chapter 6: uncatalyzed synthesis of hexahydroxanthenes in aqueous
TRANSCRIPT
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
209
Introduction:
Xanthenes are frequently occurring motifs in a number of natural products1 and
have been used as versatile synthons due to the inherent reactivity of the inbuilt pyran
ring2. Most of the natural schweinfurthins3 (diversonol and blennolide C, Fig. 1) are
potent and selective inhibitors of cell growths measured by the National Cancer
Institute’s 60-cell line screen4. Xanthenes are known for their utility as leuco-dyes5, pH-
sensitive fluorescent materials for the visualization of biomolecules6 and in laser
technologies7 due to their useful spectroscopic properties.
OH OHO
OH
O
OH O
O
OH
OH
OH
OH OHO
OH
O
O
OOH
MeO2C
blennolide Cdiversonol
MeO2C
secalonic acids
Fig. 1
Xanthene derivatives have also applications in synthesis of aromatic polyamides,8
which are characterized as high thermally stable polymers with a favorable balance of
physical and chemical properties9. But these polymers are usually difficult to process due
to their high softening temperatures and their insoluble nature in most organic solvents.
Current or prior numerous attempts have been made to improve their process ability by
the introduction of flexible linkage10, molecular asymmetry11, or substituted group12 into
the backbone of polyamides. Introducing cardo groups such as tert-
butylcyclohexylidene13 is a successful approach for improving the processability of
aromatic polyamides without an extreme loss of their outstanding properties.
Furthermore, it is well known that the incorporation of trifluoromethyl substituents into
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
210
polyamide backbones resulted in great benefits for improving polymer solubility and
photoelectric properties14. Figure 2 represent aromatic polyamide with trifluoromethyl
and xanthene pendent groups, based on a novel diamine monomer, 9,9-bis[4-(2-
trifluoromethyl-4-aminophenoxy)phenyl]xanthene (BTFAPX) [Fig. 3].
Fig. 2
O
O
F3C
NH2
O
H2N CF3
Fig. 3
Fluorescent organic dyes are widely used as non-radioactive labels and as a key
component of optical bio-probes for various biosensing and imaging applications.15
Xanthene-based dyes such as rhodamines16 and fluoresceins17 are among the most
commonly used class of fluorescent detection reagents.
O OHO O NR2R2N X+ _
OX X
O
O
Fluorone 1 Rosamine 2X= OH, Fluorescein 3
X= NR2, Rhodamine 4
Fig. 4
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
211
Xanthene dyes are also efficient as photo initiators of the free radical
polymerization in aqueous medium18 [Fig. 5].
O OOH
COOH
Monomer
PHOTOINITIATION EFFICIENCY
PHOTOCHEMICAL BEHAVIOR
hv+
Fig.5
Xanthenes and xanthene derivatives exhibit anti-cancer19, anti-oxidant20,
anti-inflammatory and potential analgesic activities21. Xanthenes are rare in natural
plants; most of them are synthesized or arise as a microbial metabolite. To date, xanthene
has only been isolated from two plant families, Fabaceae and Compositae22,23 [Pic. 1].
Recently, Huang et al.24 reported first example of a halogenated xanthene from a natural
plant [the aerial parts of Blumea riparia (Bl.) DC, a Chinese medicinal plant] with
hemostatic properties. Here, compound 1[Fig. 6] was tested for its in vitro cytotoxicity
against Bel-7404 liver cancer cells. At a concentration of compound 1 of 25 µg/L or 50
µg/L, the rate of inhibition of cell growth was 21.4 and 29.4 %, respectively.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
212
Fabaceae Compositae
Blumea riparia
Pic.1
Fig. 6
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
213
Methods for the synthesis of xanthene derivatives:
1) Benzoxanthene derivatives are important biologically active heterocycles,
synthesized by mixing β-naphthol, an aromatic or aliphatic aldehyde, and a
1,3-dicarbonyl substrate [Scheme 1]. Several groups reported their work with various
Lewis acid systems such as (a) solvent-free with indium(III) chloride or phosphorus
pentoxide as catalyst25; (b) tetrabutyl ammonium fluoride in water26; (c) para-toluene
sulfonic acid in ionic liquid [bmim]BF427; (d) solvent-free with iodine28; (e) sodium
hydrogenosulfate on silica gel in dichloromethane29.
OH
R' H
O
+
O
OR'
R2
R2
O N
N
R' O
Me
O
Me
O
OR2
R2
N
N
O
OO
Me
Me
Scheme 1
2) 14-Aryl-14-H-dibenzoxanthenes can be synthesized from aldehydes and β-naphthol
in 1:2 proportions in presence of Lewis or Bronsted acids such as H2SO430, Sulfamic acid
31 or p-TSA32 [Scheme 2].
Scheme 2
3) Synthesis of 1,8-dioxo-octahydroxanthene is generally achieved by the condensation
of 5,5-dimethyl-1,3-cyclohexanedione with aromatic aldehyde using Lewis acid catalysts
such as p-dodecylbenzenesulfonic acid33, diammonium hydrogen phosphate34, silica gel
supported ferric chloride35, Dowex-50W36, polyethylene glycol37 [Path I, Scheme 3].
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
214
However, when substituted salicyladehydes are used instead of regular aldehydes in
above reaction, led to 1-oxo-1,2,3,4,9,10-hexahydroxanthene derivatives38 [Path II,
Scheme 3].
Scheme 3
4) The synthesis of 9-aryl-6-hydroxy-3H-xanthen-3-one fluorophores was reported by
James P. Bacci39 using aryl aldehydes and fluororesorcinol which proceed through a
triarylmethane intermediate followed by oxidative cyclization with DDQ [Scheme 4].
Scheme 4
Brase et al. reported synthesis of tetrahydroxanthenones using Ball milling as a
mechanochemical technique from salicyclaldehyde and cyclohexenone proceed through
domino oxa-Michael aldol reaction40 [Scheme 5].
OH
O O
DABCO
ball millingO
O
+
Scheme 5
5) A three-component one-pot synthesis of new 2,4-diamino-5H-chromeno[2,3-b]
pyridine-3-carbonitriles derived from 2-amino-1,1,3-tricyanopropene, salicylaldehyde
and secondary cyclic amine was reported by Shaabani et al41 [Scheme 6]. The reaction
is conducted in ethanol medium at ambient temperature in good to excellent yields.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
215
Scheme 6
6) The chemical synthesis of xanthone C-glycosides has never been reported. Yu et al.
reported a synthetic approach to mangiferin, isomangiferin, and homomangiferin for first
time, employing the C-glycosylation of a xanthene derivative with
perbenzylglucopyranosyl trifluoroacetimidate as the key step42 [Scheme 7].
OH
OH
COOH
PO
O
OMeMsO
OP
5 steps
5 steps
O
OBn
BnO
BnOBnO
O
CF3
NPh
O OH
OH
OOH
R'
RO
R2
Mangiferin: R=R2=H; R1= β-Glc
Scheme 7
Mangiferin [1, Fig. 6] was first isolated in 1908 as a coloring matter from the
mango tree (Mangiferin indica L., Anacardisaceae)43a. Mangiferin occurs most
abundantly in the stem bark of mango43b; nevertheless, it has also been found in many
angiosperm plants and ferns43c. Isomangiferin [2, Fig.6] and homomangiferin [3, Fig.6],
the 4-C-glycoside regioisomer and 3-o-methyl derivative of mangiferin, respectively,
mainly coexist with mangiferin in the mango leaves and twigs43d-e. Mangiferin exhibits a
wide spectrum of pharmacological effects, including, among others, immunomodulatory,
anti-inflammatory, anti-tumor, anti-diabetic43f, lipolytic, anti-microbial, and anti-allergic
activities43g. Many of these effects could be attributed to its anti-oxidant property; in fact,
mangiferin is a “super anti-oxidant” which is more potent than vitamins C and E43h.
Interestingly, this C-glycoside could traverse the blood-brain barrier and, thus, has
potential to ameliorate the oxidative stress in neurodegenerative disorders43i.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
216
Mangiferin (1) R=H, Isomangiferin (2)
Homomangiferin (3) R=Me
Fig.6
7) An efficient iron-catalyzed, microwave-promoted cascade benzylation-cyclization of
phenols was reported by Li et al.44 They utilized benzyl acetates, benzyl bromides and
benzyl carbonates as benzylating reagents. The reactions proceed to afford both 9-aryl
and 9-alkyl xanthene derivatives in good to high yields using FeCl3 as the catalyst under
MW irradiation [Scheme 8]. 1
OO
Scheme 8
8) Sohár and co-workers carried out the Biginelli reaction of formylferrocene, thiourea
and a variety of 1,3-dioxo components and synthesized novel ferrocenyl-2-thioxo-
dihydropyrimidines and condensed heterocycles catalyzed by boric acid and ytterbium
triflate, respectively45 [Scheme 9]. The interpretation of reactions were supported by
B3LYP/6-31 G(d) modelling studies.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
217
Fe
OR
R
O H FcH
HO
O H Fc O
N
N
S
O FcH
H
H
N
N
O
S
H
HFcH
Fc =
R1
R2
R, R1 = Me, Ph, CH2-CO2-alkyl, R2 = Me, Ph, O-alkyl, NEt2
Scheme 9
9) A general and efficient one-pot cascade/tandem approach to synthesize
unsymmetrical 9-aryl/heteroaryl xanthenes has been reported by Singh et al. using 10
mol % of Sc(OTf)3 as a catalyst46 [Scheme 10]. They extend this strategy to synthesize
9-(thioaryl) xanthenes through tandem carbon–sulfur (C–S) and carbon–carbon (C–C)
bond formation. Novel C–C and C–S bond cleavage promoted by Sc(OTf)3 is also
discussed during mechanistic investigation.
a : indole (1 equi.), FeCl3, anhydrous DCM, rt
Scheme 10
10) 2,6,7-Trihydroxyxanthen-3-ones are prepared by a one-pot protocol using alkali
peroxosulfates in the key step [Scheme 12]. The product hydroxylated 9-substituted
xanthenones47 shows an important class of dyes.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
218
Scheme 11
11) Benzyne prepared from o-trimethylsilyphenyl triflate and CsF reacts with
salicylaldehyde yielded xanthenes and xanthones. When the reaction was carried out
under basic conditions, 9-hydroxyxanthenes (xanthols) 48 were obtained in good yields
[Scheme 12].
OH
CHO OTf
tTMSR
CsF
MeCN
RT
O
OHH
R
+
Scheme 12
12) The condensation of 2-hydroxynaphthalene-1,4-dione with isatin or aldehyde
yielded spiro[dibenzo[b,i]xanthene-13,3′-indoline]-pentaones and 5H-dibenzo[b,i]
xanthene-tetraones49 [Scheme 13].
Scheme 13
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
219
13) While the condensation of dimedone and isatin or acenaphthene in aqueous media
resulted into formation of spiro[indoline-3,9’-xanthene]trione derivatives and
spiro[acenaphthene-1,9’-xanthene]-1’,2,8’ (2’h, 5’h)-trione50 [Scheme 14].
Scheme 14
14) Wiemer et al.51 synthesized the cis-fused hexahydroxanthene system through a
cascade cyclization initiated by Lewis acid-mediated epoxide opening, obtained a single
diasteromeric product [Scheme 15].
OCH3
OTBS
OMOM
CH3
CH3
CH3
O
BF3.OEt2
OCH3
OTBSCH3 CH3
OH H
CH3
Scheme 15
15] An efficient method has been developed for the synthesis of hexahydroxanthene-
9-N-arylamine derivatives52 through a one-pot reaction of cyclohexanone and morpholine
with salicylaldehyde imines in the presence of indium (III) chloride as a catalyst.
1-(4-Morpholino)-cyclohexene enamine prepared in situ from cyclohexanone and
O O
N
H
O
O
OO
p-TSA
H2O
Reflux
O
OO
O
N
O
OO
R
OX
2
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
220
morpholine in presence of 20 mol % InCl3 in acetonitrile under reflux condition, and used
without further purification, for the cyclization reaction with salicylaldehyde Schiff's
bases [Scheme 16].
O
+
O
NH
InCl 3 CH 3CN,reflux
OH
NCH3
,
ON
O
NHCH3
Scheme 16
Catalysts used and choice of catalyst for 1-oxo-hexahydro xanthenes:
In contrast to the widely studied 1,8-dioxo-octahydroxanthene derivatives33-37,
relatively scanty literature is available describing the chemistry of
1-oxo-hexahydroxanthenes38. Synthetic routes to 1-oxo-hexahydroxanthenes generally
involve prolonged heating in acid-catalyzed reactions of salicylaldehyde with
1,3-diketone. The classical methods involve catalysts viz 2,4,6-trichloro-1,3,5-triazine
(TCT)38a, KF/Al2O338b, CeCl3.7H2O
38c and triethyl-benzylammoniumchloride (TEBA as a
cationic surfactant)38d. Therefore an environmentally benign protocol for synthesis of
1-oxo-hexahydro xanthenes is highly desirable. In view of this, we are working on the
synthesis of 1-oxo-hexahydroxanthenes using an eco-friendly synthetic strategy. Hence
we report our findings.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
221
Objectives:
Our aim for undertaking this work as outlined above was:
i) To develop a truly “Green Method” for synthesis of hexahydroxanthenes from
aldehyde and dimedone/cyclohexane-1,3-dione.
ii) To avoid necessary use of catalyst as well as of solvent.
Present Work:
Recently, our group has carried out synthesis of 1,8-dioxo-octahydroxanthenes
from aromatic aldehydes and 1,3-diketones (1:2) in aqueous medium using envirocat
EPZ-10 as an ecofriendly catalyst53. In this transformation, we allude that the acid is
essential for cyclodehydration of product 3 to form 4 [Scheme 17].
R
RO
O CHO
R'
O
O O
R
R
R
R
R'
OH
O O
R
R
R
R
O
R'
no catalyst
R= H, CH3
+2
3
4
1 2
H O2
H O2
EPZ-10
100 0C
70 0C
Scheme 17: EPZ-10 catalyzed synthesis of 1,8-dioxo-octahydroxanthenes in aqueous medium.
In continuation with our research devoted to 1,8-dioxo-octahydroxanthenes, we
then focused our attention towards the synthesis of hexahydroxanthenes [Scheme 18]. By
keeping these ideas in mind and paraphrasing the concept reported by Sheldon ‘‘the best
solvent is no solvent’’ 54 and by Maggi ‘‘the best catalyst is no catalyst’’ 55, we can state
that the truly green protocol is one which involves no catalyst and no solvent or use of
water as a universal solvent.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
222
To meet with our commitments, initially we have carried out reaction of
salicyaldehyde and dimedone (1:2) in water at room temperature. However, the reaction
took place 10 % only after 5h. Inspired by these results we applied reflux conditions for
the same reaction and as per our expectation the desired hexahydroxanthene was obtained
in good yields [Scheme 18].
Scheme 18: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
The IR spectrum (Fig.7) of 9-(2-Hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-
3,3-dimethyl-2,3,4,9-tetrahydro-xanthen-1-one obtained from salicyldehyde and
dimedone showed the expected bands at 3188, 2954, 1630, 1594, 1489, 1374, 1241,
1188, 755 cm-1. The 1H NMR spectrum (Fig. 8) of the same compound showed the four
singlets at δ 0.99 , 1.03, 1.08 and 1.12 for the twelve protons of four methyl groups of
dimedone moiety, the multiplets at δ 1.90-2.03 and 2.31-2.63 are due to eight methylene
protons of dimedone moiety, the singlet at 4.66 is due to benzylic methine proton, the
aromatic protons appeared as two multiplets at 6.98-7.04 and 7.13-7.19, the singlet at
10.50 indicated presence of –OH group. This spectroscopic data is in agreement with the
expected structure.
Mechanism
In this reaction water (ε =78.6) helps in the easy conversion of the keto form to
enol form of the compound (2) which is useful for Knoevenagel condensation followed
by subsequent Michael addition and dehydration affords product (3). A plausible
mechanism is depicted in scheme 19.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
223
R
RO
O
R
RO
O
OH
CHO
O
R
R
OH
O
OH
OH
RR
OR
RO
OH
OH R
R
O
R
R
O
O
RR
OOH
OH
OH
H2O
H2O-H2O-
1
2
Scheme 19: Plausible mechanism for the catalyst-free synthesis of 1-oxo-hexahydro xanthenes in aqueous medium.
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
224
Table1: Catalyst-free synthesis of 1-oxo-hexahydroxanthenes.
Entry
Product (3) Time (h)
Yield (%)
MP obs. (lit.)oC
a
O
OOHO
3.5
90
204(206)56
b
O
OOHO
Cl
5
88
235(238)56
c
O
OOHO
OMe
4.5
85
231(230)56
d
O
OOHO
Br
5
86
251(253)56
e
O
OOHO
HO
4
93
217(----)
f
O
OOHO
Cl
Cl
4.5
87
231(235)56
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
225
a Yields refer to pure isolated products. b.All products are racemic mixtures.
g
3.5
88
242(244)56
h
O
OOHO
Cl
Cl
4
85
252(254)56
i
5
87
243(245)56
j
O
OOHO
Br
Br
5
89
254(255)56
k
O
OOHO
HO
4.5
91
240(----)
l
4.5
84
215(216)56
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
226
A series of substituted salicylaldehydes were then condensed with dimedone in
water without any catalyst at 100oC. Both electron-rich as well as electron-deficient
salicylaldehydes reacted effectively with 1,3-dicarbonyl compounds in aqueous medium.
(Entries 3a-3f, Table 1)
The examination of IR spectrum (Fig. 9) of 7-Hydroxy-9-(2-hydroxy-4,4-dimethyl-
6-oxo-cyclohex-1-enyl)-3,3-dimethyl-2,3,4,9-tetrahydroxanthen-1-one obtained by
condensation of 5-hydroxysalicyldehyde with dimedone showed that the carbonyl
stretching frequency of the starting aldehyde disappeared from the given 1720 cm-1 and
appeared at 1589 cm-1 because of 1,4-addition and band at 2958 is due to –OH group. 1H
NMR spectrum (Fig. 10) of the same compound exhibited a set of three singlet at 0.88
for six protons of two methyl groups of dimedone and at 0.95, 1.01 for three protons of
remaining two methyl groups from dimedone moiety where as eight methylene protons of
the same moiety appeared as multiplet between 1.96-2.49, benzylic methine proton
appeared as a singlet at 4.95, aromatic protons appeared at 6.37 as doublet, 6.45 as doublet
of doublet and a doublet at 6.74. The enolic proton from dimedone moiety appeared as
singlet at 9.07 while the phenolic proton appeared at 10.29 as broad singlet. The CMR
spectrum (Fig. 11) exhibited signals at 26.64, 29.69, 32.01, 41.21, 50.90, 99.98, 110.38,
114.10, 114.37, 116.39, 116.78, 126.72, 143.12, 154.10, 165.40, 195.54, and 196.12. Mass
spectrum (Fig. 12) of the same compound is also in agreement with the expected structure
having m/z 382 (M+).
To check the generality of the present protocol we decided to replace 1,3-diketone
i.e dimedone by cyclohexane-1,3-dione and it is found that present protocol equally
efficient for dimedone as well as cyclohexane-1, 3-dione. (entries 3g-3l, Table 1)
The product obtained by condensation of 4-hydroxysalicyldehyde and
cyclohexane-1,3-dione showed the expected bands in its IR spectrum ( Fig. 13) at 1589
cm-1 due to α, β-unsaturated carbonyl group and at 2954 cm-1 due to hydroxyl group. The 1H NMR spectrum (Fig. 14) of the same compound showed a multiplet at 1.65-2.21 for
12 methylene protons from cyclohexane-1,3-dione, a benzylic methine proton appeared
as a singlet at 4.92 and aromatic protons appeared at 6.29, 6.39, 6.74 as doublet, doublet
of doublet and doublet, respectively. The protons of enolic and phenolic –OH appeared at
9.38, 10.35 as singlet and broad singlet, respectively which is in agreement of the
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
227
expected structure. The CMR spectrum (Fig. 15) of the same compound showed signals
at 20.75, 20.85, 25.21, 27.73, 37.13, 99.98, 102.19, 112.27,112.80, 116.45, 120.00,
129.26, 150.55, signals at 156.55 and 166.96 are due to β-carbon of α,β-unsaturated
carbonyl functionality while signal at 196.54 is due to carbonyl group. Mass spectrum
(Fig. 16) of the same compound also supports the expected structure by showing m/z
326(M+).
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
228
Conclusion:
We have developed practical and truly eco-friendly method for the efficient
synthesis of 1-oxo-hexahydroxanthenes by a condensation of salicylaldehyde and
dimedone/cyclohexane-1,3-dione. The use of water as a solvent, simple work-up procedure
and no need of catalyst make it not only eco-friendly but also economical alternative to
earlier reported approaches.
Experimental:
Various salicyldehydes (Sigma-Aldrich), 1,3-diketones viz cyclohexane-1,3-
dione (Alfa Aesar) and dimedone (Thomas Baker) were used as received.
IR spectra were recorded on Perkin-Elmer [FT-IR-783] spectrophotometer.
NMR spectra were recorded on Bruker AC-200 or MSL-300 (200 MHz for 1H NMR
and 50 MHz for 13 C NMR) spectrometer in CDCl3 using TMS as an internal standard
and δ values are expressed in ppm.
Column chromatography was performed on silica gel (60-120 mesh, Qualigens).
Melting points recorded are uncorrected.
General Procedure:
Catalyst-free synthesis of 1-oxo- hexahydroxanthenes :
A suspension of a salicylaldehyde (1mmol) and dimedone / cyclohexane-1,3-
dione (2 mmol) in water (5 mL) was stirred at reflux condition and the progress of the
reaction was monitored by TLC. After completion of the reaction, the resulting solid
product was collected by filtration and purified by recrystalization from 95 % ethanol.
These products were characterized by spectral techniques. (i.e. IR, 1H and 13C NMR,
LCMS).
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
229
Spectral Data: 9-(2-Hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-3,3-dimethyl-2,3,4,9-tetrahydro-
xanthen-1-one: (entry 3a, Table 1)
O
HO OO
Mp. 240 oC, IR (KBr): 3188, 2954, 1630, 1594,
1489, 1374, 1241, 1188, 755 cm-1; 1H NMR (300
MHz, CDCl3): δ 10.50 (s, 1H), 7.16 (m, 1H, J = 8.1
Hz), 7.01 (m, 3H, J = 8.1 Hz and J = 2.1 Hz), 4.66 (s,
1H), 2.31-2.63 (m, 6H),1.90-2.03 (m, 2H), 1.12(s,
3H), 1.08(s, 3H), 1.03(s,3H), 0.99(s, 3H)
7-Hydroxy-9-(2-hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-3,3- dimethyl-2,3,4,9-
tetrahydro-xanthen-1-one : (entry 3e, Table 1)
O
HO OO
HO
Mp 217 oC; IR (KBr): 3110, 2958, 2926, 1589,
1468, 1382, 1230, 1192, 1034, 820 cm-1; 1H-NMR
(DMSO-d6, 300 MHz): δ d 10.29 (bs, 1H), 9.07
(s,1H), 6.74 (d, 1H, J = 8.7 Hz), 6.45 (dd, 1H, J = 8.7
Hz and J = 2.7 Hz), 6.37 (d, 1H, J = 2.7 Hz), 4.95(s,
1H), 1.96-2.49 (m, 8H), 1.01(s, 3H), 0.95 (s, 3H),
0.88 (s, 6H); 13C-NMR (DMSO-d6, 75 MHz): δ
26.64, 29.69, 32.01, 41.21, 50.90, 99.98, 110.38,
114.10, 114.37, 116.39, 116.78, 126.72, 143.12,
154.10, 165.40, 195.54, 196.12; EIMS : m/z 382
(M+).
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
230
6-hydroxy-9-((2-hydroxy-6-oxocyclohex-1-enyl))-2,3,4,9-tetrahydro-1H-xanthen-1-one :
(entry 3k, Table 1)
Mp. 240 oC, IR (KBr):3339, 3190, 2954, 1624, 1589,
1456, 1378, 1231, 1189, 1139, 987 cm-1; 1H NMR
(300 MHz, DMSO-d6): δ d 10.35 (bs,1H),9.38 (s,
1H), 6.74(d,1H, J = 8.1 Hz), 6.39 (dd, 1H, J = 8.1 Hz
and J =2.1 Hz), 6.29 (d,1H, J = 2.1 Hz), 4.92 (s, 1H),
1.65-2.21 (m, 12H); 13CMR (75 MHz, DMSO-d6,):
20.75, 20.85, 25.21, 27.73, 37.13, 99.98, 102.19,
112.27, 112.80, 116.45, 120.00,129.26,150.55,
156.55, 166.96,196.54 EIMS: m/z 326 (M+).
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
231
SPECTRAS
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
232
Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous Medium
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