Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous

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


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


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.


212

Fabaceae Compositae

Blumea riparia

Pic.1

Fig. 6


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].


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.


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.


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.


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.


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


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


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.


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.


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.


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.


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


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


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


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+).


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).


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+).


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+).


231

SPECTRAS


232


233


234


235


236


237


238


239


240


241


242

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Chapter 6: Uncatalyzed Synthesis of Hexahydroxanthenes in Aqueous

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