Facile approach for the synthesis of 2,3,4,9-tetrahydro-1H-xanthen-1-ones and 8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-ones via trapping of o-quinone methides

Article abstract of DOI:10.1080/00397911.2010.545164

An efficient, simple synthesis of 2,3,4,9-tetrahydro-1H-xanthene-1-ones and 8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-ones is reported by one-pot condensation of 3-dimethylamino-2-cyclohexen-1-ones with hydroxybenzyl alcohols, phenol, and 2-naphthol Mannich bases or their quaternized derivatives. The mechanism of the reaction is believed to involve the formation of the o-quinone methide intermediate. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.545164

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Facile Approach for the Synthesis of
2,3,4,9-Tetrahydro-1H-xanthen-1-
ones and 8,9,10,12-Tetrahydro-11H-
benzo[a]xanthen-11-ones via Trapping of
o-Quinone Methides
Vitaly A. Osyanin a , Elena A. Ivleva a & Yuri N. Klimochkin a
a Organic Chemistry Division, Samara State Technical University,
Samara, Russia
Available online: 16 Nov 2011
To cite this article: Vitaly A. Osyanin, Elena A. Ivleva & Yuri N. Klimochkin (2012): Facile Approach
for the Synthesis of 2,3,4,9-Tetrahydro-1H-xanthen-1-ones and 8,9,10,12-Tetrahydro-11H-
benzo[a]xanthen-11-ones via Trapping of o-Quinone Methides, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 42:12, 1832-1847
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Synthetic Communications1, 42: 1832–1847, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.545164
FACILE APPROACH FOR THE SYNTHESIS OF
2,3,4,9-TETRAHYDRO-1H-XANTHEN-1-ONES AND
8,9,10,12-TETRAHYDRO-11H-BENZO[a]XANTHEN-
11-ONES VIA TRAPPING OF o-QUINONE METHIDES
Vitaly A. Osyanin, Elena A. Ivleva, and Yuri N. Klimochkin
Organic Chemistry Division, Samara State Technical University,
Samara, Russia
GRAPHICAL ABSTRACT
Abstract An efficient, simple synthesis of 2,3,4,9-tetrahydro-1H-xanthene-1-ones and
8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-ones is reported by one-pot condensation
of 3-dimethylamino-2-cyclohexen-1-ones with hydroxybenzyl alcohols, phenol, and
2-naphthol Mannich bases or their quaternized derivatives. The mechanism of the reaction
is believed to involve the formation of the o-quinone methide intermediate.
Keywords Enamines; hydroxybenzyl alcohols; Mannich bases; o-quinone methides;
8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-ones; 2,3,4,9-tetrahydro-1H-xanthen-1-
ones
INTRODUCTION
Compounds containing a xanthene skeleton are important biologically active
heterocyclic compounds, which may possess antiviral,[1] antimicrobial,[2] anti-
inflammatory,[3] anticonvulsant,[4] and antimalarial[5,6] activities. These compounds
are also employed as dyes[7] (fluorescein, eosin, rhodamines), pH-sensitive
fluorescent materials for visualization of biomolecules,[8] and linkers.[9] A great
number of highly functionalized xanthenes occurs in nature. Some examples are
the antibiotic rhodomyrtone[10] and a-glucosidase inhibitor myrtucommulones[11]
(Scheme 1). Thus, the synthesis of a variety of xanthene derivatives is desirable.
Received October 5, 2010.
Address correspondence to Vitaly A. Osyanin, Organic Chemistry Division, Samara State
Technical University, Samara, Russia. E-mail: vosyanin@mail.ru
1832

TETRAHYDRO-1H-XANTHENONES
1833
Scheme 1. Some tetrahydro-1H-xanthen-1-ones embodied in natural products.
o-Quinone methides (o-QMs) are important intermediates in many chemical and
biological processes. These reactive species are efficient DNA alkylating and
cross-linking agents and play a key role in the biological action of several antibiotics
such as mitomycin and anthracyclines. o-QMs act as heterodienes in inter- and
intramolecular cycloadditions with olefins to give various substituted chromanes. Like
vinyl ketones, o-QMs also act as acceptors in Michael additions to afford ortho-
substituted phenols.[12] Most of the methods for generating o-QMs involve high-
temperature thermolysis and=or use of highly derivatized or structurally complex pre-
cursors. Much attention has been devoted to the development of methods to generate
o-QMs photochemically, because this provides temporal and spatial control over their
formation and subsequent reaction to give chroman products.[13,14]
Only some examples of the reactions of o-QMs with enamines leading to the
xanthenes derivatives are described.[15–20] Herein, we report a new procedure for
the synthesis of 2,3,4,9-tetrahydro-1H-xanthen-1-ones and 8,9,10,12-tetrahydro-
1H-benzo[a]xanthen-11-ones from enamines (1a,b) and o-QMs generated from
corresponding salicylic alcohols, Mannich bases, or quarternary ammonium salts.
It should be noted that the synthetic potential of the o-hydroxybenzyl alcohols
and Mannich bases for a o-QM formation has remained largely underestimated in
relation to the high temperature needed for the thermal elimination of the amine or
water. The formation of quaternary ammonium salts by alkylation of the Mannich
adducts is a way to induce easier removal of the amino residue and, therefore, trapping
of the transient electrophilic species at lower temperature. Furthermore, elimination of
the tertiary amines as an ammonium salt makes the process irreversible.[21]
RESULTS AND DISCUSSION
Initially, we investigated the condensation reaction of salicylic alcohol and
dimedone enamine 1b in dioxane, ethanol, and acetonitrile at reflux. However, no
products were detected. Then, it was decided to carry out the reaction in refluxing
dimethylformamide (DMF), and it was found that the reaction proceeded smoothly,
giving 2,3,4,9-tetrahydro-1H-xanthene-1-one 3c in 75% isolated yield.
To explore the scope and limitation of this reaction and to generalize the
procedure, a variety of electronically divergent o-benzo- and naphthoquinone
methide precursors 2a–j, and 4a–d were examined (Scheme 2), and the results are

1834
V. A. OSYANIN, E. A. IVLEVA, AND Y. N. KLIMOCHKIN
Scheme 2. Synthesis of xanthene derivatives. R ¼ R1 ¼ R2 ¼ H (3a); R ¼ R1 ¼ H, R2 ¼ Br (3b); R ¼ CH3,
R1 ¼ R2 ¼ H (3c); R ¼ CH3, R1 ¼ H, R2 ¼ COCH3 (3d); R ¼ CH3, R1 ¼ NO2, R2 ¼ 1-Ad (3e); R ¼ CH3,
R1 ¼ Br, R2 ¼ 1-Ad (3f); R ¼ CH3, R1 ¼ H, R2 ¼ 1-Ad (3g); R ¼ CH3, R1 ¼ H, R2 ¼ NO2 (3h); R ¼ CH3,
R1 ¼ H, R2 ¼ C(CH3)3 (3i); R ¼ R2 ¼ CH3, R ¼ R2 ¼ CH3, R1 ¼ 1-Ad (3j); R1 ¼ R1 ¼ R2 ¼ H (5a);
R1 ¼ R3 ¼ H, R2 ¼ 1-Ad (5b); R1 ¼ H, R2 ¼ R3 ¼ 1-Ad (5c); R1 ¼ Ph, R2 ¼ R3 ¼ H (5d)
summarized in Table 1. In all cases, quaternized derivatives of phenolic Mannich
bases, o-hydroxybenzyl alcohols, and 2-naphthol Mannich bases carrying either an
electron-withdrawing group or an electron-donating group reacted successfully
and gave the products 3a–j and 5a–d in good yields. Compounds 3a–d were prepared
=
from o-hydroxybenzyl alcohols 2a–d (X OH), 3e,f from Mannich bases 2e,f,
=
=
([X N(CH3)2]) and 3g–j from Mannich base methiodides 2g–j (X N(CH3)3I). The
reactions were performed in refluxing DMF at sufficiently high temperature to
ensure the thermal decomposition of the o-QM precursors. Products can be easily
purified by single recrystallization. The reaction was repeated on several different
scales (up to 50 mmol), all with comparable yields.
In the reaction of enamine 1b with 2,4-dihydroxy-3-morpholin-4-yl-methylace-
tophenone, only 7-acetyl-8-hydroxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-
1-one 3k was isolated (Scheme 3). The structure of the product and the regioselectiv-
ity of this cycloaddition reaction were determined on the basis of a sharp, downfield
chemical shift (12.82 ppm) of the unreacted phenolic proton.
In the reactions with 2-naphthol Mannich bases, the better results probably
reflect the ease of formation of a o-QM adjacent to an aromatic ring as compared with
phenol Mannich bases in which formation of the o-QM implies the disappearance of
the only aromatic ring. It should be noted that none of the dimeric nor trimeric pro-
ducts that are obtained in the usual pyrolytic methods were detected.
Attempts to extend this reaction to the 2-dimethylaminomethyl-4-nitrophenol,
however, failed, perhaps because of the relatively greater thermal stability of this

TETRAHYDRO-1H-XANTHENONES
1835
Table 1. 2,3,4,9-Tetrahydro-1H-xanthen-1-ones 3a–k and 8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-
ones 5a–d
Compound
Yield (%)a
Mp (lit. mp) ꢁC
Solvent for recrystallization
3a
3b
3c
3d
3e
3f
75
55
53
56
81
82
60
68
59
60
61
89
91
86
90
89–90 (90–91[22]
131–132
)
Acetic acid–water
Ethanol
DMF
94–95 (80[23]
144–145
196–198
)
Methanol
DMF–water
DMF
220–222
226–227
3g
3h
3i
DMF
127–129 (116[23]
150–152
238–240
)
DMF–water
DMF–water
Toluene
3j
3k
5a
5b
5c
5d
147–149
157–158
Ethanol
Ethanol
281–282
>330
151–153 (149–150[24]
DMF
DMF
Ethanol
)
aIsolated yield.
phenolic Mannich base and consequent difficulty in generating the o-QM under the
conditions mentioned in this article. Nevertheless, in the reaction with quaternized
2-dimethylaminomethyl-4-nitrophenol 2h, which is more reactivity precursor of o-
QM, corresponding xanthene derivative 3h was prepared in 68% yield.
On the basis of these results, this process was then extended to a heterocyclic
precursor of o-QM. From 5-dimethylaminomethyl-6-hydroxy-2,3,4,9-tetrahydro-
1H-b-carbolin-1-one 6 and enamine 1b a novel heterocyclic system, 1,5,6,7,8,9,10,
11,12,13-decahydrochromeno[3,2-g]b-carboline 7 was prepared in 73% yield. In a
similar manner, 3,6-bis(morpholinomethyl)catechol 8 reacts with 2 equivalents of
enamine 1b in refluxing DMF to yield a novel fused heterocyclic system 1,2,3,4,5,8,9,
10,11,12-decahydrochromeno[3,2-c]xanthene 9.
Structural assignment was based on elemental analyses and absence of an
1
OH-band in the infrared (IR) and of the phenolic proton signal in the H NMR
spectrum of the xanthenes derivatives 3a–j, 5a–d, 7, and 9, respectively. The IR spec-
tra show the presence of a conjugated carbonyl group (tmax 1637–1654 cmꢀ1). In the
aliphatic region of the H NMR spectra of compounds 3c–j and 5a–c, two charac-
1
teristic 2-H singlets are present at d 2.30–2.42 and 2.41–2.58 ppm corresponding to
Scheme 3. Synthesis of 7-acetyl-8-hydroxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (3k).

1836
V. A. OSYANIN, E. A. IVLEVA, AND Y. N. KLIMOCHKIN
Scheme 4. Plausible mechanism for the synthesis of xanthene-based compounds.
the methylene protons of the carbocyclic fragment and 6-H singlet at 1.10–1.21 ppm
corresponding methyl groups. The benzylic protons appear as 2-H singlets at
1
3.46–3.81 ppm. In the H NMR spectrum of compound 5d, two 3-H singlets at d
0.94 and 1.10 ppm were assigned to the diastereotopic protons of the methyl groups.
In the majority of cases, the most intensive peak in the mass spectrum corresponds to
the molecular ion peak.
A mechanistic rationale portraying the probable sequence of events is given in
Scheme 4. We suppose that the reaction proceeds via the o-quinone methide
intermediate, which is formed by the thermal desamination of the Mannich bases
or their methiodides, or dehydratation of the hydroxybenzyl alcohols. Subsequent
cycloaddition of the o-QMs with 3-dimethylamino-2-cyclohexen-1-ones affords the
hemiaminal, which is desaminated to give the xanthene derivative. The driving force
of the reaction is the resulting rearomatization of the molecule.
In these reactions, the o-QM reacts as electron-deficient heterodiene. Its
reaction with electron-rich enamines proceeds regioselectively 50 that the carbon
connected with dimethylamino group reacts with the quinone methide oxygen and
the neighboring vinylic carbon reacts with the methylene carbon of the QM. The
regioselectivity can be readily explained by ionic resonance forms of the coreactants
or alternatively in terms of the frontier orbital interaction of the lowest unoccupied
molecular orbital (LUMO) of a QM and the highest occupied molecular orbital
(HOMO) of an enamine. At the same time, the possibility of a Michael-type addition
of the enamine to the QM to give zwitterionic intermediate, which is cyclized and
then desaminated, must not be ruled out.[25]
CONCLUSION
We have developed a facile protocol for the synthesis of 2,3,4,9-tetrahydro-
1H-xanthen-1-ones and 8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-ones. Their
synthesis by the suggested procedure does not require an excess of any reagents or
the use of any catalysts, and it can be performed under neutral reaction conditions.
Besides, the advantages of this method include the use of available reagents, simple
workup procedure, easy isolation, absence of oligomeric products, and high purity

TETRAHYDRO-1H-XANTHENONES
1837
and good yields of the xanthene derivatives. The method is general for o-QM
precursors containing both electron-withdrawing and electron-donating substituents
and is compatible with considerable structural variation on both the phenol and
enamine units.
EXPERIMENTAL
FTIR spectra were taken on a Shimadzu FTIR-8400S spectrophotometer in
KBr pellets. NMR spectra were recorded on a Brucker AM 400-MHz spectrometer
in CDCl3 using tetramethylsilane (TMS) as an internal reference. Chemical shifts
and coupling constants were recorded in units of parts per million (ppm) and hertz
(Hz), respectively. Melting points were determined on an Electrothermal melting-
point apparatus and are uncorrected. Elemental analyses were performed on a
EuroVector EA-3000 instrument. Electron impact–mass spectrometry (EI-MS) spec-
tra were obtained on a Finnigan Trace DSQ spectrometer (70 eV). Thin-layer chro-
matography (TLC) was carried out on aluminium-backed silica-gel plates (Merck
60 F254) with visualization of components by ultraviolet light (254 nm) or exposure
to I2. Noncommercial o-hydroxybenzyl alcohols, Mannich bases, and their
methiodides were prepared according to well-known methods.[26–28]
4-(1-Adamantyl)-2-nitrophenol (10)
A solution of 7 ml 94% HNO3 in 60 ml of glacial acetic acid was added to a
suspension of 40 g (0.18 mol) of 4-(1-adamantyl)phenol in 600 ml of glacial acetic
acid dropwise under vigorous stirring at room temperature. The reaction mixture
was stirred for 30 min and poured into crushed ice, and the precipitate was separated
by filtration and washed with water until the washings were neutral. The crude
product was purified by recrystallization from acetic acid to give 44 g (67%) of yellow
1
crystals, mp 108–109 ꢁC. H NMR (CDCl3), d, ppm: 1.71–1.81 (m, 6H, 3CH2 Ad),
1.85–1.87 (m, 6H, 3CH2 Ad), 2.10 (br. s, 3H, 3CHAd), 7.08 (d, J ¼ 8.7 Hz, 1H,
H-6), 7.61 (dd, J ¼ 8.7 Hz, J ¼ 2.3 Hz, 1H, H-5), 8.01 (d, J ¼ 2.3 Hz, 1H, H-3),
10.45 (s, 1H, OH); 13C NMR (CDCl3), d, ppm: 28.81 (CH), 35.87 (C), 36.56
(CH2), 43.02 (CH2), 119.55 (CH), 120.93 (CH), 133.33 (C), 135.09 (CH), 144.09
(C), 153.18 (C); IR, n, cmꢀ1: 3178, 3089 (OH), 2904, 2846 (CHAd), 1623, 1585
=
(C C), 1531 (NO2), 1488, 1361, 1326 (NO2), 1265, 1141, 1103, 837; EI-MS
(70 eV) m=z (% int.): 273 (Mþ, 65), 230 (26), 216 (84), 170 (100), 152 (54), 141
(46), 128 (60), 115 (93). Anal. calcd. for C16H19NO3: C, 70.31; H, 7.01; N, 5.12.
Found: C, 70.28; H, 6.97; N, 5.16.
4-(1-Adamantyl)-2-[(dimethylamino)methyl]-6-nitrophenol (2e)
Dimethylamine (8 ml of 33% aqueous solution, 0.053 mol) and formaldehyde
(4 ml of 37% aqueous solution, 0.053 mol) were added to a solution of 12 g
(0.044 mol) of 10 in 100 ml ethanol. The reaction mixture was refluxed for 48 h
and then cooled to room temperature. The precipitate that formed was filtered,
washed in ice-cold ethanol, and purified by recrystallization from ethanol to give
1
8 g (57%) of orange crystals, mp 86–87 ꢁC. H NMR (CDCl3), d, ppm: 1.67 (br. s,

1838
V. A. OSYANIN, E. A. IVLEVA, AND Y. N. KLIMOCHKIN
6H, 3CH2 Ad), 1.78 (br. s, 6H, 3CH2Ad), 2.00 (br. s, 3H, 3CHAd), 2.39 [s, 6H,
(CH3)2N], 3.86 (s, 2H, CH2), 4.79 (s, 1H, OH), 7.35 (d, J ¼ 2.2 Hz, 1H, H-3), 7.61
(d, J ¼ 2.2 Hz, 1H, H-5); 13C NMR (CDCl3), d, ppm: 28.83 (CH3), 35.72 (CH2),
36.60 (C), 43.09 (CH2), 44.59 (CH), 61.18 (CH2), 121.00 (CH), 125.40 (C), 132.04
(CH), 135.92 (C), 141.91 (C), 152.12 (C); IR, n, cmꢀ1: 3421, 3097 (OH), 2904,
=
2846 (CHAd), 1623 (C C), 1539 (NO2), 1469, 1377, 1342 (NO2), 1261, 1176, 1130,
840; EI-MS (70 eV) m=z (% int.): 330 (Mþ, 82), 312 (Mþ–H2O, 100), 286 [Mþ–
(CH3)2N, 10], 269 (83), 135 (Adþ, 27), 58 (92). Anal. calcd for C19H26N2O3: C,
69.07; H, 7.93; N, 8.48. Found: C, 69.02; H, 7.97; N, 8.52.
4-(1-Adamantyl)-2-bromo-6-[(dimethylamino)methyl)phenol (2f)
Dimethylamine (3 ml of 33% aqueous solution, 0.02 mol) and formaldehyde
(1.5 ml of 37% aqueous solution, 0.02 mol) were added to a solution of 5.53 g
(0.018 mol) of 4-(1-adamantyl)-2-bromophenol in 50 ml ethanol. The reaction
mixture was stirred at room temperature for 48 h. The precipitate that formed was
then filtered, washed in ice-cold ethanol, and purified by recrystallization from etha-
nol to give 4.39 g (67%) of colorless crystals, mp 180–182 ꢁC (dec). 1H NMR
(CDCl3), d, ppm: 1.69–1.77 (m, 6H, 3CH2 Ad), 1.83 (br. s, 6H, 3CH2 Ad), 2.06 (br.
s, 3H, 3CHAd), 2.32 [s, 6H, (CH3)2N], 3.62 (s, 2H, CH2), 6.86 (s, 1H, H-5), 7.36
(s, 1H, H-3), 8.62 (br. s, 1H, OH); 13C NMR (CDCl3), d, ppm: 29.02 (CH3), 35.63
(C), 36.79 (CH2), 43.40 (CH2), 44.45 (CH), 63.20 (CH2), 109.88 (C), 122.32 (C),
123.92 (CH), 128.59 (CH), 143.35 (C), 152.50 (C); IR, n, cmꢀ1: 3244 (OH), 2958,
=
2904, 2846 (CHAd), 1608, 1577 (C C), 1427, 1353, 1257, 1122, 1103, 837; EI-MS
(70 eV) m=z (% int.): 365 (Mþ þ 2, 92), 363 (Mþ, 100), 284 (Mþ–Br, 12), 239 (13),
170 (16), 135 (Adþ, 30). Anal. calcd. for C19H26BrNO: C, 62.64; H, 7.19; N, 3.84.
Found: C, 62.59; H, 7.22; N, 3.87.
5-(1-Adamantyl)-2-hydroxybenzyl(trimethyl)ammonium Iodide (2g)
Dimethylamine (3 ml of 33% aqueous solution, 0.02 mol) and formaldehyde
(1.5 ml of 37% aqueous solution, 0.02 mol) were added to a solution of 4.1 g
(0.018 mol) of 4-(1-adamantyl)phenol in 30 ml ethanol. The reaction mixture was
stored at room temperature for 48 h and at ꢀ20 ꢁC for 2 h. The precipitate formed
was filtered, washed in ice-cold methanol, and dissolved in 20 ml of CH3I. The
resulting solution was refluxed for 12 h. After cooling to 0 ꢁC, the precipitate that
formed was filtered, and washed in ice-cold diethyl ester to give 5 g (65%) of colorless
crystals, mp 201–203 ꢁC. 1H NMR (DMSO-d6), d, ppm: 1.65–1.73 (m, 6H, 3CH2Ad),
1.78–1.82 (m, 6H, 3CH2Ad), 2.02 (br. s, 3H, 3CHAd), 2.99 [s, 9H, (CH3)3N], 4.40 (s,
2H, CH2), 6.88 (d, J ¼ 8.4 Hz, 1H, H-3), 7.30 (dd, J ¼ 8.4 Hz, J ¼ 2.5 Hz, 1H, H-4),
7.32 (d, J ¼ 2.5 Hz, 1H, H-6), 10.01 (br. s, 1H, OH); 13C NMR (DMSO-d6), d, ppm:
28.84 (CH3), 35.54 (C), 36.69 (CH2), 43.28 (CH2), 52.58 (CH), 64.04 (CH2), 114.53
(C), 116.22 (CH), 128.82 (CH), 131.74 (CH), 142.34 (C), 155.50 (C); IR, n, cmꢀ1
3182 (OH), 2901 (CHAd), 2847 (CHAd), 1612 (C C), 1512, 1477, 1420, 1261, 1130,
1107, 879. Anal. calcd. for C20H30INO: C, 56.16; H, 7.02; N, 3.28. Found: C,
56.21; H, 6.97, N, 3.32.
:
=

TETRAHYDRO-1H-XANTHENONES
1839
2-Hydroxy-5-nitrobenzyl(trimethyl)ammonium Iodide (2h)
A solution of 5 g (0.0255 mol) of 2-dimethylaminomethyl-4-nitrophenol and
7.24 g (0.051 mol) of CH3I in 100 ml ethanol was refluxed for 2 h. After cooling to
ꢀ20 ꢁC, the precipitate formed was filtered and washed in ice-cold ethanol to give
7.33 g (85%) of yellow crystals, mp 232–234 ꢁC (dec). 1H NMR (DMSO-d6), d,
ppm: 3.05 [s, 9H, N(CH3)3], 4.52 (s, 2H, CH2), 7.10 (d, J ¼ 8.8 Hz, 1H, H-3), 8.23
(dd, J ¼ 8.8 Hz, J ¼ 1.4 Hz, 1H, H-4), 8.36 (d, J ¼ 1.4 Hz, 1H, H-6), 11.92 (br. s,
1H, OH); 13C NMR (DMSO-d6), d, ppm: 52.82 (CH3), 62.47 (CH2), 116.22 (C),
117.24 (CH), 128.47 (CH), 131.50 (CH), 139.97 (C), 164.22 (C); IR, n, cmꢀ1
3200–2800 (OH), 1616, 1593 (C C), 1520 (NO2), 1493, 1342 (NO2), 1296, 1277,
1088, 891. Anal. calcd. for C10H15IN2O3: C, 35.50; H, 4.44; N, 8.28. Found: C,
35.55; H, 4.39, N, 8.31.
:
=
3-(1-Adamantyl)-2-hydroxy-5-methylbenzyl(trimethyl)ammonium
Iodide (2j)
Dimethylamine (3 ml of 33% aqueous solution, 0.02 mol) and formaldehyde
(1.5 ml of 37% aqueous solution, 0.02 mol) were added to a solution of 4 g
(0.017 mol) of 2-(1-adamantyl)-4-methylphenol in 30 ml ethanol. The reaction
mixture was stored at room temperature for 48 h and at ꢀ20 ꢁC for 2 h. The precipi-
tate that formed was filtered, washed in ice-cold methanol and dissolved in 20 ml of
CH3I. The resulting solution was refluxed for 12 h. After cooling to 0 ꢁC, the precipi-
tate that formed was filtered and washed in ice-cold diethyl ester to give 5.5 g (60%)
of colorless crystals, mp 217–219 ꢁC. 1H NMR (DMSO-d6), d, ppm: 1.70 (br. s, 6H,
3CH2Ad), 2.01 (br. s, 3H, 3CHAd), 2.05 (br. s, 6H, 3CH2Ad), 2.22 (s, 3H, CH3), 2.95
[s, 9H, (CH3)3N], 4.49 (s, 2H, CH2), 7.00 (s, 1H, Harom.), 7.08 (s, 1H, Harom.), 8.59 (s,
1H, OH); 13C NMR (CDCl3), d, ppm: 20.80 (CH3), 29.01 (CH3), 36.96 (CH2), 37.00
(C), 40.93 (CH2), 48.29 (CH), 64.28 (CH2), 115.82 (C), 130.33 (C), 131.04 (CH),
132.32 (CH), 139.60 (C), 153.61 (C); IR, n, cmꢀ1: 3387, 3190 (OH), 2901, 2847
=
(CHAd), 1609 (C C), 1462, 1269, 1211, 1180, 1011, 872, 756. Anal. calcd. for
C21H32INO: C, 57.08; H, 7.25; N, 3.17. Found: C, 56.98; H, 7.29; N, 3.21.
6-(1-Adamantyl)-1-[(dimethylamino)methyl)-2-naphthol (4b)
Dimethylamine (3 ml of 33% aqueous solution, 0.02 mol) and formaldehyde
(1.5 ml of 37% aqueous solution, 0.02 mol) were added to a solution of 5 g
(0.018 mol) of 6-(1-adamantyl)-2-naphthol[29] in 50 ml ethanol. The reaction mixture
was refluxed for 5 min, cooled to room temperature, and stored at 25 ꢁC overnight
and at ꢀ15 ꢁC for 48 h. The precipitate formed was then filtered, washed in ice-cold
methanol, and purified by recrystallization from ethanol–DMF to give 6.1 g (83%) of
1
colorless crystals, mp 177–178 ꢁC. H NMR (CDCl3), d, ppm: 1.77–1.85 (m, 6H,
3CH2Ad), 1.96–2.04 (m, 6H, 3CH2Ad), 2.14 (br. s, 3H, 3CHAd), 2.41 [s, 6H,
(CH3)2N], 4.09 (s, 2H, CH2), 7.08 (d, J ¼ 8.7 Hz, 1H, Harom.), 7.53 (dd, J ¼ 8.7 Hz,
J ¼ 1.8 Hz, 1H, H-7), 7.65 (d, J ¼ 1.8 Hz, 1H, H-5), 7.67 (d, J ¼ 8.7 Hz, 1H, Harom.),
7.78 (d, J ¼ 8.7 Hz, 1H, Harom.), 9.91 (br. s, 1H, OH); 13C NMR (CDCl3), d, ppm:
29.07 (CH3), 36.00 (C), 36.96 (CH2), 43.24 (CH2), 44.79 (CH), 57.98 (CH2),

1840
V. A. OSYANIN, E. A. IVLEVA, AND Y. N. KLIMOCHKIN
111.30 (C), 119.12 (CH), 120.84 (CH), 123.97 (CH), 124.45 (CH), 128.54 (C), 129.27
(CH), 130.80 (C), 145.28 (C), 156.33 (C); IR, n, cmꢀ1: 3051 (OH), 2908, 2885, 2850
=
(CHAd), 1604 (C C), 1512, 1423, 1338, 1276, 1149, 844; EI-MS (70 eV) m=z (% int.):
335 (Mþ, 100), 290 [Mþ–NH(CH3)2, 60], 233 (23), 215 (16), 165 (10), 152 (5), 44 (47).
Anal. calcd. for C23H29NO: C, 82.34; H, 8.71; N, 4.18. Found: C, 82.39; H, 8.67; N,
4.21.
5-Dimethylaminomethyl-6-hydroxy-2,3,4,9-tetrahydro-1H-b-
carbolin-1-one (6)
Dimethylamine (4.5 ml of 33% aqueous solution, 0.03 mol) and formaldehyde
(2.3 ml of 37% aqueous solution, 0.03 mol) were added to a suspension of 5 g
(0.025 mol) of 6-hydroxy-2,3,4,9-tetrahydro-1H-b-carboline-1-one in 20 ml ethanol.
The reaction mixture was stirred at room temperature overnight. The precipitate
formed was then filtered and washed ice-cold ethanol to give 4.7 g (73%) of color-
less crystals, mp 160–162 ꢁC (dec). 1H NMR (DMSO-d6), d, ppm: 2.77 [s, 6H,
(CH3)2N], 3.07 (t, J ¼ 6.9 Hz, 2H, CH2), 3.45–3.49 (m, 2H, CH2N), 4.43 [s, 2H,
CH2N(CH3)2], 6.93 (d, J ¼ 8.7 Hz, 1H, Harom.), 7.33 (d, J ¼ 8.7 Hz, Harom.), 7.61
(s, 1H, NHamide), 9.38 (br. s, 1H, OH), 11.61 (s, 1H, NHindole); 13C NMR
(DMSO-d6), d, ppm: 22.84 (CH2), 41.52 (CH2), 43.15 (CH3), 53.41 (CH2),
106.95 (C), 114.86 (CH), 115.86 (CH), 116.50 (C), 123.31 (C), 129.24 (C), 132.44
(C), 151.30 (C), 162.06 (C); IR, n, cmꢀ1: 3410, 3279, 3248 (NH=OH), 2974,
=
2719, 1639 (C O), 1585, 1547, 1516, 1462, 1431, 1369, 1346, 1304, 1242, 1211,
1165, 1138, 1076, 941, 806, 775, 660; EI-MS (70 eV) m=z (% int.): 259 (Mþ, 16),
214 [Mþ – NH(CH3)2, 70], 185 (28), 157 (15), 129 (12), 102 (5), 44 (100). Anal.
calcd for C14H17N3O2: C, 64.85; H, 6.61; N, 16.20. Found: C, 64.72; H, 6.68;
N, 16.29.
General Experimental Procedure for the Synthesis of the
2,3,4,9-Tetrahydro-1H-xanthen-1-ones and 8,9,10,12-Tetrahydro-1H-
benzo[a]xanthen-11-ones
A mixture of 0.84 g (6 mmol) of 3-dimethylamino-2-cyclohexen-1-one 1a or
1 g (6 mmol) of 3-dimethylamino-5,5-dimethyl-2-cyclohexen-1-one 1b[30] and
6 mmol of the appropriate o-quinone methide precursor (hydroxybenzyl alcohol,
phenol or 2-naphthol Mannich base, Mannich base methiodide) in DMF (10 ml)
was refluxed for 4 h and then stored at ꢀ10 ꢁC overnight. The precipitate that
formed was then filtered, washed ice-cold ethanol, and purified by recrystallization.
If the precipitate was not formed, the reaction mixture was poured into 50 ml of
cold water to yield a solid product, which was filtered, washed with water, dried,
and recrystallized.
Characterization Data of the 2,3,4,9-Tetrahydro-1H-xanthen-1-ones
and 8,9,10,12-Tetrahydro-1H-benzo[a]xanthen-11-ones
2,3,4,9-Tetrahydro-1H-xanthen-1-one (3a). Slightly brown crystals; 1H
NMR, d, ppm: 2.06 (qui, J ¼ 6.5 Hz, 2H, CH2-3), 2.46 (t, J ¼ 6.7 Hz, 2H, CH2),

TETRAHYDRO-1H-XANTHENONES
1841
2.56 (t, J ¼ 6.2 Hz, 2H, CH2), 3.51 (s, 2H, CH2-Ar), 6.96 (d, J ¼ 8.0 Hz, 1H, H-5),
7.05 (dd, J ¼ 7.8 Hz, J ¼ 6.7 Hz, 1H, H-7), 7.14–7.17 (m, 2H, H-6,8); 13C NMR, d,
ppm: 20.70 (CH2), 21.22 (CH2), 27.79 (CH2), 36.73 (CH2), 110.10 (C), 116.49
(CH), 120.91 (C), 124.71 (CH), 127.68 (CH), 129.79 (CH), 149.86 (C), 167.18 (C),
198.48 (C); IR, n, cmꢀ1: 3036 (CHarom.), 2943, 2874 (CHaliph.), 1639 (C O), 1581
=
=
(C C), 1493, 1454, 1393, 1250, 1234, 1184, 1134, 995, 995, 852, 760; EI-MS
(70 eV) m=z (% int.): 200 (Mþ, 100), 199 (Mþ–H, 84), 183 (Mþ–OH, 12), 172
(Mþ–CO, 14), 171 (Mþ–H–CO, 15), 157 (9), 144 (70), 137 (7), 128 (7), 115 (41). Anal.
calcd. for C13H12O2, %: C, 77.98; H, 6.04. Found, %: C, 78.05; H, 5.98.
7-Bromo-2,3,4,9-tetrahydro-1H-xanthen-1-one (3b). Colorless crystals;
1H NMR, d, ppm: 2.07 (dd, J ¼ 12.5 Hz, J ¼ 5.9 Hz, 2H, CH2), 2.46 (t, J ¼ 6.7 Hz,
2H, CH2), 2.53–2.58 (m, 2H, CH2), 3.48 (s, 2H, CH2-Ar), 6.84 (d, J ¼ 8.1 Hz, 1H,
H-5), 7.26 (d, J ¼ 8.1 Hz, 1H, H-6), 7.27 (s, 1H, H-8); 13C NMR, d, ppm: 20.62
(CH2), 21.18 (CH2), 27.68 (CH2), 36.70 (CH2), 109.70 (C), 117.01 (C), 118.26
(CH), 123.19 (C), 130.69 (CH), 132.36 (CH), 148.98 (C), 166.63 (C), 197.94 (C);
IR, n, cmꢀ1: 3059 (CHarom.), 2947, 2885 (CHaliph.), 1639 (C O), 1574 (C C),
1481, 1423, 1381, 1234, 1184, 1138, 1111, 1065, 999, 864, 825; EI-MS (70 eV) m=z
(% int.): 280 (Mþ þ 2, 64), 278 (Mþ, 68), 277 (Mþ–H, 32), 261 (Mþ–OH, 8), 250
(Mþ–CO, 10), 249 (Mþ–H–CO, 6), 222 (52), 199 (Mþ–Br, 10), 171 (12), 142 (18),
115 (100). Anal. calcd. for C13H11BrO2, %: C, 55.94; H, 3.97. Found, %: C, 55.85;
H, 4.05.
=
=
3,3-Dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (3c). Yellow crystals;
1H NMR, d, ppm: 1.12 [s, 6H, C(CH3)2], 2.32 (s, 2H, CH2), 2.42 (s, 2H, CH2),
3.51 (s, 2H, CH2-Ar), 6.95 (d, J ¼ 8.1 Hz, 1H, H-5), 7.05 (t, J ¼ 8.1 Hz, 1H, H-7),
7.15 (d, J ¼ 8.1 Hz, 1H, H-8), 7.16 (t, J ¼ 8.1 Hz, 1H, H-6); 13C NMR, d, ppm:
21.10 (CH2), 28.51 (CH3), 32.23 (C), 41.55 (CH2), 50.68 (CH2), 108.82 (C), 116.56
(CH2), 120.88 (C), 124.70 (CH2), 127.70 (CH2), 129.83 (CH2), 149.96 (C), 165.32
(C), 198.19 (C); IR, n, cmꢀ1: 3047 (CHarom.), 2959, 2932, 2889, 2870 (CHaliph.),
=
=
1639 (C O), 1582 (C C), 1493, 1458, 1393, 1246, 1231, 1180, 768; EI-MS (70 eV)
m=z (% int.): 228 (Mþ, 100), 227 (Mþ–H, 28), 213 (Mþ–CH3, 33), 200 (Mþ–CO,
8), 195 (Mþ–CH3– H2O, 21), 185 (Mþ–CH3– CO, 30), 171 (25), 158 (21), 144 (47),
115 (42). Anal. calcd. for C15H16O2, %: C, 78.87; H, 7.02. Found, %: C, 78.92; H,
7.10.
7-Acetyl-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (3d). Brown
1
crystals; H NMR, d, ppm: 1.10 [s, 6H, C(CH3)2], 2.30 (s, 2H, CH2), 2.41 (s, 2H,
CH2), 2.53 (s, 3H, CH3CO), 3.51 (s, 2H, CH2-Ar), 6.98 (d, J ¼ 8.9 Hz, 1H, H-5),
7.73 (s, 1H, H-8), 7.75 (d, J ¼ 8.9 Hz, 1H, H-6); 13C NMR, d, ppm: 21.03 (CH2),
26.56 (CH3), 28.45 (CH3), 32.20 (C), 41.28 (CH2), 50.60 (CH2), 108.89 (C), 116.79
(CH), 121.04 (C), 128.35 (CH), 130.54 (CH), 133.65 (C), 153.44 (C), 164.61 (C),
196.70 (C), 197.78 (C); IR, n, cmꢀ1: 3061 (CHarom.), 2962, 2934, 2899, 2874
=
=
=
(CHaliph.), 1680 (C O), 1637 (C O), 1582 (C C), 1499, 1421, 1383, 1366, 1273,
1232, 1177, 1150, 1119, 1103, 1026, 1016, 959, 833; EI-MS (70 eV) m=z (% int.):
270 (Mþ, 100), 255 (Mþ–CH3, 39), 237 (Mþ–CH3– H2O, 18), 227 (Mþ–CH3– CO,
33), 213 (19), 200 (14), 199 (22), 186 (29), 171 (22), 143 (12), 115 (19). Anal. calcd.
for C17H18O3, %: C, 75.55; H, 6.66. Found, %: C, 75.51; H, 6.71.

1842
V. A. OSYANIN, E. A. IVLEVA, AND Y. N. KLIMOCHKIN
7-(1-Adamantyl)-3,3-dimethyl-5-nitro-2,3,4,9-tetrahydro-1H-xanthen-1-
1
one (3e). Yellow crystals; H NMR, d, ppm: 1.11 [s, 6H, C(CH3)2], 1.71–1.80 (m,
6H, 3CH2Ad), 1.86 (s, 6H, 3CH2Ad), 2.10 (br. s, 3H, 3CHAd), 2.32 (s, 2H, CH2),
2.48 (s, 2H, CH2), 3.54 (s, 2H, CH2-Ar), 7.34 (d, 2H, J ¼ 2.2 Hz, H-8), 7.66 (d,
1H, J ¼ 2.2 Hz, H-6); 13C NMR, d, ppm: 21.32 (CH2), 28.43 (CH3), 28.73 (CH),
32.31 (C), 36.18 (C), 36.48 (CH2), 41.10 (CH2), 42.97 (CH2), 50.69 (CH2), 109.06
(C), 120.46 (CH), 123.16 (C), 131.09 (CH), 138.63 (C), 140.82 (C), 147.92 (C),
164.42 (C), 197.66 (C); IR, n, cmꢀ1: 2912, 2847 (CHaliph.), 1650 (C O), 1574
=
=
(C C), 1535 (NO2), 1381, 1346 (NO2), 1281, 1219, 1188, 1169, 1142, 1034; EI-MS
(70 eV) m=z (% int.): 407 (Mþ, 100), 392 (Mþ–CH3, 12), 374 (Mþ–CH3– H2O, 2),
364 (Mþ–CH3– CO, 11), 323 (6), 165 (13), 135 (Adþ, 10). Anal. calcd. for
C25H29NO4, %: C, 73.71; H, 7.13; N, 3.43. Found, %: C, 73.69; H, 7.19; N, 3.38.
7-(1-Adamantyl)-5-bromo-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-
1-one (3f). Yellow crystals; 1H NMR, d, ppm: 1.10 [s, 6H, C(CH3)2], 1.69–1.78 (m,
6H, 3CH2Ad), 1.82 (s, 6H, 3CH2Ad), 2.07 (br. s, 3H, 3CHAd), 2.30 (s, 2H, CH2), 2.48
(s, 2H, CH2), 3.50 (s, 2H, CH2-Ar), 7.03 (d, J ¼ 2.2 Hz, 2H, H-8), 7.34 (d, J ¼ 2.2 Hz,
1H, H-6); 13C NMR, d, ppm: 21.89 (CH2), 28.46 (CH3), 28.87 (CH), 32.28 (C), 36.00
(C), 36.64 (CH2), 41.30 (CH2), 43.15 (CH2), 50.74 (CH2), 109.12 (C), 110.50 (C),
121.98 (C), 125.39 (CH), 128.37 (CH), 144.71 (C), 149.04 (C), 165.08 (C), 197.91
(C); IR, n, cmꢀ1: 2954, 2897, 2847 (CHaliph.), 1654 (C O), 1566 (C C), 1470,
1381, 1219, 1169, 1146, 1018, 853; EI-MS (70 eV) m=z (% int.): 442 (Mþ þ 2, 98),
440 (Mþ, 100), 425 (Mþ–CH3, 6), 399 (Mþ–CH3– H2O, 4), 397 (Mþ–CH3– CO,
4), 356 (7), 220 (7), 165 (5), 135 (Adþ, 8). Anal. calcd. for C25H29BrO2, %: C,
68.02; H, 6.58. Found, %: C, 67.97; H, 6.63.
=
=
7-(1-Adamantyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (3g).
Yellow crystals; 1H NMR, d, ppm: 1.11 [s, 6H, C(CH3)2], 1.72–1.87 (m, 6H,
3CH2Ad), 1.87 (s, 6H, 3CH2Ad), 2.09 (br. s, 3H, 3CHAd), 2.32 (s, 2H, CH2), 2.41
(s, 2H, CH2), 3.51 (s, 2H, CH2-Ar), 6.90 (d, J ¼ 8.3 Hz, 1H, H-5), 7.12 (d, J ¼ 2.2 Hz,
1H, H-8), 7.16 (dd, J ¼ 8.3 Hz, J ¼ 2.2 Hz, 1H, H-6); 13C NMR, d, ppm: 21.40 (CH2),
28.49 (CH3), 28.97 (CH), 32.24 (C), 35.91 (C), 36.79 (CH2), 41.60 (CH2), 43.31
(CH2), 50.74 (CH2), 108.80 (C), 116.05 (CH), 120.13 (C), 124.25 (CH), 126.15
(CH), 147.83 (C), 148.05 (C), 165.35 (C), 198.10 (C); IR, n, cmꢀ1: 2901, 2847
=
=
(CHaliph.), 1647 (C O), 1589 (C C), 1497, 1381, 1261, 1231, 1219, 1169, 1146,
1122, 1107, 1018, 806; EI-MS (70 eV) m=z (% int.): 362 (Mþ, 100), 347 (Mþ–CH3,
20), 329 (Mþ–CH3– H2O, 5), 319 (Mþ–CH3– CO, 11), 305 (9), 292 (14), 278 (16),
221 (16), 135 (Adþ, 5). Anal. calcd. for C25H30O2, %: C, 82.87; H, 8.30. Found,
%: C, 82.81; H, 8.34.
3,3-Dimethyl-7-nitro-2,3,4,9-tetrahydro-1H-xanthen-1-one (3h). Yellow
1
crystals; H NMR, d, ppm: 1.12 [s, 6H, C(CH3)2], 2.33 (s, 2H, CH2), 2.45 (s, 2H,
CH2), 3.58 (s, 2H, CH2-Ar), 7.05 (d, J ¼ 8.8 Hz, 1H, H-5), 8.04 (d, J ¼ 8.8 Hz, 1H,
H-6), 8.06 (s, 1H, H-8); 13C NMR, d, ppm: 21.23 (CH2), 28.47 (CH3), 32.29 (C),
41.19 (CH2), 50.60 (CH2), 108.62 (C), 117.49 (CH), 122.25 (C), 123.74 (CH),
125.71 (CH), 144.24 (C), 154.51 (C), 164.26 (C), 197.53 (C); IR, n, cmꢀ1: 3040
=
=
(CHarom.), 2955, 2932 (CHaliph.), 1651 (C O), 1582 (C C), 1524 (NO2), 1385,
1342 (NO2), 1234, 1188, 1026, 748; EI-MS (70 eV) m=z (% int.): 273 (Mþ, 100),

TETRAHYDRO-1H-XANTHENONES
1843
258 (Mþ–CH3, 19), 240 (Mþ–CH3– H2O, 10), 230 (Mþ–CH3– CO, 28), 217 (16), 216
(12), 189 (34), 184 (21), 170 (15), 143 (16), 115 (31). Anal. calcd. for C15H15NO4, %:
C, 65.94; H, 5.50; N, 5.12. Found, %: C, 65.87; H, 5.55; N, 5.07.
3,3-Dimethyl-7-tert-butyl-2,3,4,9-tetrahydro-1H-xanthen-1-one
(3i).
1
Yellow crystals; H NMR, d, ppm: 1.10 [s, 6H, C(CH3)2], 1.28 [s, 9H, C(CH3)3],
2.30 (s, 2H, CH2), 2.40 (s, 2H, CH2), 3.49 (s, 2H, CH2-Ar), 6.87 (d, J ¼ 8.6 Hz,
1H, H-5), 7.13 (s, 1H, H-8), 7.16 (d, J ¼ 8.6 Hz, 1H, H-6); 13C NMR, d, ppm:
21.38 (CH2), 28.49 (CH3), 31.49 (CH3), 32.24 (C), 34.41 (C), 41.59 (CH2), 50.73
(CH2), 108.79 (C), 116.02 (CH), 120.09 (C), 124.69 (CH), 126.51 (CH), 147.73 (C),
147.82 (C), 165.35 (C), 198.07 (C); IR, n, cmꢀ1: 3063 (CHarom.), 2959, 2893, 2870
=
=
(CHaliph.), 1654 (C O), 1589 (C C), 1504, 1462, 1273, 1184, 1150, 1126, 1026,
822; EI-MS (70 eV) m=z (% int.): 284 (Mþ, 99), 283 (Mþ–H, 25), 269 (Mþ–CH3,
100), 256 (Mþ–CO, 4), 251 (Mþ–CH3– H2O, 6), 241 (Mþ–CH3– CO, 12), 227
(12), 200 (17), 185 (19), 141 (7), 115 (15). Anal. calcd. for C19H24O2, %: C, 80.28;
H, 8.47. Found, %: C, 80.24; H, 8.51.
5-(1-Adamantyl)-3,3,7-trimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one
1
(3j). Yellow crystals; H NMR, d, ppm: 1.13 [s, 6H, C(CH3)2], 1.77 (br. s, 6H,
3CH2Ad), 2.08 (br. s, 9H, 3CHAd, 3CH2Ad), 2.25 (s, 3H, CH3-Ar), 2.31 (s, 2H,
CH2), 2.47 (s, 2H, CH2), 3.46 (s, 2H, CH2-Ar), 6.79 (s, 1H, Harom.), 6.88 (s, 1H,
H
arom.); 13C NMR, d, ppm: 21.12 (CH3), 21.49 (CH2), 28.60 (CH3), 29.12 (CH),
32.28 (C), 36.94 (C), 37.13 (CH2), 41.11 (CH2), 41.51 (CH2), 50.78 (CH2), 108.56
(C), 120.91 (C), 125.93 (CH), 127.93 (CH), 133.57 (C), 137.36 (C), 146.86 (C),
164.68 (C), 197.95 (C); IR, n, cmꢀ1: 2955, 2905, 2851 (CHaliph.), 1655 (C O), 1593
=
=
(C C), 1458, 1389, 1215, 1169, 1146, 1119, 1034, 852; EI-MS (70 eV) m=z (% int.):
376 (Mþ, 100), 375 (Mþ–H, 22), 361 (Mþ–CH3, 11), 343 (Mþ–CH3– H2O, 3), 333
(Mþ–CH3– CO, 3), 306 (10), 292 (10). Anal. calcd. for C26H32O2, %: C, 82.97; H,
8.52. Found, %: C, 82.91; H, 8.57.
7-Acetyl-8-hydroxy-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one
(3k). Colorless crystals; 1H NMR, d, ppm: 1.11 [s, 6H, C(CH3)2], 2.31 (s, 2H,
CH2), 2.39 (s, 2H, CH2), 2.55 (s, 3H, CH3CO), 3.34 (s, 2H, CH2-Ar), 6.48 (d,
J ¼ 8.1 Hz, 1H, H-5), 7.55 (d, J ¼ 8.1 Hz, 1H, H-6), 12.82 (s, 1H, OH); 13C
NMR, d, ppm: 16.23 (CH2), 26.52 (CH3), 28.50 (CH3), 32.21 (C), 41.21 (CH2),
50.71 (CH2), 107.56 (CH), 109.34 (C), 110.06 (C), 115.98 (C), 129.97 (CH),
155.12 (C), 162.20 (C), 163.86 (C), 197.81 (C), 203.16 (C); IR, n, cmꢀ1: 2959,
=
=
2928, 1651 (C O), 1628, 1593 (C C), 1427, 1389, 1369, 1323, 1254, 1211, 1122,
1053, 1026, 818; EI-MS (70 eV) m=z (% int.): 286 (Mþ, 100), 285 (Mþ–H, 50),
271 (Mþ–CH3, 25). Anal. calcd. for C17H18O4, %: C, 71.31; H, 6.34. Found, %:
C, 71.27; H, 6.37.
9,9-Dimethyl-8,9,10,12-tetrahydro-1H-benzo[a]xanthen-11-one
(5a).
1
Pink crystals; H NMR, d, ppm: 1.15 [s, 6H, C(CH3)2], 2.37 (s, 2H, CH2), 2.48 (s,
2H, CH2), 3.78 (s, 2H, CH2-Ar), 7.15 (d, J ¼ 8.8 Hz, 1H, H-6), 7.46 (ddd, J ¼ 8.1 Hz,
J ¼ 6.9 Hz, J ¼ 1.2 Hz, 1H, H-3), 7.57 (ddd, J ¼ 8.3 Hz, J ¼ 6.9 Hz, J ¼ 1.5 Hz, 1H,
H-2), 7.70 (d, J ¼ 8.8 Hz, 1H, H-5), 7.80 (d, J ¼ 8.1 Hz, 1H, H-4), 7.90 (dd,
J ¼ 8.6 Hz, J ¼ 1.0 Hz, 1H, H-1); 13C NMR, d, ppm: 19.02 (CH2), 28.58 (CH3),
32.30 (C), 41.44 (CH2), 50.79 (CH2), 108.82 (C), 113.64 (C), 117.17 (CH), 123.24

1844
V. A. OSYANIN, E. A. IVLEVA, AND Y. N. KLIMOCHKIN
(CH), 125.08 (CH), 127.09 (CH), 128.35 (CH), 130.87 (C), 132.14 (C), 147.01 (C),
164.80 (C), 198.34 (C); IR, n, cmꢀ1: 3070 (CHarom.), 2959, 2935, 2889 (CHaliph.),
=
=
=
1647 (C O), 1596 (C C), 1620, 1597 (C C), 1512, 146, 1396, 1377, 1227, 1180,
1026, 810, 752; EI-MS (70 eV) m=z (% int.): 278 (Mþ, 100), 277 (Mþ–H, 54), 263
(Mþ–CH3, 28), 250 (Mþ–CO, 6), 245 (Mþ–CH3– H2O, 18), 235 (Mþ–CH3– CO,
15), 208 (29), 194 (47), 165 (72), 152 (13), 139 (10), 128 (12), 115 (7). Anal. calcd.
for C19H18O2, %: C, 82.01; H, 6.48. Found, %: C, 81.96; H, 6.53.
3-(1-Adamantyl)-9,9-dimethyl-8,9,10,12-tetrahydro-1H-benzo[a]xanthen-
1
11-one (5b). Pink crystals; H NMR, d, ppm: 1.16 [s, 6H, C(CH3)2], 1.78–1.85 (m,
6H, 3CH2Ad), 2.02 (s, 6H, 3CH2Ad), 2.14 (br. s, 3H, 3CHAd), 2.38 (s, 2H, CH2), 2.49
(s, 2H, CH2), 3.78 (s, 2H, CH2-Ar), 7.13 (d, J ¼ 8.8 Hz, 1H, Harom.), 7.67 (d,
J ¼ 8.8 Hz, 2H, Harom.), 7.70 (s, 1H, H-4), 7.87 (d, J ¼ 8.8 Hz, 1H, Harom.); 13C
NMR, d, ppm: 18.98 (CH2), 28.59 (CH3), 29.02 (CH), 32.29 (C), 36.31 (C), 36.90
(CH2), 41.49 (CH2), 43.19 (CH2), 50.81 (CH2), 108.80 (C), 113.34 (C), 116.90
(CH), 122.98 (CH), 123.46 (CH), 125.29 (CH), 128.35 (CH), 130.32 (C), 130.98
(C), 146.59 (C), 148.09 (C), 164.91 (C), 198.42 (C); IR, n, cmꢀ1: 3070, 3060
=
=
(CHarom.), 2955, 2901, 2847 (CHaliph.), 1647 (C O), 1624, 1601 (C C), 1396, 1231,
1188, 1173, 1150, 1018, 976, 887, 806; EI-MS (70 eV) m=z (% int.): 412 (Mþ, 100),
397 (Mþ–CH3, 14), 384 (Mþ–CO, 4), 379 (Mþ–CH3– H2O, 4), 369 (Mþ–CH3–
CO, 5), 342 (12), 328 (8), 178 (6), 135 (Adþ, 6). Anal. calcd. for C29H32O2, %: C,
84.46; H, 7.77. Found, %: C, 84.40; H, 7.82.
3,6-Di(1-adamantyl)-9,9-dimethyl-8,9,10,12-tetrahydro-1H-benzo[a]xan-
1
then-11-one (5c). Pink crystals; H NMR, d, ppm: 1.21 [s, 6H, C(CH3)2], 1.84
(br. s, 12H, HAd), 2.02 (br. s, 6H, HAd), 2.16 (br. s, 6H, HAd), 2.21 (br. s, 6H,
H
Ad), 2.42 (s, 2H, CH2), 2.58 (s, 2H, CH2), 3.81 (s, 2H, CH2-Ar), 7.60 (s, 1H,
H-5), 7.63 (d, J ¼ 8.1 Hz, 1H, H-2), 7.70 (s, 1H, H-4), 7.84 (d, J ¼ 8.1 Hz, 1H,
H-1); 13C NMR, d, ppm: 19.13 (CH2), 28.68 (CH3), 29.04 (CH), 29.15 (CH),
32.35 (C), 36.30 (C), 36.93 (CH2), 37.20 (CH2), 37.50 (C), 41.35 (CH2), 43.23
(CH2), 50.87 (CH2), 108.50 (C), 113.83 (C), 122.49 (CH), 123.46 (CH), 124.59
(CH), 125.18 (CH), 128.93 (C), 130.65 (C), 137.59 (C), 146.63 (C), 148.08 (C),
164.05 (C), 198.25 (C); IR, n, cmꢀ1: 2901, 2847 (CHaliph.), 1655 (C O), 1597
=
=
(C C), 1450, 1396, 1223, 1180, 1134, 1030, 976, 899, 802; EI-MS (70 eV) m=z
(% int.): 546 (Mþ, 8), 411 (Mþ–Ad, 6), 246 (Mþ ꢀ 2Ad ꢀ 2CH3, 10), 135 (Adþ,
100). Anal. calcd. for C39H46O2, %: C, 85.67; H, 8.48. Found, %: C, 85.72; H,
8.41.
9,9-Dimethyl-12-phehyl-8,9,10,12-tetrahydro-1H-benzo[a]xanthen-11-
1
one (5d). Colorless crystals; H NMR, d, ppm: 0.94 (s, 3H, CH3), 1.10 (s, 3H,
CH3), 2.20–2.31 (m, 2H, CH2), 2.55 (s, 2H, CH2), 5.70 (s, 1H, CHPh), 7.04 (dd,
J ¼ 7.4 Hz, J ¼ 7.3 Hz, 1H, Harom.), 7.16 (t, J ¼ 7.5 Hz, 2H, Harom.), 7.30–7.36 (m,
4H, Harom.), 7.41 (dd, J ¼ 8.2 Hz, J ¼ 1.2 Hz, 1H, Harom.), 7.73–7.76 (m, 2H, Harom.),
7.99 (d, J ¼ 8.3 Hz, 1H, Harom.); 13C NMR, d, ppm: 27.26 (CH3), 29.42 (CH3), 32.36
(C), 34.82 (CH), 41.50 (CH2), 51.00 (CH2), 114.36 (C), 117.16 (CH), 117.80 (C),
123.78 (CH), 125.01 (CH), 126.35 (CH), 127.12 (CH), 128.36 (CH), 128.50 (CH),
128.54 (CH), 128.95 (CH), 131.50 (C), 131.59 (C), 144.87 (C), 147.84 (C), 163.99
(C), 197.00 (C); IR, n, cmꢀ1: 3055, 3024 (CHarom.), 2955, 2885 (CHaliph.), 1651

TETRAHYDRO-1H-XANTHENONES
1845
=
=
(C O), 1630, 1597 (C C), 1450, 1373, 1227, 1184, 1169, 1142, 1030, 806, 748, 698;
EI-MS (70 eV) m=z (% int.): 354 (Mþ, 23), 277 (Mþ–C6H5, 100), 269 (4), 239 (4), 221
(22), 193 (14), 165 (25). Anal. calcd. for C25H22O2, %: C, 84.75; H, 6.22. Found, %:
C, 84.68; H, 6.27.
6,6-Dimethyl-1,5,6,7,8,9,10,11,12,13-decahydrochromeno[3,2-g]b-carbo-
line-8,13-dione (7). A mixture of 0.63 g (3.8 mmol) of 1b and 1 g (3.8 mmol) of 6 in
DMF (10 ml) was refluxed for 1 h. After completion, the reaction mixture was cooled
to room temperature, the precipitate that formed was filtered, washed in ice-cold
ethylacetate, and purified by recrystallization from DMF to give 0.93 g (73%) of pink
crystals, mp > 300 ꢁC. 1H NMR (DMSO-d6), d, ppm: 1.07 [s, 6H, C(CH3)2], 2.26 (s,
2H, CH2), 2.87 (s, 2H, CH2), 3.15 (t, J ¼ 6.9 Hz, 2H, CH2), 3.52 (td, J ¼ 6.9 Hz,
J ¼ 2.3 Hz, 2H, CH2), 3.73 (s, 2H, CH2-Ar), 6.88 (d, J ¼ 8.7 Hz, 1H, Harom.), 7.09
(br. s, 1H, NHamide), 7.23 (d, J ¼ 8.70 Hz, 1H, Harom.), 11.24 (br. s, 1H, NHindole);
13C NMR (DMSO-d6), d, ppm: 19.79 (CH2), 22.72 (CH2), 28.43 (CH3), 32.16 (C),
41.61 (CH2), 41.86 (CH2), 50.98 (CH2), 107.81 (C), 112.40 (CH), 112.87 (C),
114.71 (CH), 119.10 (C), 123.91 (C), 129.19 (C), 134.94 (C), 143.68 (C), 161.99
(C), 165.12 (C), 196.83 (C); IR, n, cmꢀ1: 3398, 3224 (NH), 2955, 2927, 2870
=
=
=
(CHaliph.), 1651 (C O), 1636 (C O), 1612 (C C), 1497, 1427, 1396, 1369, 1342,
1227, 1207, 1173, 1076, 1026, 806, 775; EI-MS (70 eV) m=z (% int.): 336 (Mþ,
100), 335 (Mþ–H, 55), 321 (Mþ–CH3, 20), 279 (10), 252 (22). Anal. calcd. for
C25H22O2, %: C71.43; H, 5.95; N, 8.32. Found, %: C, 71.37; H, 5.99; N, 8.36.
2,2,11,11-Tetramethyl-1,2,3,4,5,8,9,10,11,12-decahydrochromeno[3,2-c]-
xanthene-4,9-dione (9). A mixture of 2.07 g (6.7 mmol) of 8[31] and 2.23 g
(13.4 mmol) of 1b in DMF (15 ml) was refluxed for 10 h. After completion, the
reaction mixture was cooled to room temperature, and the precipitate that formed
was filtered, washed in ethanol, and purified by recrystallization from DMF to give
1
1.72 g (68%) of yellow crystals, mp 276–278 ꢁC. H NMR, d, ppm: 1.12 (s, 12H,
6CH3), 2.32 (s, 4H, 2CH2-3,10), 2.50 (s, 4H, 2CH2-1,12), 3.45 (s, 4H, 2CH2-Ar),
6.82 (s, 2H, Harom.); 13C NMR, d, ppm: 20.90 (CH2), 28.49 (CH3), 32.29 (C),
41.44 (CH2), 50.70 (CH2), 108.90 (C), 120.29 (C), 124.53 (CH), 138.27 (CH),
164.64 (CH), 197.96 (CH); IR, n, cmꢀ1: 2959, 2927, 2874 (CHaliph.), 1655 (C O),
=
1574, 1462, 1385, 1285, 1226, 1207, 1126, 1061, 814; EI-MS (70 eV) m=z (% int.):
378 (Mþ, 100), 377 (Mþ–H, 24), 363 (Mþ–CH3, 23), 335 (Mþ–CH3–CO, 15), 294
(23), 256 (32), 115 (32). Anal. calcd. for C24H26O4, %: C, 76.17; H, 6.92. Found,
%: C, 76.23; H, 6.88.
ACKNOWLEDGMENT
The study was financially supported by the federal program ‘‘Scientific and
Pedagogical Staff of Innovative Russia in 2009–2013’’ (Project N P1104).
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