Xanthene derivatives and ortho-substituted phenols - Products from dehydrogenation of acyclic 1,5-diketones

Article abstract of DOI:10.1007/s10593-006-0004-7

Xanthene derivatives and ortho-substituted phenols were obtained during the dehydrogenation of 1,5-diketones and their ketol forms at a Pt/C catalyst at 280-320°C. 2005 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-006-0004-7

Chemistry of Heterocyclic Compounds, Vol. 41, No. 11, 2005
XANTHENE DERIVATIVES AND ortho-
SUBSTITUTED PHENOLS – PRODUCTS FROM
DEHYDROGENATION OF ACYCLIC 1,5-DIKETONES
T. I. Akimova, V. A. Kaminsky, and I. V. Svistunova
Xanthene derivatives and ortho-substituted phenols were obtained during the dehydrogenation of
1,5-diketones and their ketol forms at a Pt/C catalyst at 280-320°C.
Keywords: 1,5-diketones, ketols, ortho-substituted phenols, xanthenes, xanthones, catalytic
dehydrogenation.
The dehydrogenation of 1,5-diketones with six-membered rings can be regarded as a fairly simple
method for the transition to aromatic compounds – derivatives of diarylmethanes or xanthenes. There is one
paper on this subject in the literature [1], but the problem has not been investigated systematically.
We studied the catalytic dehydrogenation of the diketone 1 and its ketol 1a and also the ketols 2a and 3a
substituted in the methane fragment and the diketones 4-8 substituted at the α-CH2 position on a Pt/C catalyst.
Dehydrogenation was conducted in an airtight closed flask, the outlet of which was placed in a
measuring cylinder filled with water. This made it possible to judge the intensity of the release of hydrogen and
its volume in various temperature ranges. The process was conducted at the temperatures at which active release
of hydrogen was observed without substantial resinification of the reaction mixture.
Theoretically the dehydrogenation of 1,5-diketones can take place in two directions: A) with the
formation of xanthene and its derivatives; B) with the formation of phenol derivatives of diphenylmethane
(bisphenols). The experiment showed that the main products of this reaction are derivatives of xanthene and
ortho-substituted phenols, and their ratio depends on the structure of the initial compound. Bisphenols were not
obtained. The ortho-substituted phenols either result from retro-Michael dissociation of the initial diketones or
are the products from dissociation of the bisphenols.
We traced the effect of the substituent in the methane fragment on the direction of dehydrogenation for
the case of the ketones 1a-3a. An increase in the yield of the xanthene was observed with increase in the size of
the substituent. Thus, the xanthene 9 and the phenol 17 were obtained with approximately identical yields
(32 and 35% respectively) from the ketol 1a, the xanthene 10 was obtained from the ketol 2a with a yield of
65%, and the hydrogenation of the ketol 3a led to an almost quantitative yield of the xanthene compounds 11
and 15. We suppose that the reason for this is the previously described effect of a bulky substituent on the
transformation of a 1,5-diketone into a conformation in which the carbonyl groups are sterically close, thereby
facilitating dehydrogenation by path A [2].
__________________________________________________________________________________________
Far-East State University, Vladivostok, Russia; e-mail: chem@deans.dvgu.ru. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 11, pp. 1637-1643, November, 2005. Original article submitted July 6,
2000.
1374
0009-3122/05/4111-1374©2005 Springer Science+Business Media, Inc.

R
R
R
O
Б
А
O O
OH
OH
R1
OH
R1
R1
R1
R1
R1
1–8
R
R
R
O
O
R1
1 OH
OH OH
R1
R1
R1
R1
R
9–14
1a–3a
1, 1а, 4-9, 12-14 R = H; 2, 2a, 10 R = Me; 3, 3a, 11 R = Ph; 1-3, 1a-3a, 9-11 R1 = H;
4 R1 = cyclohexyl; 5 R1 = cyclohexylidene, 6 R1 = 1-chlorocyclohexyl,
7 R1 = PhCH=; 8 R1 = p-MeOC6H4CH=; 12 R1 = cyclohexyl; 13 R1 = PhCH2;
14 R1 = p-MeOC6H4CH2
Dehydrogenation of the diketones 4-6 gives one and the same xanthene 12. Under the elevated
temperature conditions the chloro ketone is clearly dehydrochlorinated with the formation of an isomeric mixture
of ketones 4 and 5 [3] followed by migration of the double bond (cyclohexenyl and then cyclohexylidene) to the
cyclohexanone ring and dehydrogenation to compound 12. The latter is converted by oxidation with chromic
anhydride into the xanthone 22.
O
4
8
1
9
Ph
3
5
2
3
7
6
2
6
10
OH
OH
1
CH2
8
O
4
5
7
CH2
O
15
CH2
11CH2
12
9
13
14
10
O
11
15
16
R
R
R
17, 18
19, 20
O
R
R1
21, 22
17, 19 R = H; 18, 20 R = p-MeO; 21 R = H, R1 = CH2Ph; 22 R = R1 = cyclohexyl
During dehydrogenation of the arylidene ketones 7 and 8 appreciable amounts (up to 14%) of the
xanthones 19-21 were unexpectedly obtained in addition to the xanthenes 13 and 14 and the phenols 17 and 18.
We suppose that they are formed by addition of the water released during the reaction to the intermediate
fragment of the α,β-unsaturated ketone A, formed during dehydrogenation at positions 2 and 3 of the initial
1,5-diketone structure and stabilized by the arylidene fragment, with the subsequent probable formation of the
4-hydroxy-4H-pyran structure B and final dehydrogenation of the latter to the xanthone structure C.
1375

OH
O
OH
O
3
2
+ H2O
– H2O
4
1
5
O
O
O
O
A
OH
C
B
In the case of the arylidene ketones 7 and 8, as also during dehydrogenation of the α-cycloalkyl
diketones 4-6, the exo double bond also migrates into the carbonyl-containing ring, but as a result of the
increased stability of the arylidene C=C bond migration takes place with greater difficulty, and the addition of
water to the intermediate A becomes competitive.
1
The structures of the compounds were confirmed by the data from the IR, mass, and H and 13C NMR
spectra (Tables 1 and 2) and also by comparison with the spectra of the authentic substances (xanthene and
xanthone) and published data [4].
The mixture of compounds 11 and 15, which have practically identical Rf values and solubility but form
crystals of different shapes, was separated by selecting the crystals according to shape. The ratio of these
compounds in the reaction mixture was established from the intensity ratio of the signals for the benzyl protons
H-9 (a singlet at 5.25 ppm for compound 11 and a doublet at 3.65 ppm for compound 15). This corresponded to
TABLE 1. The Characteristics and IR Spectra of Compounds 12-16 and 18-
22
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp, °С*
IR spectrum, ν, cm-1
С
Н
12
13
14
15
16
18
С25H30O
С27H22O
С29H26O3
С19H20O
С13H18O
С14H14O2
86.39
86.70
8.40
8.67
193-194
95-96
1586, 1480 (Ph); 1253, 1236,
1210 (C–O)
89.50
89.36
6.07
5.95
1601, 1578, 1486, 1456 (Ar);
1265, 1117, 1094 (C–O)
82.46
82.21
6.16
6.04
98-100
110-112
61-62
1610, 1584, 1510, 1456 (Ar);
1247, 1217, 1178, 1037 (C–O)
81.60
81.81
7.36
7.57
1500, 1590, 1600 (Ph); 1260,
1190, 1120 (C–O)*2
82.34
82.10
9.25
9.47
3620, 3480 (OH), 1610, 1590
(Ph); 1260, 1230, 1170 (C–O)*2
78.50
78.33
6.54
6.38
62-64
3354 (OH); 1608, 1594,
1508 (Ph); 1259, 1240, 1180,
1028 (C–O)
19
20
21
22
С27H20O2
С29H24O4
С20H14O2
С25H28O2
86.41
86.17
5.48
5.32
184-186
146-148
140-142
185-186
1660 (C=O); 1597, 1493 (Ph);
1215 (C–O)
79.98
79.82
5.67
5.50
1657 (C=O); 1597, 1512 (Ar);
1248, 1216 (Ph–O)
1656 (C=O); 1615, 1601 (Ph);
1224 (C–O)
83.78
83.92
5.13
4.90
83.17
83.33
8.39
7.95
1659 (C=O); 1609, 1490 (Ph);
1240, 1213, 1147 (C–O)
_______
*Solvents for recrystallization: chloroform (compound 12), 2:1 ethanol–
benzene (compound 13), petroleum ether (compounds 14 and 16), ethanol
(compounds 15, 20, and 22), 5:1 petroleum ether–benzene (compound 18),
3:1 benzene–petroleum ether (compound 19), and 2:1 benzene–ethanol
(compound 21).
*2 In carbon tetrachloride.
1376

1377

1378

a ratio of 6:1 for compounds 11-15. The trans coupling of the hydrogenated rings in the structure of compound
15 follows from the nature of the signal for the H-4a proton, shifted upfield on account of its proximity to the
heteroatom – a triplet of doublets at 3.85 ppm with J = 10 and J = 1 Hz.
The IR spectra of compounds 19-22 have the carbonyl absorption characteristic of xanthones in the
region of 1656-1660 cm-1.
EXPERIMENTAL
The IR spectra were recorded in potassium bromide on a Perkin-Elmer Spectrum BX-II instrument. The
mass spectra were recorded on a Hewlett-Packard HP 5972 MSD/HP 5890 Series II GC instrument. The 1H and
13C NMR spectra were recorded on a Bruker AC-250 spectrometer (250 and 62 MHz respectively in
deuterochloroform) with TMS as internal standard. The Pt/C catalyst was prepared by the procedure described in
[5], and the Pt content was 8%.
Catalytic Dehydrogenation of Compounds 1-8 (General Procedure). The diketone or ketol was
rubbed with the catalyst in a ratio of 20:1 by weight for the ketones 1a-3a and 10:1 for the diketones 1, 4-8 and
transferred to a flask the outlet of which was placed in a measuring cylinder filled with water and turned upside
down into a crystallizer containing water. The flask was lowered into a metal bath heated to 160°C, and the
temperature was raised while the released gas was collected in the measuring cylinder. Two temperature ranges
for active release of gas were observed: 1) 280-300°C for compounds 1a-3a, 240-280°C for the diketones 4-6,
300-320°C for the diketones 7 and 8; 2) 340-360°C for all the compounds. In the last case the process is
accompanied by strong resinification of the reaction mixture, and dehydrogenation was therefore conducted in
the first temperature range for all the compounds except for the diketone 1, for which the second range was
investigated. Heating was continued until the release of hydrogen had stopped (2-4 h), and usually 60-80% of
the theoretical amount of gas calculated for the corresponding xanthene was collected. After cooling the reaction
mixture was mixed with chloroform, the catalyst was filtered off, the filtrate was dried with magnesium sulfate,
and the solvent was distilled.
1. The oily residue obtained from the ketol 1a (8 g, 0.038 mol) was distilled under vacuum, and 5.5 g of
distillate (bp 105-120°C, 1 mm Hg), which crystallized on cooling, was obtained. The distillate was mixed with
10% aqueous sodium hydroxide solution (50 ml), and the undissolved crystalline part was filtered off, washed
with acidified water, to pH 7 with water, and with ethanol (2 ml). We obtained 2.1 g (32%) of the xanthene 9;
mp 99-100°C (ethanol). It was identified by its Rf value, IR spectrum, and a mixed melting test with an authentic
sample of the xanthene. To the alkaline filtrate with vigorous stirring we added dropwise benzoyl chloride (7 ml,
0.05 mol) over 2 h (monitored by TLC). The oil that separated was extracted with ether (3 × 15 ml), and the
extract was washed with acidified water and then with water to pH 7 and dried with magnesium sulfate. After
distillation of the ether the residue was crystallized from ethanol, and 3.9 g of 2-benzylphenol benzoate was
obtained; mp 28°C. It was identified by its IR, mass, and NMR spectra. This amount corresponds to 2.49 g
(35%) of 2-benzylphenol (17).
2. From the ketol 2a (8 g, 0.036 mol) we obtained 5.7 g of a distillate boiling at 96-101°C (1 mm Hg)
that did not crystallize on cooling. During preparative separation on plates with SiO2 (100:250 µ) in the 2:1
hexane–ether system we obtained 4.6 g (65%) of 9-methylxanthene (10); bp 96-98°C (1 mm Hg). According to
data in [5], the boiling point is 95-97°C (0.3 mm Hg). The structure was confirmed by data from the IR and mass
spectra.
3. From the ketol 3a (5.5 g, 0.0176 mol) we obtained 4.4 g of a crystallization residue, representing a
mixture of two substances with identical Rf values (on Silufol plates in various systems) and identical solubility
but having a different crystal form – needle and cubic. From an alcohol solution of the mixture after free
evaporation by selecting the crystals we isolated 9-phenylxanthene (11) (colorless cubes) with mp 144-145°C
1379

(ethanol) (mp 145°C [5]) and 9-phenyl-1,2,3,4,4a,9a-hexahydroxanthene (15) (colorless needles). The ratio of
1
compounds 11 and 15 was 6:1 (according to the H NMR spectrum). Accordingly, the yield of the xanthene 11
amounted to 3.77 g (83%), and that of compound 15 to 0.63 g (14%).
4. We dehydrogenated the diketone 1 (6 g, 0.028 mol) at 340-360°C. The residue (5.8 g) partly
crystallized, and 2.0 g (38%) of the xanthene 9 was filtered off. The remaining part was separated on a column
of SiO2 (neutral) with elution first with petroleum ether (70-100°C) and then with a 50:1 mixture of petroleum
ether and ether (or ethyl acetate). We obtained a further 1.4 g (26%) of the xanthene 9 (total yield 65%) and
0.2 g (3.6%) of 2-(cyclohexylmethyl)phenol (16).
5. The residue obtained after dehydrogenation of the diketone 6 (1 g, 0.0027 mol) crystallized. We
separated 0.3 g (38.2%) of 4,5-dicyclohexylxanthene 12.
6. From the diketone 7 (6.2 g, 0.016 mol) we obtained 5.8 g of a residue. It was mixed with ether
(10 ml), and 4,5-dibenzylxanthone (19) (0.5 g) was filtered off. The remaining part was separated on a column as
described in expt. 4 with silica gel as sorbent. We obtained 1.5 g (26%) of 4,5-dibenzylxanthene (13), 1.3 g
(22%) of 2-benzylphenol (17), 0.3 g of xanthone 19 (total yield 14%), and 0.3 g (7%) of 4-benzylxanthone (21).
Similarly from the diketone 8 (7.2 g, 0.016 mol) we obtained 1.6 g (24%) of 4,5-di(p-
methoxybenzyl)xanthene (14), 1.4 g (20%) of 2-(p-methoxybenzyl)phenol (18), and 0.9 g (13%) of 4,5-di(p-
methoxybenzyl)xanthone (20).
4,5-Dicyclohexylxanthone (22). To a suspension of the xanthene 12 (0.8 g, 0.0023 mol) in acetic acid
(20 ml) we added dropwise over 10 min a solution of chromium(VI) oxide (1.8 g, 0.18 mol) in water (2 ml) with
acetic acid (4 ml). The mixture was stirred at 60°C for 6 h until the initial xanthene had disappeared (TLC) and
cooled. The precipitate was filtered off, and 0.6 g (72%) of compound 22 was obtained.
REFERENCES
1.
2.
C. Parrera and J. Pascual, An. Quim. Real. Soc. Esp. Fis. y Quim., 64, 729 (1968); Ref. Zh. Khim.,
18Zh221 (1970); 4Zh162 (1969).
N. V. Vershinina, V. I. Vysotskii, L. M. Eremeeva, V. A. Kaminskii, and M. N. Tilichenko, Khim.
Geterotsikl. Soedin., 1315 (1977).
3.
4.
T. I. Akimova and M. N. Tilichenko, Zh. Org. Khim., 26, 1249 (1990).
V. I. Glyzin, G. G. Nikolaeva, and T. D. Dargaeva, Natural Xanthones [in Russian], Nauka, Sib. Otd.,
Novosibirsk (1968).
5.
6.
V. I. Isagulyants and T. M. Egorova, Chemistry of Petroleum [in Russian], Khimiya, Moscow,
Leningrad (1971).
Dictionary of Organic Compounds, Chapman and Hall, New York, London, Toronto (1982).
1380