [M+] (100); HREIMS m/z 248.1049 (calcd
for C14H16O4, 248.1049).
Ack n ow led gm en t. The authors thank the National Re-
search Foundation (NRF) for a postgraduate bursary (to
A.T.N.), Rhodes University for a postgraduate bursary (to
C.A.G.), and the NRF and Rhodes University for generous
financial support.
Compounds 1a ,8 8a ,8 8b,16 and 8c17 have been reported
previously. Analytical data for other, new compounds prepared
in this study are as follows.
Su p p or tin g In for m a tion Ava ila ble: Major EIMS fragmentation
pathways of 1d (Scheme 3) and 1e (Scheme 4). This material is
available free of charge via the Internet at http://pubs.acs.org.
2-E t h yl-5-h yd r oxy-7-m et h oxych r om on e (1b ): brown
solid [from hexane-EtOAc (8:2), 150 mg, 80%]; mp 101-103
Refer en ces a n d Notes
°C; IR (KBr) νmax 2975 (br, OH), 1660 (CO) cm-1 1H NMR
;
(1) For part 12, see: Kaye, P. T.; Ramaite, I. D. I. S. Afr. J . Chem. 2003,
56, 25-29.
(2) Ellis, G. P. Chromenes, Chromanones and Chromones; J ohn Wiley
and Sons: New York, 1977; p 1ff. Staunton, J . In Comprehensive
Organic Chemistry; Barton, D., Ollis, W. D., Eds.; Pergamon Press:
Oxford, 1974; Vol. 4, p 659ff.
(3) Lo´pez, J . A.; Barillas, W.; Gomez-Laurito, J .; Martin, G. E.; Al-
Rehaily, A. J .; Zemaitis, M. A.; Schiff, P. L., J r. J . Nat. Prod. 1997,
60, 24-26.
(4) Tsui, W. Y.; Brown, G. Phytochemistry 1996, 43, 871-876.
(5) Kaye, P. T.; Nchinda, A. T.; Gray, C. A. J . Chem. Res. (S) 2002, 321-
325.
(CDCl3, 400 MHz) δ 1.27 (3H, t, J ) 7.2 Hz, CH3), 2.61 (2H, q,
J ) 7.4 Hz, CH3CH2), 3.87 (3H, s, OCH3), 6.02 (1H, s, H-3),
6.32 (1H, d, J ) 2.2 Hz, H-6), 6.35 (1H, d, J ) 2.1 Hz, H-8),
12.67 (1H, s, OH); 13C NMR (CDCl3, 100 MHz) δ 10.9 (q, CH3),
27.4 (t, CH3CH2), 55.7 (q, OCH3), 92.4 (d, C-8), 97.9 (d, C-6),
105.4 (s, C-4a), 107.2 (d, C-3), 158.1 (s, C-8a), 162.2 (s, C-5),
165.4 (s, C-7), 171.5 (s, C-2), 182.7 (s, CdO); EIMS m/z 220
[M+] (100); HREIMS m/z 220.0727 (calcd for C12H12O4,
220.0736).
(6) Huang, C.; Da, S.; Li, Y.; Y. Li, Y. J . Nat. Prod. 1997, 60, 277-278.
(7) Li, H.-Y.; Nehira, T.; Hagiwara, M.; Harada, N. J . Org. Chem. 1997,
62, 7222-7227.
5-Hyd r oxy-7-m eth oxy-2-p r op ylch r om on e (1c): pale yel-
low crystalline solid (after chromatography, 125 mg, 66%); mp
1
89-91 °C; IR (KBr) νmax 2967 (br, OH), 1654 (CO) cm-1; H
(8) Mukerjee, S. K.; Seshadri, T. R.; Varadarajan, S. Proc. Indian Acad.
Sci. Sect. A 1953, 37, 127-142.
NMR (CDCl3, 400 MHz) δ 1.01 (3H, t, J ) 7.4 Hz, CH3), 1.75
(2H, m, CH3CH2), 2.55 (2H, t, J ) 7.5 Hz, CH3CH2CH2), 3.84
(3H, s, OCH3), 6.02 (1H, s, H-3), 6.32 (1H, d, J ) 2.1 Hz, H-6),
6.35 (1H, d, J ) 2.1 Hz, H-8), 12.69 (1H, s, OH); 13C NMR
(CDCl3, 100 MHz) δ 13.5 (q, CH3), 20.2 (t, CH3CH2), 36.1 (t,
CH3CH3CH2), 55.7 (q, OCH3), 92.5 (d, C-8), 97.9 (d, C-6), 105.5
(s, C-4a), 108.1 (d, C-3), 158.2 (s, C-8a), 162.2 (s, C-5), 165.4
(s, C-7), 170.3 (s, C-2), 182.6 (s, CdO); EIMS m/z 234 [M+]
(100); HREIMS m/z 234.0894 (calcd for C13H14O4, 234.0892).
2-Ben zyl-5-h yd r oxy-7-m eth oxych r om on e (1e): white
crystalline solid (from EtOH, 115 mg, 61%); mp 152-153 °C;
IR (KBr) νmax 3000 (br, OH), 1677 (CO) cm-1; 1H NMR (CDCl3,
400 MHz) 3.83 (3H, s, OCH3), 3.87 (2H, s, CH2Ph), 5.96 (1H,
s, H-3), 6.32 (1H, d, J ) 2.1 Hz, H-6), 6.34 (1H, d, J ) 2.1 Hz,
H-8), 7.26-7.37 (5H, m, Ar-H) and 12.64 (1H, s, OH); 13C
NMR (CDCl3, 100 MHz) δ 40.5 (t, CH2Ph), 55.7 (q, OCH3), 92.5
(d, C-8), 98.0 (d, C-6), 105.3 (s, C-4a), 108.9 (d, C-3), 127.5 (d,
Ar-C), 128.9 (d, 2 x Ar-C), 129.2 (d, 2 × Ar-C), 134.5 (s,
(9) Solis, P. N.; Wright, C. W.; Anderson, M. M.; Gupta, P. M.; Phillipson,
J . D. Planta Med. 1993, 59, 250-252.
(10) Hamilton, M. A.; Russo, R. C.; Thurston, R. V. Environ. Sci. Technol.
1977, 11, 714-719.
(11) Nohara, A.; Kuriki, H.; Saijo, T.; Ukawa, K.; Murata, T.; Kanno, M.;
Sanno, Y. J . Med. Chem. 1975, 18, 34-37.
(12) Brogden, P. J .; Gabbutt, C. D.; Hepworth, J . D. In Comprehensive
Heterocyclic Chemistry; Boulton, A. J ., McKillop, A., Eds.; Pergamon
Press: Oxford, 1984; Vol. 3, p 613.
(13) Dyke, S. F.; Floyd, A. J .; Sainsbury, M.; Theobald, R. S. An Introduc-
tion to Organic Spectroscopy; Penguin Books: London, 1971; p 188ff.
(14) Nchinda, A. T. Chemical Studies of Selected Chromone Derivatives.
Ph.D. Thesis, Rhodes University, Grahamstown, South Africa, 2002,
pp 81-85.
(15) Morris, J .; Wishka, D. G.; Fang, Y. Synth. Commun. 1994, 26, 849-
858.
(16) Ahluwalia, V. K.; Sunita. Indian J . Chem. Sect. B 1977, 15, 240-
241.
(17) Rideout, J . A.; Smith, I. R.; Sutherland, M. D. Aust. J . Chem. 1976,
29, 1087-1098.
NP030097D