Ceric Ammonium Sulfate (CAS) Mediated Oxidations of Benzophenones Possessing a Phenolic Substituent for the Synthesis of Xanthones and Related Products

Article abstract of DOI:10.1021/acs.joc.8b02503

Work previously published by our group described novel methodology for the synthesis of xanthones and related products from phenolic benzophenones in a reaction mediated by ceric ammonium sulfate (CAS). In this paper we further explore this novel reaction by subjecting an additional set of phenolic benzophenones to CAS to afford a range of compounds, including xanthones, 9H-xanthen-2,9(4aH)-diones, 3H-spiro[benzofuran-2,1′-cyclohexa[2,5]diene]-3,4′-diones, and biaryl compounds. A comparison of these reactions with the more commonly used oxidant ceric ammonium nitrate (CAN) was also conducted. Based on these results, greater insight into the reaction mechanism has been gained. In addition, the conversion of the synthesized xanthen-2,9(4aH)-diones to xanthones by treatment with sodium dithionite is described.

Full text of DOI:10.1021/acs.joc.8b02503

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Article
Ceric ammonium sulfate (CAS) mediated oxidations
of benzophenones possessing a phenolic substituent
for the synthesis of xanthones and related products
Jean Dam, Moira L. Bode, and Charles B. de Koning
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02503 • Publication Date (Web): 05 Dec 2018
Downloaded from http://pubs.acs.org on December 6, 2018
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Page 1 of 31
The Journal of Organic Chemistry
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Ceric ammonium sulfate (CAS) mediated oxidations of
benzophenones possessing a phenolic substituent for the
synthesis of xanthones and related products
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Jean Dam, Moira L. Bode and Charles B. de Koning*
Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050,
South Africa
AUTHOR EMAIL ADDRESS Charles.deKoning@wits.ac.za
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RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
ABSTRACT: Work previously published by our group described novel methodology for the synthesis
of xanthones and related products from phenolic benzophenones in a reaction mediated by ceric
ammonium sulfate (CAS). In this paper we further explore this novel reaction by subjecting an
additional set of phenolic benzophenones to CAS to afford a range of compounds, including xanthones,
9H-xanthen-2,9(4aH)-diones, 3H-spiro[benzofuran-2,1'-cyclohexa[2,5]diene]-3,4'-diones and biaryl
compounds. A comparison of these reactions with the more commonly used oxidant ceric ammonium
nitrate (CAN) was also conducted. Based on these results, greater insight into the reaction mechanism
has been gained. In addition, the conversion of the synthesized xanthen-2,9(4aH)-diones to xanthones
by treatment with sodium dithionite is described.
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O
O
1
2
3
4
5
6
7
8
R1 = OMe; R2 = OMe
R3 = H; R4 = H
60%
59%
24%
O
O
O
R4
O
OH
R1 = OMe; R2 = H
9
R3 = OMe, R4 = OMe
CAS
MeCN, H2O, CHCl3
O
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O
O
R3
R1
O
R2
O
OH
R1 = OMe; R2 = H
R3 = OMe, R4 = H
O
2
KEYWORDS (Word Style “BG_Keywords”). Benzophenones, ceric ammonium sulfate, oxidative
addition, xanthone, spirofuran, xanthendiones
Introduction
The remarkable biological activity of xanthones (dibenzo-γ-pyranones) has caught the attention of
medicinal and synthetic chemists. These privileged scaffolds isolated from plants, lichens and fungi
(examples in Figure 1)1,2,3 have been found to display significant antitumour,4 antioxidant,2
antimalarial,5 and anti-HIV activity.6
HO
O
OH
O
OH
OH
O
O
OH
O
HO
HO
O
O
O
O
OH
OH
OH
Bikaverin (antitumour)
BrPh3P
Mangiferin (antioxidant)
O
O
OH
O
O
O
HO
O
O
O
OH
Caged Garcinia xanthone CR135 (antimalarial)
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The Journal of Organic Chemistry
Figure 1 – A selection of naturally occurring xanthones
1
2
3
4
As a result many synthetic approaches to the assembly of the xanthone core have been developed.2,7
In our laboratories a new method for the synthesis of xanthones and related compounds was disclosed in
2010.8 We reported that in the presence of ceric ammonium nitrate (CAN) phenolic-containing
benzophenones could undergo an oxidative cyclization to form xanthones and related products.
However, after further experimentation it was ascertained that the reagent was ceric ammonium sulfate
(CAS) and not ceric ammonium nitrate (CAN). A correction has been made to the Journal of Organic
Chemistry manuscript (DOI: 10.1021/jo101873v).
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In this paper we report further findings on the use of CAS as a reagent for the preparation of
xanthones and related compounds. Based on the results of the additional examples we further speculate
on the mechanism of the reaction. In addition, the conversion of some of the xanthen-2,9(4aH)-diones
into xanthones by treatment with sodium dithionite is described.
Results and Discussion
As a starting point we repeated the same reactions described in the Journal of Organic Chemistry
paper8 utilizing a recently purchased commercial source of CAS. Subjecting benzophenones 1-5 to
optimized reaction conditions of between 3 and 4 equivalents of CAS (repeated in triplicate) afforded
products 6-12 as shown in Table 1.8 As before, and depending on the nature of the benzophenone the
CAS-mediated oxidative cyclization reaction afforded a variety of products; including xanthones 6, 9
and 10, and 9H-xanthen-2,9(4aH)-diones 7, 8, 11 and 12. These were the same products as described in
the Journal of Organic Chemistry Note. However; some of the yields under these optimized reaction
conditions were different to those previously described.8
Table 1 – CAS mediated oxidative cyclizations
Benzophenone
Product(s) and yield
O
O
OH
O
O
O
O
O
O
O
O
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1
2
6 (30 %)
7 (45 %)
1
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7
8
O
O
O
O
O
OH
O
O
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8 (81 %)
O
O
OH
O
O
O
O
O
O
3
9 (70 %)
O
O
O
OH
O
O
O
Cl
O
Cl
O
O
O
Cl
4
10 (28 %)
11 (50 %)
O
O
O
O
OH
Cl
O
Cl
O
O
5
12 (84 %)
a Reaction Conditions: CAS (3 to 4 eq), MeCN/H2O/CHCl3, rt, 18 h
Since CAS is rarely used in organic synthesis, we repeated the first three reactions in Table 1 using
CAN as the reagent (Table 2). Different results, in particular the yields, were obtained using CAN as the
oxidant. Exposing 1 to CAN furnished 7 exclusively in a poor yield of 16% Naphthalene 2 was
converted into 8, but in a meagre yield (26%). The third reaction with CAN (3 → 13) gave a different
product as to when CAS was used as the oxidant, albeit in a poor yield. These results demonstrate that
CAS was a superior oxidant to CAN for these transformations.
Table 2 – CAN mediated oxidative cyclizations
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The Journal of Organic Chemistry
Benzophenone
Product
1
2
3
4
O
O
O
OH
O
5
6
7
8
O
O
O
7 (16%)
9
1
10
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28
29
O
O
O
OH
O
O
O
O
O
8 (26%)
2
3
O
OH
O
O
O
O
O
O
O
13 (13%)
a Reaction Conditions: CAN (3-5 eq), MeCN/H2O/CHCl3, rt, 10 mins
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At the time of the original publication8 the major product i.e. xanthones (e.g. 6) or diones (e.g. 8) from
the reaction could not be rationally predicted. A tentative mechanism (Scheme 1) was proposed in an
attempt to explain the results,8 in which the benzophenone would initially form a radical cation 14a
from 1, which then allowed for the formation of 15. This was proposed as it was in line with the
mechanism suggested for the oxidation with CAN of para-dimethoxybenzenes to quinones.9
Intermediate radical 15 could aromatize to form the xanthone 6, although the loss of a methoxy radical
seemed problematic in the conversion of 15 into 6. Alternatively, the intermediate radical 15 could be
converted into the dione 7 by reaction with a further equivalent of CAS in the presence of water.
However, since only benzophenones possessing at least two methoxy substituents (with one ortho to the
ketone bridge) on the benzene ring of the benzophenone lacking the phenol were investigated, this
mechanism was speculative.
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O
O
O
O
O
1
2
3
4
5
6
7
O
HO
6
1
- OMe
8
9
O
O
O
O
10
11
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O
O
O
Ce(IV)
O
HO
O
O
O
7
14a
15
Scheme 1 – Previously proposed mechanism for the oxidative formation of xanthones
In order to gain a better understanding of the novel CAS reaction, a further set of benzophenones 16-
21 containing a range of aromatic methoxy substitution patterns were synthesized from 22a-f. This was
achieved using methodology previously reported8 by subjecting the substituted benzenes 22b-f to n-
butyllithium (or magnesium turnings in the case of 22a) and benzyl 2-(benzyloxy)benzoate (or 2-
(benzyloxy)benzaldehyde for 22a) (Scheme 2) to afford ketones 23a-f. Treatment of 23a-f with
hydrogen gas and palladium supported on carbon resulted in the desired benzophenones 16-21
containing a hydrogen-bonded phenol substituent.
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The Journal of Organic Chemistry
R1
R6
O
OBn
Entry
R2
R3
H
R4
H
R5
H
R6
H
R1
Br
1
2
3
4
5
6
7
8
i) n-BuLi, THF
OR Mg, THF (
R6
R5
R2
R3
R5
R4
a
OMe
22a
)
O
b
c
H
OMe OMe
H
H
H
H
ii)
R2
OBn
OBn
Br
OMe
H
H
H
OMe
OMe
R4
R3
Yield (%)
22a-f
d
Br OMe
OMe
H
H
H
23a
77
43
45
92
81
44
OR
23b
23c
23d
23e
23f
e
f
OMe
H
H
H
OMe
H
H
CHO
9
22a
(
)
OMe OMe
Br
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11
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13
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21
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37
OBn
O
OH
O
OH
O
O
O
OH
O
O
O
O
10 % Pd/C, H2
MeOH
18 (74%)
OH
16 (85%)
17 (66%)
O
O
O
OH
O
O
OH
O
O
O
O
21 (62%)
20 (60%)
19 (71%)
Scheme 2 – The synthesis of additional phenolic-containing benzophenones.
The phenol containing benzophenones 16-21 were exposed to 2-4 equivalents of CAS for 12 h. Each
reaction mixture was analysed by TLC and, where possible, new compounds formed from the reaction
were isolated and characterized. The reactions were performed in triplicate for each substrate to ensure
reproducibility and the yields are reported averages (Table 3). Unfortunately, while all the mono-
methoxybenzophenone 16 was consumed during the reaction, nothing from the reaction could be
successfully characterized. ortho-Dimethoxybenzophenone 17 resulted in the synthesis of xanthone 24.
Trimethoxybenzophenone 18 allowed for the formation of the novel spirofuran 25. The three remaining
dimethoxybenzophenones 19-21 afforded the unexpected novel biaryl dimers 26, 27 and 28
respectively, albeit in low yields.
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Table 3 – Products resulting from exposing benzophenones 16-21 to CAS for 18 h
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Average
Yield
of
1
2
3
4
Benzophenone
16
Product
None
triplicate experiments
-
5
6
7
O
8
9
10
11
12
13
14
15
16
17
18
19
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21
22
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58
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60
17
60%
O
O
24
O
O
O
O
O
18
59%
25
O
O
OH
O
O
19
24%
O
O
OH
26
O
O
OH
O
O
20
18%
O
O
OH
27
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The Journal of Organic Chemistry
O OH
1
2
O
3
4
5
6
7
O
O
21
15%
8
9
O
O
OH
10
11
12
13
14
15
16
17
18
28
The structures of the dimers 26-28 were initially determined from NMR spectroscopic and HRMS
data and the structure of 26 was later confirmed by obtaining the X-ray crystal structure (details
available in the supplementary information). While the formation of these dimers was an unexpected
result and unprecedented under these conditions, related dimers have been reported under oxidative
CAN conditions.10,11
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Combining the results previously obtained8 and repeated under optimal conditions as shown in Table
1 with the new results obtained in Table 3 has allowed us to examine more fully the scope and
limitations of the CAS-mediated reaction, as well as speculate on a more defined mechanism.
Firstly, for the CAS-mediated reaction to take place resulting in the formation of xanthones (e.g. 24)
diones, (e.g. 12) or spiro-containing compounds (e.g. 25) at least two aromatic methoxy substituents are
required on the electron-rich benzene ring to assist in the formation of radical cations such as 14a
(Scheme 3). In addition, one of the methoxy substituents needs to be situated ortho to the ketone bridge
and the second methoxy substituent needs to be situated either ortho (e.g. 17 → 24) or para (e.g. 1 → 6
+7) to the first methoxy substituent on the same aromatic ring. Thus, we propose that oxidation of the
benzophenone 1 occurs as shown in the example in Scheme 3 to afford the previously proposed radical
cation 14a. The oxidation of the electron-rich aromatic ring of 1 to afford the radical cation 14a is
expected as a result of evidence provided by ESR and UV spectroscopic measurements in the single
electron transfer oxidation (SET) of 1,4-dimethoxybenzene.12 In addition, it has often been speculated13
that with electron rich aromatic compounds SET oxidations take place to afford aromatic radical cations
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similar to 14a. However, we cannot rule out the possibility of the reaction proceeding by way of the
related phenoxy radical 14b, particularly as the reactions of 19-21 lead to biaryl compounds that must
be formed from oxidative coupling of the phenols.
1
2
3
4
5
6
7
8
9
Subsequent addition of the phenol of 14a to the methoxy-containing radical cation benzene ring
would afford the resonance stabilized ring closed radical intermediate 29 where the para positioned
methoxy substituent of 29 provides further stabilization of the radical. If the reaction proceeds via the
oxygen-centred radical 14b, the key cyclization step would be homolytic in nature and would result in a
cationic intermediate equivalent to radical 29. In order for the intermediate 29 to regain aromaticity, to
allow for the formation of xanthone 6, formally the loss of a methoxy radical would have to take place.
For this to occur, the driving force for reforming the aromatic ring would facilitate the process.
Alternatively, reduction of the radical 29, by oxidation of another molecule of 1 in the presence of a
proton source would lead to the formation of enol 30. Spontaneous elimination of methanol from 30
would allow for the formation of xanthone 6. Alternatively, the ring closed intermediate 29 could
undergo a further oxidation to afford the dione 7, via the oxocarbenium ion, followed by the addition of
water as shown in Scheme 3.
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13
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15
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22
23
24
25
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O
O
O
O
O
O
Ce+4
 H
 1e
O
O
O
O
O
O
H
14a
H
29
1
O
O
OH
O
O
Ce+4
)
1e
 MeOH
+ 1e
+ H
+ H2O
O
O
 H
6
30
 MeOH
O
O
O
O
O
O
O
O
7
14b
Scheme 3 – Proposed mechanism for the formation of xanthone 6 and dione 7
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Alternatively, with the 1,3,5-trimethoxy-containing aromatic compound 18, phenol addition, or
1
2
phenoxy radical addition, to the radical cation 31 would result in radical intermediate 32, which could
be further stabilized through resonance by all three aromatic methoxy substituents (Scheme 4). Further
oxidation of 33 followed by the addition of water, as before, would result in the formation of spirofuran
25. It must be noted that in order for the spirofuran to form three aromatic methoxy substituents are
required. This was also shown to be the case in the JOC Note we previously published.8
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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28
29
30
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O
O
O
O
Ce+4
 H
O
O
O
HO
O
O
H
18
31
O
O
O
O
O
O
O
O
O
O
33
32
O
O
O
O
O
Ce+4
O
O
O
O
O
25
Scheme 4 – Proposed mechanism for the formation of spirofuran 25
Finally, the formation of the biaryl para-dimers 26-29 must occur by means of a classical oxidative
phenoxy radical-mediated dimerization process from the corresponding phenols 21-23, albeit in low
yields. Clearly, the mechanistic rationale for this transformation would require an intermediate phenoxy-
type radical, analogous to 14b. In these examples, as the second methoxy substituent is not ortho or
para to the methoxy substituent situated ortho to the ketone bridge the formation of xanthones or diones
does not take place. In these reactions we were unable to detect or isolate any of the ortho-coupled
biaryl dimers. However, we cannot exclude the formation of these types of products, or possibly
products that would react further to form polymeric-type materials.
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The unique dione structures of 7, 8, 11 and 12 are not naturally occurring scaffolds, however, they are
structurally similar to the xanthone core. We therefore wished to develop methodology that could be
used to transform these diones into their xanthone counterparts. Treatment of diones, 7, 8, 11 and 12
with sodium dithionite in a THF/H2O suspension at room temperature afforded the hydroxy-containing
xanthones 34a-d as shown in Scheme 5.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
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39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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59
60
O
O
O
R2
HO
R1
R2
Na2S2O4
THF/H2O
O
O
O
R1
34a-d
R1
R2
H
R1
a H
b H
c naphthyl H
d naphthyl Cl 68%
R2 Yield
90%
Cl 75%
64%
7
H
H
H
11
8
Cl
naphthyl H
naphthyl Cl
12
Scheme 5 – Conversion of diones to xanthones
Conclusion
In conclusion, we have further expanded upon the novel ceric ammonium sulfate (CAS) oxidative
cyclization reaction developed in our labs. Although debatable, we believe that the first oxidation takes
place on the more electron rich aromatic ring containing at least two aromatic methoxy substituents.
Once the aromatic radical cation is formed this allows for the phenolic oxygen's lone pair or the
phenoxy radical on the adjacent aromatic ring to add to the radical cation forming a new carbon-oxygen
bond. Depending on the electronic nature of the benzophenone and the arrangement of the methoxy
substituents, a variety of products are isolated including xanthones, 9H-xanthen-2,9(4aH)-diones, 3H-
spiro[benzofuran-2,1'-cyclohexa[2,5]diene]-3,4'-diones, as well as the dimers 26, 27 and 28.
Further details of this oxidative mechanism have also been outlined. In summary, the xanthone and
dione products require at least one methoxy substituent to allow for stabilization in the intermediate
radical (for example, structure 29) as in the formation of products 6 and 24 from 1 and 17 respectively.
Utilizing hydroxyl benzophenones 19 and 20 does not allow for further stabilization of the intermediate
radical by the aromatic methoxy substituents and results in the formation of dimers 26 and 27. While
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starting material 21 does possess a suitably positioned aromatic methoxy substituent, it does not bear an
aromatic methoxy group at the site of nucleophilic attack. Hence exposure of 21 to CAS results in the
formation of the biaryl compound 28. Finally, the spiro-containing product 25 is formed as each of the
three aromatic methoxy substituents allow for stabilization of the radical as shown in Scheme 4 which is
uniquely present in starting material 18.
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In addition, it has been shown that CAS is superior to CAN for these types of transformations. In fact
based on the yields for the oxidation reactions mediated by CAN it is clear that it is not a suitable
reagent for these transformations. Furthermore, we have shown that the novel diones 7, 8, 11 and 12
could be converted into xanthones 34a-d under reductive conditions.
Experimental
The solvents and reagents used for this project were purchased from ACE Chemicals or Sigma-
Aldrich and used without purification unless otherwise stated. Acetonitrile (MeCN) was distilled over
calcium hydride under nitrogen gas. Tetrahydrofuran (THF) was distilled over sodium wire and
benzophenone under nitrogen gas. Thin layer chromatography (TLC) was performed on aluminium-
backed ALUGRAM Sil G/UV254 plates that are pre-coated with 0.25 mm silica gel 60. The compounds
were detected using ultraviolet light. Flash column chromatography was performed using silica gel
(particle size 0.035-0.070 mm). 1H NMR spectra were recorded on spectrometers operating at 500 MHz
and 300 MHz respectively. All spectra were recorded in deuterated chloroform (CDCl3), deuterated
methanol (CD3OD) and deuterated dimethyl sulfoxide (d6-DMSO) with all chemical shift values
reported in parts per million referenced against 0.03% tetramethylsilane (TMS) as an internal standard.
Coupling constants, J, are reported in Hertz (Hz). Commonly used abbreviations in assignments include:
13
s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. 75.47 MHz and 125 MHz C NMR (1H
decoupled) spectra were recorded either at 75 MHz or 126 MHz. All spectra were recorded in CDCl3,
CD3OD or d6-DMSO and the chemical shifts are reported on the δ scale in parts per million (ppm)
relative to the central signal of CDCl3 taken as 77.0 ppm, CD3OD as 49.0 ppm and d6-DMSO as 39.5
ppm. Infrared spectra were recorded where all predominant absorptions are reported in terms of
wavenumbers (ν/cm-1). IR spectra were obtained only for compounds where no IR data was available
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and for final compounds. High resolution mass spectra (HRMS) were recorded and quoted in relative
abundance (m/z). HRMS was performed only on novel compounds where no MS data was available as
well as for final compounds. Melting points were recorded and are reported without correction. Single
crystal X-ray diffraction data were collected on a CCD area detector diffractometer with graphite
monochromated Mo K α-radiation (50kV, 30mA) using the APEX 2 data collection software. The
collection method involved ω-scans of width 0.5° and 512x512 bit data frames. Data reduction was
carried out using the program SAINT+ version 6.02.6 software and SADABS was used to make
empirical absorption corrections.14 SHELXS-97 was used to solve crystal structures by direct methods.14
After initial isotropic refinements of non-hydrogen atoms, further anisotropic refinements were done by
full matrix least-squares calculations based on F2 using SHELXL-97.14 C-bound H atoms were first
located in the difference map, then positioned geometrically and allowed to ride on their respective
parent atoms, with thermal displacement parameters 1.2 times of the parent C atom. Where possible, the
coordinates and isotropic displacement parameters of the N‒bound and O‒bound H atoms involved in
the hydrogen bonding interactions were allowed to refine freely. Diagrams and publication material
were generated using WinGX15 and ORTEP-3 and the displacement ellipsoids shown at a 50%
probability level.16
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General experimental procedure for the Ceric Ammonium Sulfate (CAS) mediated oxidation of
benzophenones 1-5, and 16-21. A CHCl3 and MeCN solution (1:4 v/v) was used to dissolve the phenol-
containing benzophenone derivatives. Once the benzophenone had completely dissolved, water (double
the volume than that of the CHCl3) was added and a suspension resulted. CAS۰2H2O (2-4 eq) was
added slowly and the suspension stirred at room temperature overnight. The mixture was then
transferred to a separating funnel and EtOAc and water added. The water layer was run off and the
organic layer was washed further with sat NaHCO3 and brine, dried over anhydrous Na2SO4
concentrated in vacuo and purified by column chromatography to afford products 6-12 as described
previously8 but in the yields shown in Table 1. In addition, products 24-28 were also isolated.
2-Methoxy-9H-xanthen-9-one (6) and 4a-methoxy-2H-xanthene-2,9(4aH)-dione (7). The general
procedure was followed using (2,5-dimethoxyphenyl)(2-hydroxyphenyl)methanone, (1) (0.400 g, 1.688
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The Journal of Organic Chemistry
mmol) and CAS۰2H2O (3.350 g, 5.296 mmol, 3.14 eq). Purification using flash column chromatography
10-20 % EtOAc/Hexane resulted in a white solid and yellow crystals being collected. Using NMR
spectroscopy, the white powder was determined to be 2-methoxy-9H-xanthen-9-one, 6 (0.142 g, 36 %)
and the yellow crystals to be 4a-methoxy-2H-xanthene-2,9(4aH)-dione, 7 (0.153 g, 36 %). *Note: the
yields reported in the experimental were obtained for a single experiment, while the yields reported in
Table 1 were the average yields obtained over at least three experiments.
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2-Methoxy-9H-xanthen-9-one (6). M.p. = 127-128 °C, lit 131-133 °C.8 1H NMR (300 MHz,
CDCl3): δH = 8.36 (1H, dd, J = 8.0 and 1.7 Hz), 7.76 – 7.68 (2H, m), 7.49 (1H, dd, J = 8.5 and 1.2 Hz),
13
7.45 (1H, d, J = 9.1 Hz), 7.41 – 7.37 (1H, m), 7.37 – 7.33 (1H, m), 3.93 (3H, s); C{H} NMR (75
MHz, CDCl3): δC = 177.1, 156.1, 156.0, 151.0, 134.6, 126.7, 124.9, 123.7, 122.2, 121.3, 119.4, 118.0,
105.9, 55.9; IR νmax.(cm-1) = 2972, 2938, 2868, 2851, 1670, 1636, 1601, 1462, 1288, 1236, 1219, 1202,
1150, 1097, 1045, 1028, 1011, 959, 941, 854, 820, 785, 750, 698, 629. 4a-Methoxy-2H-xanthene-
2,9(4aH)-dione (7). M.p. = 108-110 °C, 110-112 °C.8 1H NMR (300 MHz, CDCl3): δH = 8.02 (1H, dd,
J = 7.9 and 1.8 Hz), 7.60 (1H, ddd, J = 8.3, 7.3 and 1.7 Hz), 7.18 (1H, ddd, J = 8.0, 7.3 and 1.1 Hz),
7.14 – 7.07 (2H, m), 6.89 (1H, d, J = 2.0 Hz), 6.44 (1H, dd, J = 10.4 and 2.0 Hz), 3.35 (3H, s). 13C{H}
NMR (75 MHz, CDCl3): δC = 185.0, 180.9, 157.0, 144.5, 140.1, 137.0, 130.7, 128.5, 127.5, 123.3,
121.7, 118.5, 95.1, 51.3; IR νmax.(cm-1) = 2972, 2938, 2868, 2851, 1670, 1636, 1601, 1462, 1288, 1236,
1219, 1202, 1150, 1097, 1045, 1028, 1011, 959, 941, 854, 820, 785, 750, 698, 629.
12a-Methoxy-5H-benzo[c]xanthene-5,7(12aH)-dione
(8).
(1,4-Dimethoxynaphthalen-2-yl)(2-
hydroxyphenyl)methanone 2 (0.120 g, 0.434 mmol) in a 4:2:1 MeCN:H2O:CHCl3 solvent mixture was
exposed to CAS۰2H2O (0.824 g, 1.303 mmol, 3.00 eq) for 18 h. After purification by flash column
chromatography in 20 % EtOAc/Hexane, an orange solid resulted. NMR spectroscopy was used to
confirm the identity of 12a-methoxy-5H-benzo[c]xanthene-5,7(12aH)-dione, 8 (0.092 g, 73 %). M.p. =
139-140 °C, lit 162-165 °C.8 1H NMR (500 MHz, CDCl3): δH = 8.15 (1H, dd, J = 7.9 and 1.4 Hz), 8.03
(2H, m), 7.80 (1H, td, J = 7.6 and 1.4 Hz), 7.62 (2H, m), 7.19 (1H, d, J = 1.4 Hz), 7.19 – 7.16 (2H, m),
13
3.03 (3H, s); C{H} NMR (75 MHz, CDCl3): δC = 184.0, 180.9, 157.7, 143.7, 137.0, 136.6, 133.9,
130.8, 130.6, 130.2, 127.5, 126.9, 126.5, 123.2, 121.5, 118.6, 96.4, 51.3; IR νmax.(cm-1) = 3069, 2936,
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2833, 1726, 1691, 1666, 1607, 1458, 1387, 1294, 1267, 1219, 1134, 1103, 1067, 1016, 943, 870, 756,
737, 702, 660; ESI-MS TOF (m/z) calculated [M+H]+ for C18H13O4 293.0814, found 293.0811.
2,3-Dimethoxy-9H-xanthen-9-one (9). Following the general procedure, (2-hydroxyphenyl)(2,4,5-
trimethoxyphenyl)methanone 3 (0.167 g, 0.579 mmol) exposed to CAS۰2H2O (1.466 g, 2.317 mmol,
4.00 eq) resulted in a single product that was determined to be 2,3-dimethoxy-9H-xanthen-9-one 9. This
was collected as yellow crystals (0.122 g, 69 %). M.p. = 153-155 °C, lit 170-172 °C.8 1H NMR (300
MHz, CDCl3): δH = 8.35 (1H, ddd, J = 8.0, 1.8 and 0.5 Hz), 7.74 – 7.65 (2H, m), 7.47 (1H, ddd, J = 8.5,
1.1 and 0.5 Hz), 7.38 (1H, ddd, J = 8.2, 7.1 and 1.1 Hz), 6.93 (1H, s), 4.03 (3H, s), 4.01 (3H, s); 13C{H}
NMR (75 MHz, CDCl3): δC = 176.1, 156.1, 155.5, 152.5, 146.8, 134.0, 126.6, 123.8, 121.6, 117.7,
115.0, 105.5, 99.7, 56.5, 56.4; IR νmax.(cm-1) = 2972, 2938, 2868, 2833, 1653, 1601, 1514, 1462, 1427,
1306, 1271, 1236, 1201, 1132, 1063, 1028, 1011, 941, 854, 820, 785, 750, 698, 646.
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2-Chloro-7-methoxy-9H-xanthen-9-one (10) and 7-chloro-4a-methoxy-2H-xanthene-2,9(4aH)-
dione (11). When exposed to CAS۰2H2O (2.644 g, 4.180 mmol, 4.00 eq), (5-chloro-2-
hydroxyphenyl)(2,5-dimethoxyphenyl)methanone, 4 (0.306 g, 1.045 mmol) was transformed into two
products. The two products were separated by flash column chromatography and collected as a light
pink solid that was found to be 2-chloro-7-methoxy-9H-xanthen-9-one, 10 (0.027 g, 26 %) and a yellow
solid that was found to be 7-chloro-4a-methoxy-2H-xanthene-2,9(4aH)-dione, 11 (0.114 g, 40 %).
2-Chloro-7-methoxy-9H-xanthen-9-one (10). M.p. = 171-172 °C, lit 130-133 °C.8 1H NMR (300
MHz, CDCl3): δH = 8.31 (1H, d, J = 2.6 Hz), 7.69 (1H, d, J = 3.2 Hz), 7.65 (1H, dd, J = 8.9 and 2.6 Hz),
13
7.45 (2H, dd, J = 9.0 and 6.2 Hz), 7.35 (1H, dd, J = 9.1 and 3.1 Hz), 3.92 (3H, s); C{H} NMR (75
MHz, CDCl3): δC = 176.0, 156.3, 154.4, 150.9, 134.7, 129.5, 126.0, 125.3, 122.1, 121.8, 119.7, 119.5,
105.8, 56.0; IR νmax.(cm-1) = 3071, 2980, 2953, 2853, 1655, 1612, 1485, 1462, 1445, 1364, 1292, 1242,
1209, 1144, 1123, 1107, 1024, 993, 904, 872, 814, 785, 719, 687, 629.
7-Chloro-4a-methoxy-2H-xanthene-2,9(4aH)-dione (11). M.p. = 143-144 °C, 122-124 °C.8 1H
NMR (300 MHz, CDCl3): δH = 7.97 (1H, d, J = 2.7 Hz), 7.54 (1H, dd, J = 8.7 and 2.7 Hz), 7.08 (2H,
dd, J = 9.5 and 8.7 Hz), 6.89 (1 H, d, J = 2.0 Hz), 6.45 (1H, dd, J = 10.4 and 2.0 Hz), 3.35 (3H, s);
13C{H} NMR (75 MHz, CDCl3): δC = 184.7, 180.0, 155.4, 143.8, 139.7, 136.7, 130.9, 129.0, 129.0,
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126.9, 122.6, 120.2, 95.3, 51.4; IR νmax.(cm-1) = 3071, 3005, 2945, 2831, 1668, 1643, 1603, 1468, 1422,
1288, 1267, 1203, 1142, 1099, 1003, 945, 837, 821, 779, 714, 677.
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9
9-Chloro-12a-methoxy-5H-benzo[c]xanthene-5,7(12aH)-dione (12). The general procedure was
followed using (5-chloro-2-hydroxyphenyl)(1,4-dimethoxynaphthalen-2-yl)methanone, 5 (0.183 g,
0.534 mmol) and CAS۰2H2O (1.351 g, 2.136 mmol, 4.00 eq) resulting in the formation of 9-chloro-12a-
methoxy-5H-benzo[c]xanthene-5,7(12aH)-dione, 12. This was collected as a yellow solid (0.146 g, 84
%). M.p. = 158-160 °C, lit 162-165 °C.8 1H NMR (300 MHz, CDCl3): δH = 8.16 (1H, ddd, J = 7.8, 1.4
and 0.6 Hz), 8.03 – 7.97 (2H, m), 7.81 (1H, ddd, J = 7.9, 7.4 and 1.4 Hz), 7.63 (1H, td, J = 7.6 and 1.3
Hz), 7.56 (1H, dd, J = 8.8 and 2.7 Hz), 7.21 (1H, s), 7.19 – 7.13 (1H, m), 3.02 (H, s); 13C{H} NMR (75
MHz, CDCl3): δC = 183.7, 180.1, 156.2, 143.0, 136.7, 136.2, 134.0, 131.1, 130.8, 130.4, 128.9, 127.0,
126.9, 126.5, 122.4, 120.2, 96.7, 51.4; IR νmax.(cm-1) = 3109, 2974, 2936, 2820, 1682, 1663, 1624,
1605, 1470, 1412, 1258, 1200, 1142, 1123, 1065, 1026, 987, 949, 891, 833, 775, 737, 718, 679, 660,
621.
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General experimental procedure for the Ceric Ammonium Nitrate (CAN) mediated oxidation of
benzophenones 1-3. A CHCl3 and MeCN solution (1:4 v/v) was used to dissolve the phenol-containing
benzophenone derivatives. Water (half the volume of the acetonitrile) was used to dissolve the CAN (3-
5 eq) and this was added dropwise to the rapidly stirring solution at rt. After 10 mins, TLC analysis of
the reaction mixture showed no more starting material remained and the reaction was quenched with aq.
NaHCO3. The resulting precipitate was filtered off and washed with EtOAc and the filtrate transferred
to a separating funnel. Further portions of EtOAc and water added to the separating funnel, the organic
layer collected and dried over anhydrous Na2SO4. After concentration in vacuo, the mixture was
purified by column chromatography to afford products 7, 8 and 13.
4a-methoxy-2H-xanthene-2,9(4aH)-dione (7). The general procedure was followed using (2,5-
dimethoxyphenyl)(2-hydroxyphenyl)methanone, (1) (0.100 g, 0.387 mmol) and CAN (1.058 g, 1.936
mmol, 5.0 eq). Purification using flash column chromatography 10-20 % EtOAc/Hexane resulted in
yellow crystals being collected that were found to be 7 (0.015 g, 16 %).
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12a-Methoxy-5H-benzo[c]xanthene-5,7(12aH)-dione
(8).
(1,4-Dimethoxynaphthalen-2-yl)(2-
1
2
3
4
5
6
7
8
9
hydroxyphenyl)methanone 2 (0.200 g, 0.642 mmol) and CAN (1.052 g, 1.927 mmol, 3.0 eq) were
combined according to the general procedure. The orange solid that was found to be 8 (0.048 g, 26 %).
2′′,5-Dimethoxy-3H-spiro[benzofuran-2,1′-cyclochexa[2,5]diene]3,4′-dione (13). Benzophenone 3
(0.260 g, 0.902 mmol) in MeCN (15 ml) and CAN (1.711 g, 2.706 mmol, 3.0 eq) were combined
following the general procedure. After 10 mins no starting material was observed on the TLC plate and
a new spot was evident. After the work up procedure, drying over anhydrous Na2SO4 and concentration
in vacuo the product was purified by flash column chromatography with 10-20 % EtOAc/Hexane as the
eluent. A white solid was collected (0.036 g, 13 %) and determined to be 13 following characterization
by NMR spectroscopy. M.p. = 103-105 °C. 1H NMR (300 MHz, CDCl3): δH = 7.77 – 7.67 (2H, m, H-5
and H-7), 7.26 – 7.21 (1H, m, H-4), 7.18 (1H, ddd, J = 7.9, 7.2 and 0.8 Hz, H-6), 5.77 (1H, s, H-12),
5.20 (1H, s, H-9), 3.69 (3H, s, H-14), 3.68 (3H, s, H-15); 13C{H} NMR (75 MHz, CDCl3): δC = 195.4,
181.3, 172.5, 168.0, 153.3, 139.0, 125.7, 122.7, 119.9, 113.9, 104.0, 103.0, 86.1, 56.6, 55.6: IR (νm.cm-
1) = 3063, 2938, 2852, 1719, 1666, 1643, 1601, 1506, 1456, 1402, 1337, 1261, 1205, 1171, 1099, 1084,
1032, 991, 924, 887, 850, 750, 706, 629; ESI-MS TOF (m/z) calculated [M+H]+ for
C15H13O5 273.0757, found 273.0650.
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(2-Hydroxyphenyl)(2-methoxyphenyl)methanone (16).17 In a 2-neck round bottomed flask, dry
magnesium (0.183g, 7.54 mmol, 1.60 eq) was weighed out and a stirrer bar added, followed by a rubber
septum and condenser. The entire chamber was then evacuated, further dried under evacuation and the
chamber filled with nitrogen (repeated 3 times). Once filled with nitrogen for the final time, THF (5 ml)
was injected followed by the 2-bromoanisole (1.32 g, 7.07 mmol, 1.50 eq). Heat was applied as
necessary to initiate the Grignard reagent formation and then the reaction left to stir until all the
magnesium was consumed (approximately 30 min) under a nitrogen atmosphere. To the brown solution,
a further 5 ml of THF was added and cooled to 0 °C. 2-(Benzyloxy)benzaldehyde (1.00 g, 4.71 mmol)
was dissolved in THF (5 ml) and injected dropwise into the cooled Grignard solution. An immediate
color change is observed and a bright yellow color developed while the reaction was left to stir at 0 °C
for 2 h. 1M HCl (10 ml) was added to the reaction with vigorous stirring for 10 min, the suspension
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transferred to a separation funnel and the aqueous layer removed. The organic layer was further washed
with brine before being dried with anhydrous MgSO4 and concentrated in vacuo. The product was then
purified by column chromatography with using 10-20 % EtOAc/Hexane as the eluent and (2-
(benzyloxy)phenyl)(2-methoxyphenyl)methanol was collected as a yellow oil (1.48 g, 99 %). 1H NMR
(300 MHz, CDCl3): δH = 7.38 – 7.20 (7H, m), 7.18 (1H, dd, J = 7.5 and 1.7 Hz), 7.00 – 6.90 (2H, m),
6.87 (2H, d, J = 7.7 Hz), 6.43 (1H, d, J = 5.5 Hz), 5.05 (2H, d, J = 3.8 Hz), 3.77 (3H, s), 3.35 (1H, d, J =
1
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5.4 Hz); C{H} NMR (75 MHz, CDCl3): δC = 156.9, 155.8, 136.9, 131.6, 131.2, 128.5, 128.3, 127.9,
127.9, 127.8, 127.33, 120.8, 120.6, 111.7, 110.5, 70.1, 67.3, 55.4; IR νmax.(cm-1) = 3560, 3442, 3030,
2940, 2839, 1601, 1488, 1449, 1381, 1287, 1238, 1105, 1015, 870, 745, 695, 651; ESI-MS TOF (m/z)
calculated [M+Na]+ for C21H20O3Na 343.1310, found 343.1302. In a round bottomed flask, (2-
(benzyloxy)phenyl)(2-methoxyphenyl)methanol,18 (1.00 g, 4.71 mmol, 1 eq) was dissolved in 20 ml
CH2Cl2. To this solution 1.00 g of flash chromatography silica was added followed by PCC (1.49 g,
6.92 mmol, 1.5 eq) in portions. This reaction mixture was stirred under nitrogen for 2 h, a thick brown
by product results as the reaction progresses. Once the reaction is completed (as determined by TLC)
the reaction was filtered through a glass fritted funnel lined with Celite and flash silica and this plug
washed with EtOAc. The filtrate was concentrated in vacuo and the resulting product (2-
(benzyloxy)phenyl)(2-methoxyphenyl)methanone 23a collected as a viscous yellow oil (1.131 g, 77 %)
1
used with no further purification. H NMR (300 MHz, CDCl3): δH = 7.60 (1H, dd, J = 7.6 and 1.8 Hz,
7.52 (1H, dd, J = 7.6 and 1.8 Hz), 7.40 (2H, m), 7.22 – 7.17 (3H, m), 7.07 – 7.00 (1H, m), 7.00 – 6.90
13
(4H, m), 6.82 (1H, dd, J = 8.4 and 0.9 Hz), 4.93 (2H, s), 3.59 (3H, d, J = 0.6 Hz); C{H} NMR (75
MHz, CDCl3): δC = 195.5, 158.3, 157.2, 136.4, 132.6, 132.5, 130.9, 130.6, 130.4, 130.3, 128.2, 127.4,
126.7, 120.8, 120.3, 112.4, 111.6, 70.1, 55.6; IR νmax.(cm-1) = 3027, 2944, 2837, 1642, 1596, 1484,
1446, 1382, 1308, 1248, 1161, 1103, 1022, 924, 853, 750, 695, 638. Benzophenone 23a (1.131 g, 3.716
mmol) and 10 % Pd/C (0.113 g, 10 mass %) in 30 ml of MeOH under a H2 atmosphere resulted in the
formation of benzophenone 16 (0.717 g, 85 %) as a yellow solid after filtration and concentration which
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was used with no further purification. M.p. = 74-75 °C; H NMR (CDCl3, 300 MHz) δ 12.19 (1H, s),
7.51 – 7.41 (2H, m), 7.33 (1H, dd, J = 8.0 and 1.8 Hz), 7.28 (1H, dd, J = 7.5 and 1.8 Hz), 7.08 – 6.98
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(3H, m), 6.79 (1H, ddd, J = 8.1, 7.2 and 1.2 Hz), 3.76 (3H, s); 13C{H} NMR (CDCl3, 75 MHz) δ 202.1,
162.9, 156.6, 136.4, 133.8, 131.9, 128.8, 127.8, 120.5, 120.2, 118.7, 118.0, 111.5, 55.6; IR (solid) νmax
(cm-1) = 3026, 2968, 2939, 2835, 1601, 1483, 1463, 1447, 1333, 1306, 1279, 1244, 1146, 1117, 1101,
1020, 932, 824, 793, 748, 698, 640; ESI-MS TOF (m/z) calculated [M+H]+ for C14H13O3 229.0865,
found 229.0866.17
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General procedures for the synthesis of benzophenones 17-21. The relevant substituted benzene 22b-f
(1.1 eq) was added to a dry 2-necked flask before the flask was fitted with a rubber septum, stirrer bar
and attached to a nitrogen line. The flask was evacuated and charged with nitrogen three times before
dry THF was added to dilute the benzene. The solution was cooled to ˗78 °C and n-BuLi (1.1 eq) was
added dropwise and the reaction mixture stirred at ˗78°C for 30 mins. In a separate 2-neck flask, benzyl
2-(benzyloxy)benzoate (1 eq) was added, fitted with a stirrer bar and rubber septum and attached to a
nitrogen line. The second flask was evacuated and charged with nitrogen three times before the addition
of dry THF. Once the ester had completely dissolved, the solution was cooled to ˗78 °C with high
stirring. The lithiated solution from the first flask was added to the ester solution dropwise over several
mins. The mixture was left to react at ˗78 °C for 1-2 h under nitrogen before being quenched with
saturated NH4Cl and warmed to rt. The suspension was extracted with water and washed with EtOAc.
The organic layer was further washed with brine, dried over anhydrous Na2SO4 and concentrated in
vacuo. The resulting products 23b-f were purified by flash column chromatography with 10-20 %
EtOAc/Hexane as the eluent and characterised by NMR spectroscopy. As the next step 10% palladium
on activated carbon (10 mass %) was added to the freshly synthesized benzophenones 23b-f (1 eq) and
the contents carefully dissolved in MeOH. The resulting suspension was then exposed to a H2
atmosphere at ambient pressure, stirred at room temperature for 12 h. The suspension was filtered
through a Celite/flash silica plug to remove the palladium catalyst, washed with EtOAc and
concentrated in vacuo. If all the palladium was successfully removed the product was used with no
further purification, if not the product was purified by silica column chromatography (20%
EtOAc/Hexane) resulting in the synthesis of benzophenones 17-21.
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(2,3-Dimethoxyphenyl)(2-hydroxyphenyl)methanone (17).19 Veratrole 22b (2.39 g, 17.30 mmol, 1.1
1
2
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eq) was treated with n-BuLi (13.5 ml, 1.28M, 17.30 mmol, 1.1 eq) at ˗78 °C in dry THF. This solution
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was added to benzyl 2-(benzyloxy)benzoate (5.00 g, 15.73 mmol) and the general procedure followed.
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After
purification
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flash
column
chromatography,
(2-(benzyloxy)phenyl)(2,3-
dimethoxyphenyl)methanone 23b was collected as a liquid (2.35 g, 43 %). 1H NMR (500 MHz, CDCl3):
δH = 7.62 (1H, dd, J = 7.6 and 1.8 Hz), 7.43 (1H, ddd, J = 8.3, 7.4 and 1.8 Hz), 7.19 (3H, dd, J = 5.1
and 2.0 Hz), 7.07 (1H, dd, J = 7.7 and 1.7 Hz), 7.03 (2H, t, J = 7.8 Hz), 6.96 (4H, ddd, J = 7.9, 5.2 and
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1.2 Hz), 4.93 (2H, s), 3.80 (3H, s), 3.52 (3H, s); C{H} NMR (125 MHz, CDCl3): δC = 195.7, 157.4,
152.7, 148.0, 136.3, 135.8, 132.9, 130.5, 130.3, 128.2, 127.5, 126.8, 123.6, 121.1, 120.7, 115.1, 112.5,
70.1, 61.3, 56.0; IR νmax.(cm-1) = 2943, 2889, 2835, 1647, 1593, 1566, 1485, 1458, 1431, 1377, 1296,
1269, 1242, 1161, 1107, 1080, 1053, 1026, 999, 972, 837, 756, 702, 621; ESI-MS TOF (m/z)
calculated [M+H]+ for C22H21O4 349.1440, found 349.1442. Methanol was used to dissolve 23b (2.35 g,
6.76 mmol) and 5 % Pd/C (0.24 g, 10 mass %) added. After stirring under a H2 atmosphere and
purification according to the general procedure, benzophenone 17 was collected as a white solid (1.16 g,
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66 %). M.p. = 75-77 °C. H NMR (CDCl3, 300 MHz) δ 12.16 (1H, s), 7.45 (1H, ddd, J = 8.7, 7.2 and
1.8 Hz), 7.35 (1H, dd, J = 8.0 and 1.7 Hz), 7.11 (1H, d, J = 7.5 Hz), 7.03 (2H, m), 6.85 (1H, dd, J = 7.4
and 1.7 Hz), 6.79 (1H, ddd, J = 8.2, 7.2 and 1.2 Hz), 3.90 (3H, s), 3.77 (3H, s); 13C{H} NMR (CDCl3,
75 MHz) δ 201.8, 162.9, 152.8, 146.2, 136.7, 133.9, 133.0, 124.1, 120.1, 119.8, 118.8, 118.0, 114.4,
61.7, 55.9; IR (solid) νmax (cm-1) = 3678, 2984, 2868, 2839, 2810, 1624, 1595, 1566, 1479, 1450, 1422,
1335, 1306, 1248, 1161, 1074, 1045, 1016, 959, 843, 814, 785, 756, 698, 669, 611; ESI-MS TOF (m/z)
calculated [M+H]+ for C15H15O4 259.0970, found 259.0972.
(2-Hydroxyphenyl)(2,4,6-trimethoxyphenyl)methanone
(18).20
Combining
2-bromo-1,3,5-
trimethoxybenzene 22c (4.27 g, 17.28 mmol, 1.1 eq), n-BuLi (13.5 ml, 17.28 mmol, 1.28 M, 1.1 eq) and
benzyl 2-(benzyloxy)benzoate (5.00 g, 15.71 mmol, 1 eq) according to the general procedure resulted in
the formation of a yellow oil that was determined to be (2-(benzyloxy)phenyl)(2,4,6-
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trimethoxyphenyl)methanone 23c (2.65 g, 45 %). H NMR (300 MHz, CDCl3): δH = 7.72 (1H, dd, J =
7.7 and 1.9 Hz), 7.35 (1H, ddd, J = 8.3, 7.3 and 1.9 Hz), 7.24 (3H, dd, J = 5.0 and 1.9 Hz), 7.12 (2H, dd,
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J = 6.7 and 2.9 Hz), 7.00 – 6.88 (2H, m), 5.96 (2H, s), 4.89 (2H, s), 3.72 (3H, s), 3.52 (6H, s); 13C{H}
NMR (75 MHz, CDCl3): δC = 193.3, 162.1, 158.8, 157.9, 136.5, 133.1, 131.3, 130.3, 128.1, 127.5,
127.3, 120.5, 114.8, 113.0, 90.8, 70.3, 55.8, 55.2; IR νmax (cm-1) = 3001, 2978, 2931, 2862, 2839, 1659,
1485, 1458, 1431, 1377, 1296, 1242, 1161, 1107, 1026, 999, 918, 891, 849, 802, 779, 756, 733, 687,
640, 617; ESI-MS TOF (m/z) calculated [M+H]+ for C23H23O5 379.1545, found 379.1546. The benzyl
group of 22c (2.342 g, 6.19 mmol) was removed using 5 % Pd/C (0.234 g, 10 mass %) under a H2
atmosphere as described in the general procedure. After filtration the product was recrystallized from
isopropyl alcohol resulting in the collection of light yellow crystals of 18 (1.322 g, 74 %). M.p. = 144-
146 °C. 1H NMR (CDCl3, 300 MHz) δ 12.23 (1H, s), 7.44 (1H, ddd, J = 8.6, 7.1 and 1.8 Hz), 7.32 (1H,
dd, J = 8.0 and 1.8), 7.00 (1H, dd, J = 8.4 and 1.2 Hz), 6.78 (1H, ddd, J = 8.2, 7.2 and 1.1 Hz), 6.17
(2H, s), 3.86 (3H, s), 3.71 (6H, s); 13C{H} NMR (CDCl3, 75 MHz) δ 201.1, 162.8, 162.6, 158.4, 136.2,
133.2, 121.4, 118.7, 117.8, 109.7, 90.7, 55.9, 55.5; IR (solid) νmax (cm-1) = 3686, 2970, 2943, 2930,
2862, 2862, 2849, 1607, 1580, 1485, 1404, 1337, 1296, 1242, 1229, 1202, 1188, 1148, 1121, 1053,
1026, 1013, 959, 932, 824, 797, 756, 716; ESI-MS TOF (m/z) calculated [M+H]+ for
C16H17O5 289.1076, found 289.1082.20
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(2,4-Dimethoxyphenyl)(2-hydroxyphenyl)methanone
(19).21
Combining
1-bromo-2,4-
dimethoxybenzene 22d (3.77 g, 17.30 mmol, 1.1 eq), n-BuLi (13.5 ml, 17.30 mmol, 1.28 M, 1.1 eq) and
benzyl 2-(benzyloxy)benzoate (5.00 g, 15.73 mmol, 1 eq) according to the general procedure resulted in
the formation of
a
yellow oil that was determined to be (2-(benzyloxy)phenyl)(2,4-
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dimethoxyphenyl)methanone 23d (5.03 g, 92 %). H NMR (300 MHz, CDCl3): δH = 7.58 (1H, dd, J =
8.7 and 1.3 Hz), 7.50 (1H, dd, J = 7.5 and 1.8 Hz), 7.42 – 7.34 (1H, m), 7.24 – 7.17 (3H, m), 7.06 – 6.96
(3H, m), 6.94 (1H, dd, J = 8.4 and 1.0 Hz), 6.48 (1H, dd, J = 8.6 and 2.3 Hz), 6.33 (1H, d, J = 2.2 Hz),
4.95 (2H, s), 3.81 (3H, s), 3.57 (3H, s); 13C{H} NMR (75 MHz, CDCl3): δC = 194.1, 164.1, 160.7,
156.6, 136.6, 133.0, 132.0, 131.7, 129.8, 128.1, 127.4, 126.6, 123.2, 120.8, 112.3, 104.7, 98.6, 70.1,
55.6, 55.4; IR νmax.(cm-1) = 3013, 2947, 2843, 1624, 1601, 1504, 1483, 1433, 1333, 1306, 1285, 1242,
1209, 1150, 1144, 1030, 945, 826, 758; ESI-MS TOF (m/z) calculated [M+H]+ for C22H21O4 349.1440,
found 349.1438. Ketone 23d (4.86 g, 13.99 mmol) and 5 % Pd/C (0.486 g, 10 mass %) were combined
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according to the general hydrogenation procedure. A yellow oil was collected after purification and
confirmed to be 19 (2.58 g, 71 %). 1H NMR (CDCl3, 300 MHz) δ 12.24 (1H, s), 7.42 (2H, m, J = 8.3,
7.9 and 1.7 Hz), 7.27 (1H, d, J = 8.1 Hz), 7.00 (1H, dd, J = 8.4 and 1.2 Hz), 6.79 (1H, ddd, J = 8.1, 7.2
and 1.1 Hz), 6.59 – 6.46 (2H, m), 3.86 (3H, s), 3.74 (3H, s); 13C{H} NMR (CDCl3, 125 MHz) δ 201.2,
163.2, 162.8, 158.6, 136.1, 133.8, 131.0, 120.7, 120.5, 118.5, 118.0, 104.6, 98.9, 55.6, 55.5; IR νmax
(cm-1) = 2936, 2839, 1605, 1508, 1470, 1412, 1335, 1315, 1277, 1238, 1200, 1161, 1123, 1026, 949,
949, 910, 949, 910, 833, 795, 756, 737, 698, 640, 621; ESI-MS TOF (m/z) calcd for
C15H15O4 259.0970, found 259.0974.
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(2,6-Dimethoxyphenyl)(2-hydroxyphenyl)methanone (20).19 1,3-dimethoxybenzene 22e (2.39 g,
17.30 mmol, 1.1 eq) and n-BuLi (13.5 ml, 1.28 M, 17.30 mmol, 1.1 eq) at ˗78 °C in dry THF. This
solution was added to benzyl 2-(benzyloxy)benzoate (5.00 g, 15.73 mmol, 1 eq) also at ˗78 °C and the
reaction mixture stirred for 2 h. The reaction was quenched and purified as outlined in the general
procedure and (2-(benzyloxy)phenyl)(2,6-dimethoxyphenyl)methanone 23e was collected as a peach
solid (4.41 g, 81 %). M.p. = 85-87 °C. 1H NMR (300 MHz, CDCl3): δH = 7.77 (1H, dd, J = 7.7 and 1.8
Hz), 7.37 (1H, ddd, J = 8.4, 7.3 and 1.9 Hz), 7.30 (2H, d, J = 4.6 Hz), 7.24 (2H, dd, J = 5.2 and 1.8 Hz),
7.15 (1H, d, J = 8.5 Hz), 7.13 – 7.09 (1H, m), 6.96 (1H, dd, J = 7.6 and 1.0 Hz), 6.94 – 6.87 (1H, m),
6.42 (2H, d, J = 8.4 Hz), 4.90 (2H, s), 3.55 (6H, s); 13C{H} NMR (75 MHz, CDCl3): δC = 194.1, 158.3,
157.3, 136.4, 133.6, 131.7, 130.1, 128.2, 127.4, 127.2, 126.9, 120.5, 113.2, 104.2, 70.3, 55.8; IR
νmax.(cm-1) = 2943, 2889, 2835, 2376, 1674, 1593, 1485, 1458, 1431, 1296, 1269, 1242, 1161, 1107,
1026, 999, 945, 918, 864, 783, 756, 729, 702, 621; ESI-MS TOF (m/z) calculated [M+H]+ for
C22H21O4 349.1440, found 349.1440. Following the general procedure, benzophenone 23e (4.08 g,
11.71 mmol) H2 gas and 5 % Pd/C (0.41 g, 10 mass %) was used to remove the benzyl group resulting
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in the collection of a yellow solid that was confirmed to be 20 (1.82 g, 60 %). M.p. = 104-107°C. H
NMR (CDCl3, 300 MHz) δ 12.15 (1H, s), 7.44 (1H, ddd, J = 8.7, 7.2 and 1.8 Hz), 7.36 (1H, t, J = 8.4
Hz), 7.28 (1H, dd, J = 7.9 and 1.7 Hz), 7.01 (1H, dd, J = 8.4 and 1.1 Hz), 6.77 (1H, ddd, J = 8.1, 7.2
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and 1.1 Hz), 6.62 (2H, d, J = 8.4 Hz), 3.71 (6H, s); C{H} NMR (CDCl3, 75 MHz) δ 201.3, 162.5,
157.3, 136.4, 133.0, 131.3, 121.0, 118.9, 117.9, 116.5, 104.0, 55.9; IR (solid) νmax (cm-1) = 3699, 2978,
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2936, 2851, 1620, 1578, 1472, 1450, 1366, 1344, 1302, 1281, 1238, 1132, 1111, 1069, 1026, 941, 835,
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793, 772, 750, 729, 623; ESI-MS TOF (m/z) calcd for C15H15O4 259.0970, found 259.0971.
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(3,4-Dimethoxyphenyl)(2-hydroxyphenyl)methanone
(21).22
Combining
4-bromo-1,2-
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dimethoxybenzene 22f (3.78 g, 17.30 mmol, 1.1 eq), n-BuLi (13.5 ml, 17.30 ml, 1.1 eq) and benzyl 2-
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(benzyloxy)benzoate (5.00 g, 15.73 mmol, 1 eq) according to the general procedure resulted in the
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formation of
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yellow oil that was determined to be (2-(benzyloxy)phenyl)(3,4-
dimethoxyphenyl)methanone 23f (2.41 g, 44 %). 1H NMR (300 MHz, CDCl3): δH = 7.58 (1H, d, J = 8.6
Hz), 7.50 (1H, dd, J = 7.5 and 1.8 Hz), 7.43 – 7.32 (1H, m), 7.23 – 7.16 (3H, m), 7.05 – 6.93 (4H, m),
6.48 (1H, dd, J = 8.6 and 2.3 Hz), 6.33 (1H, d, J = 2.3 Hz), 4.95 (2H, s), 3.81 (3H, s), 3.57 (3H, s);
13C{H} NMR (125 MHz, CDCl3): δC = 194.1, 164.0, 160.7, 156.6, 136.6, 133.0, 132.0, 131.7, 129.8,
128.1, 127.4, 126.6, 123.2, 120.8, 112.3, 104.7, 98.5, 70.1, 55.6, 55.4; IR νmax.(cm-1) = 3024, 2943,
2862, 2376, 1647, 1593, 1521, 1485, 1458, 1431, 1296, 1269, 1107, 1053, 1026, 918, 729, 702; ESI-
MS TOF (m/z) calculated [M+H]+ for C22H21O4 349.1440, found 349.1441. Benzyl protected
benzophenone 23f (2.21 g, 6.34 mmol) was reduced using 5 % Pd/C (0.221 g, 10 mass %) under a H2
atmosphere. After purification by flash column chromatography, 21 was collected as a yellow solid
(1.01 g, 62 %). M.p. = 86-89 °C, 76-78 °C.23 1H NMR (CDCl3, 300 MHz) δ 11.97 – 11.82 (1H, s), 7.70
– 7.64 (1 H, m), 7.50 (1H, ddd, J= 8.6, 7.1 and 1.6 Hz), 7.36 – 7.30 (2H, m), 7.10 – 7.05 (1H, m), 6.94
(1H, d, J = 7.9 Hz), 6.92 – 6.85 (1H, m), 3.97 (3H, s), 3.94 (3H, s); 13C{H} NMR (CDCl3, 75 MHz) δ
199.9, 162.9, 152.7, 149.1, 135.8, 133.3, 130.5, 124.3, 119.5, 118.5, 118.4, 112.2, 110.1, 56.1, 56.1; IR
(solid) νmax (cm-1) 3424, 3007, 2972, 2936, 2833, 1618, 1584, 1514, 1479, 1462, 1447, 1410, 1358,
1323, 1306, 1254, 1219, 1167, 1132, 1115, 1063, 1028, 976, 889, 854, 820, 802, 768, 750, 698, 646,
611; ESI-MS TOF (m/z) calculated [M+H]+ for C15H15O4 259.0970, found 259.0974.
4-Methoxy-9H-xanthen-9-one (24).19 Benzophenone 17 (0.117 g, 0.453 mmol) was dissolved in
MeCN (20 ml), distilled H2O (10 ml) and CHCl3 (5 ml) under N2. CAS۰2H2O (1.146 g, 1.812 mmol,
4.00 eq) was added and the reaction mixture stirred rapidly for 18 h. Only a single spot was visualized
on the TLC plate. This product was characterised by NMR spectroscopy and determined to be 24 (0.061
g, 60 %). M.p. = 178 °C, 175-176 °C.19 1H NMR (CDCl3, 300 MHz) δ 8.35 (1H, ddd, J = 7.9, 1.7 and
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0.5 Hz), 7.92 (1H, dd, J = 7.8 and 1.8 Hz), 7.74 (1H, ddd, J = 8.7, 7.0 and 1.8 Hz), 7.62 (1H, ddd, J =
8.5, 1.1 and 0.5 Hz), 7.40 (1H, ddd, J = 8.1, 7.1 and 1.2 Hz), 7.32 (2H, m), 4.04 (3H, s); 13C{H} NMR
(CDCl3, 75 MHz) δ 177.2, 156.0, 148.7, 146.6, 134.8, 126.7, 124.1, 123.4, 122.8, 121.7, 118.3, 117.7,
115.4, 56.5; IR (solid) νmax (cm-1) 2993, 2955, 2916, 2858, 2839, 1663, 1605, 1566, 1489, 1470, 1450,
1354, 1335, 1277, 1258, 1238, 1200, 1142, 1065, 1026, 968, 891, 853, 814, 756, 718, 679, 621; ESI-
MS TOF (m/z) calculated [M+H]+ for C14H11O3 227.0708, found 227.0704.
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2',6'-Dimethoxy-3H-spiro[benzofuran-2,1'-cyclohexa[2,5]diene]-3,4'-dione (25). To a solution of 18
(0.300 g, 1.041 mmol) in MeCN (40 ml), H2O (20 ml) and CHCl3 (10 ml), CAS۰2H2O (2.634 g, 4.164
mmol, 4.00 eq) was added and stirred for 18 h. After purification by flash column chromatography,
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white crystals were collected and identified as 25 (0.166 g, 59 %). M.p. = 194-196 °C. H NMR
(CDCl3, 300 MHz) δ 7.75 – 7.63 (2H, m), 7.26 – 7.20 (1H, m), 7.17 (1H, ddd, J = 7.9, 7.2 and 0.8 Hz),
13
5.64 (2H, d, J = 1.0 Hz), 3.64 (6H, s); C{H} NMR (CDCl3, 75 MHz) δ 194.4, 186.8, 173.8, 164.8,
138.6, 125.3, 122.7, 120.1, 113.5, 103.5, 84.3, 56.5; IR (solid) νmax (cm-1) 2972, 2938, 2920, 2868,
2816, 1722, 1670, 1636, 1601, 1462, 1358, 1323, 1306, 1236, 1219, 1184, 1150, 1097, 1063, 993, 924,
889, 854, 768, 716, 629; ESI-MS TOF (m/z) calculated [M+H]+ for C15H13O5 273.0763, found
273.0764.
(4,4'-Dihydroxy-[1,1'-biphenyl]-3,3'-diyl)bis((2,4-dimethoxyphenyl)methanone)
(26).
Benzophenone 19 (0.521 g, 2.017 mmol) was dissolved in MeCN (40 ml), H2O (20 ml) and CHCl3 (5
ml) and CAS۰2H2O (2.552 g, 4.035 mmol, 2.00 eq) was added. After stirring overnight under a N2
atmosphere and purification by flash column chromatography, 26 (0.082 g, 24 %) was isolated as a
white solid. M.p. = 171-175 °C. 1H NMR (CDCl3, 300 MHz) δ 12.15 (1H, s), 7.51 (1H, dd, J = 8.6 and
2.4 Hz), 7.42 (1H, d, J = 2.4 Hz), 7.28 (1H, d, J = 8.4 Hz), 7.04 (1H, d, J = 8.6 Hz), 6.55 (1H, dd, J =
8.4 and 2.3 Hz), 6.51 (1H, d, J = 2.2 Hz), 3.91 (3H, s), 3.61 (3H, s); 13C{H} NMR (CDCl3, 75 MHz) δ
201.1, 163.3, 162.0, 158.5, 134.4, 131.3, 131.1, 130.8, 120.7, 120.5, 118.5, 104.7, 99.1, 55.6, 55.5; IR
(solid) νmax (cm-1) 2972, 2938, 2851, 1601, 1584, 1514, 1462, 1410, 1323, 1288, 1236, 1202, 1167,
1132, 1115, 1028, 976, 941, 820, 785, 768, 611; ESI-MS TOF (m/z) calculated [M+H]+ for
C30H27O8 515.1706, found 515.1702.
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(4,4'-Dihydroxy-[1,1'-biphenyl]-3,3'-diyl)bis((2,6-dimethoxyphenyl)methanone) (27). A solution of
MeCN (30 ml), H2O (15 ml) and CHCl3 (7.5 ml) was used to dissolve benzophenone 20 (0.291 g, 1.127
mmol) and CAS۰2H2O (2.138 g, 3.380 mmol, 3.00 eq) was added with high stirring for 18 h. Following
purification by flash column chromatography 27 was collected as a yellow oil (0.052 g, 18 %). 1H NMR
(CDCl3, 300 MHz) δ 12.13 (1H, s), 7.50 (1H, dd, J = 8.7 and 2.4 Hz), 7.42 – 7.33 (1H, m), 7.22 (1H, d,
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J = 2.4 Hz), 7.04 (1H, d, J = 8.6 Hz), 6.59 (2H, d, J = 8.4), 3.63 (6H, s); C{H} NMR (CDCl3, 75
MHz) δ 201.1, 161.8, 157.3, 134.9, 131.3, 131.2, 130.5, 120.9, 118.4, 116.3, 104.1, 55.9; IR νmax (cm-1)
3009, 2978, 2947, 2839, 1636, 1589, 1466, 1435, 1327, 1281, 1250, 1219, 1157, 1111, 1049, 1034, 941,
833, 787, 756, 725, 632; ESI-MS TOF (m/z) calculated [M+H]+ for C30H27O8 515.1706, found
515.1707.
(4,4'-Dihydroxy-[1,1'-biphenyl]-3,3'-diyl)bis((3,4-dimethoxyphenyl)methanone)
(28).
Benzophenone 21 (0.409 g, 1.584 mmol) was dissolved in MeCN (20 ml), H2O (10 ml) and CHCl3 (5
ml). To this rapidly stirring solution CAS۰2H2O (2.00 g, 3.167 mmol, 2.00 eq) was added under a N2
atmosphere and stirred overnight. Following purification by flash column chromatography, a yellow
solid was collected that was determined to be 28 (0.062 g, 15 %). M.p. = 148-150 °C. 1H NMR (CDCl3,
300 MHz) δ 11.78 (1H, s), 7.78 (1H, d, J = 2.4 Hz), 7.64 (1H, dd, J = 8.6 and 2.4 Hz), 7.35 (1H, d, J =
2.0 Hz), 7.32 (1H, dd, J = 8.2 and 2.0 Hz), 7.13 (1H, d, J = 8.6 Hz), 6.86 (1H, d, J = 8.2 Hz), 3.96 (3H,
s), 3.90 (3H, s); 13C{H} NMR (CDCl3, 75 MHz) δ 199.5, 162.1, 153.0, 149.2, 133.9, 130.9, 130.6,
130.2, 124.5, 119.6, 119.0, 112.1, 109.9, 56.1, 56.0; IR (solid) νmax (cm-1) 3013, 2974, 2974, 2936,
2858, 2839, 1624, 1566, 1508, 1470, 1412, 1335, 1258, 1238, 1200, 1180, 1142, 1065, 1026, 872, 814,
795, 756, 698, 660, 621; ESI-MS TOF (m/z) calculated [M+H]+ C30H27O8 515.1706, found 515.1704.
General experimental procedure for the conversion of diones to xanthones (34a-d). In a 25 ml round
bottomed flask, dione, 7, 8, 11 and 12 (1 eq) was dissolved in freshly distilled THF (5 ml). To this 5 ml
of water was added and 3 equivalents of sodium dithionite was added to the solution while being stirred
at a high speed. Just after the addition of the sodium dithionite a colour change of the mixture was noted
and the solution was stirred for a further 15 mins. The reaction was monitored by TLC and when no
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further starting material was observed the mixture was transferred to a separation funnel and diluted
with 15 ml water and 15 ml diethyl ether. The water layer was removed and the organic layer washed
with a further 15 ml of water. Concentrated aq. NaOH (15 ml) was added to the organic layer, the
separation funnel stoppered and shaken vigorously. A notable change in colour was observed during
shaking. The aqueous layer (now highly coloured) was collected. Further addition of conc. NaOH along
with vigorous shaking was repeated until no further colour change was observed in the aqueous layer.
The basic aqueous layers that were collected, combined and neutralized by portionwise addition of solid
ammonium chloride until a solid precipitated out of solution, the solid collected by filtration and dried
in a desiccator overnight. The solids were characterised by NMR, infrared and mass spectroscopy.
2-Hydroxy-9H-xanthen-9-one (34a).23 Dione 7 (0.100 g, 0.413 mmol) was reduced to 34a with
sodium dithionite (0.216 g, 1.239 mmol, 3.00 eq). The product 34a was collected as a cream coloured
powder (0.079 g, 90 %). M.p. = >310 °C. 1H NMR (CD3OD, 300 MHz) δ 8.25 (1H, dd, J = 8.1 and 1.7
Hz), 7.81 (1H, ddd, J = 8.7, 7.1 and 1.7 Hz), 7.60 – 7.54 (2 H, m), 7.49 (1H, d, J = 9.1 Hz), 7.43 (1H,
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ddd, J = 8.1, 7.0 and 1.1 Hz), 7.33 (1H, dd, J = 9.1 and 3.0 Hz); C{H} NMR (CD3OD, 75 MHz) δ
179.0, 157.7, 155.4, 151.6, 136.3, 127.2, 125.9, 125.0, 123.2, 122.0, 120.5, 119.2, 109.8; IR (solid)
νmax(cm-1) 3302, 3069, 2947, 2872, 1651, 1614, 1597, 1460, 1342, 1302, 1223, 1146, 1190, 1130, 871,
816, 787, 748, 711, 619; ESI-MS TOF (m/z) calculated [M-H]- for C13H7O3 211.0401, found
211.0399.
2-Chloro-7-hydroxy-9H-xanthen-9-one (34b).24 The reduction of dione 11 (0.257 g, 0.929 mmol)
was performed using sodium dithionite (0.485 g, 2.786 mmol, 3.00 eq) resulting in the formation of a
beige powder 34b (0.171 g, 75 %) after the work up given in the general procedure. M.p. = 250 °C, lit
221-222 °C.22 1H NMR (d-DMSO, 500 MHz) δ 7.85 (1H, d, J = 2.6 Hz), 7.45 (1H, dd, J = 9.0 and 2.7
Hz), 7.26 (1H, d, J = 8.9 Hz), 7.21 (1H, d, J = 3.0 Hz), 7.17 (1H, d, J = 9.1 Hz), 7.01 (1H, dd, J = 9.0
13
and 3.0 Hz); C{H} NMR (d-DMSO, 126 MHz) δ 180.3, 158.6, 158.4, 154.0, 138.7, 133.0, 128.83,
128.76, 125.5, 124.0, 123.1, 112.4; IR (solid) νmax (cm-1) 3312, 2984, 2959, 2878, 1651, 1616, 1476,
1375, 1285, 12238, 1150, 1059, 1034, 1030, 891, 889, 820, 795, 733, 689, 629; ESI-MS TOF (m/z)
calculated [M+H]+ for C13H8O3Cl 247.0162, found 247.0157.
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5-Hydroxy-7H-benzo[c]xanthen-7-one (34c). In the presence of sodium dithionite (0.179 g, 1.026
mmol, 3.00 eq), dione 8 (0.100 g, 0.342 mmol) was reduced to 34c following the general procedure
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resulting in the formation of a yellow solid (0.057 g, 64 %). M.p. = decomposed at 260 °C. H NMR
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7
8
9
(CDCl3, 300 MHz) δ 8.64 (1H, dt, J = 6.8 and 3.4 Hz), 8.34 (1H, dt, J = 7.0 and 3.5 Hz), 8.27 – 8.19
(1H, m), 7.94 – 7.84 (2H, m), 7.80 (2H, dt, J = 6.4 and 3.5 Hz), 7.50 (1H, ddd, J = 8.1, 5.8 and 2.3 Hz),
7.42 (1H, s); 13C{H} NMR (CDCl3, 75 MHz) δ 175.5, 155.1, 151.4, 146.1, 134.4, 129.4, 128.7, 127.4,
125.6, 124.5, 124.2, 123.0, 122.4, 121.1, 118.3, 117.9, 99.1; IR (solid) νmax(cm-1) 3329, 3074, 1624,
1607, 1581, 1470, 1420, 1286, 1265, 1234, 1130, 1076, 1022, 889, 858, 842, 771, 745, 698, 661,
635;ESI-MS TOF (m/z) calculated [M+H]+ for C17H11O3 263.0708, found 263.0716.
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9-Chloro-5-hydroxy-7H-benzo[c]xanthen-7-one (34d). Following the general procedure, dione 12
(0.146 g, 0.447 mmol) was reduced by sodium dithionite (0.233 g, 1.341 mmol, 3.00 eq). The product
was collected as a yellow solid and determined to be 34d (0.090 g, 68 %). M.p. = decomposed >270 °C.
1H NMR (d-DMSO, 500 MHz) δ 8.63 – 8.56 (1H, m), 8.29 – 8.24 (1H, m), 8.08 (1H, d, J = 1.5 Hz),
7.88 (2H, d, J = 1.6 Hz), 7.83 – 7.77 (2H, m), 7.38 (1H, s); 13C{H} NMR (d-DMSO, 126 MHz) δ
175.0, 154.2, 150.6, 147.4, 134.9, 129.9, 129.2, 128.3, 124.9, 123.2, 123.15, 123.09, 122.6, 121.4,
117.8, 99.7; IR (solid) νmax(cm-1) 3323, 2981, 2924, 2868, 1626, 1601, 1685, 1452, 1402, 1267, 1117,
1057, 1034, 1016, 893, 585, 812, 766, 710, 665, 615; ESI-MS TOF (m/z) calculated [M+H]+ for
C17H10O3Cl 297.0318, found 297.0312.
1
SUPPORTING INFORMATION PARAGRAPH Supporting Information is available containing H
and 13C NMR spectra and crystallographic information file (CIF) for compound 26.
ACKNOWLEDGMENT This work was supported by by SABINA (Southern African Biochemistry and
Informatics for Natural Products Network). the National Research Foundation, Pretoria, South Africa,
the University of the Witwatersrand (Science Faculty Research Council). Dr Stuart Millar is thanked for
the PXRD work. Professor Roger Hunter (University of Cape Town), Professor Hans-Gunther Schmalz
(University of Cologne) and a reviewer of this manuscript are thanked for useful discussions.
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