Mass spectrometric studies of self-condensation products of cyclohexanone under alkaline conditions and synthesis of dodecahydrotriphenylene and triphenylene from easily available reactants

Article abstract of DOI:10.1007/s11172-014-0632-5

LC-MS was used to study products of cyclohexanone self-condensation under alkaline conditions. Improved methods (as compared to those described in the literature) for the preparation of dodecahydrotriphenylene and highly pure sublimed triphenylene were suggested based on the easily available and cheap reactants. Possible reasons of the low yield of the target dodecahydrotriphenylene in the step of oligomerization of cyclohexanone were identified.

Full text of DOI:10.1007/s11172-014-0632-5

Russian Chemical Bulletin, International Edition, Vol. 63, No. 7, pp. 1539—1542, July, 2014
1539
Mass spectrometric studies of selfꢀcondensation products of cyclohexanone
under alkaline conditions and synthesis of dodecahydrotriphenylene
and triphenylene from easily available reactants
I. S. Kovalev,a D. S. Kopchuk,a,b G. V. Zyryanov,a,b A. F. Khasanov,a V. L. Rusinov,a and O. N. Chupakhina,b
aUral Federal University named after the First President of Russia B. N. Yeltsin,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Eꢀmail: gvzyryanov@gmail.com
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
20 ul. S. Kovalevskoy, 620219 Ekaterinburg, Russian Federation.
Eꢀmail: chupakhin@ios.uran.ru
LCꢀMS was used to study products of cyclohexanone selfꢀcondensation under alkaline
conditions. Improved methods (as compared to those described in the literature) for the prepaꢀ
ration of dodecahydrotriphenylene and highly pure sublimed triphenylene were suggested based
on the easily available and cheap reactants. Possible reasons of the low yield of the target
dodecahydrotriphenylene in the step of oligomerization of cyclohexanone were identified.
Key words: triphenylene, cyclohexanone, trimerization, aromatization.
At the present time, triphenylene (1) and its derivaꢀ
tives are of considerable interest because of a possibility of
their application as a base for the preparation of electroluꢀ
minescent materials,1 discotic liquid
well known methods which use readily available reagents,
in particular, cyclohexanone.24,25
An approach to the preparation of dodecahydrotripheꢀ
nylene 2 by the reaction of cyclohexanone with an alkali
described by German authors26 seems the most promisꢀ
ing, since it compares favorably with other methods by the
absence of expensive reactants and catalysts (Scheme 1).
The triol 3 results from the reaction of cyclohexanone
with the alkali at room temperature and its subsequent
dehydration with orthophosphoric acid gives dodecaꢀ
hydrotriphenylene 2. We have chosen this procedure as
a basic one in the present work.
crystals,2,3 and as chemosensors and
sensor materials.4,5 Unsubstituted
triphenylene can be easily functionalꢀ
ized: in the literature, there are deꢀ
scribed methods for the preparation
of its monobromo,6,7 hexabromo,8,9
monoiodo derivatives,10 various acyl
derivatives,11,12 as well as triphenyleneꢀ2ꢀcarbaldehyde.13
Thus, triphenylene 1 is a key compound in the preparation
of a wide variety of its derivatives necessary for different
purposes. The present work is devoted to the development
of an approach to the synthesis of triphenylene 1 from
easily available reagents.
Scheme 1
A number of methods for the preparation of triꢀ
phenylene 1 are described in the literature. In particular,
a preparative synthesis of triphenylene can be accomꢀ
plished using aryne intermediates,14—17 crossꢀcoupling reꢀ
actions,18 metalꢀcatalyzed arylation,19,20 cyclization based
on 9,10ꢀphenanthrenequinone.21 These methods have
a disadvantage of very expensive starting reagents and catꢀ
alysts, as well as a necessity to purify triphenylene in order
to obtain highly pure product.
At the same time, one of the most promising methods
for the preparation of triphenylene is dehydrogenation22,23
of dodecahydro derivative in the presence of palladiumꢀ
onꢀcharcoal, which in turn can be obtained according to
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1539—1542, July, 2014.
1066ꢀ5285/14/6307ꢀ1539 © 2014 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 63, No. 7, July, 2014
Kovalev et al.
The authors of the work26 found that the cyclic trimer 3
was the only product of the reaction of cyclohexanone
with an alkali, whose existence was confirmed by IR spectroꢀ
scopy and elemental analysis.
However, attempted reproduction of this method
showed that oligomerization of cyclohexanone is accomꢀ
panied by the formation of considerably more complicatꢀ
ed mixture of products. It should be also noted that the
yields of dodecahydrotriphenylene 2 obtained by this proꢀ
cedure varied from low to moderate. To find possible reaꢀ
sons for this, we studied the composition of the reaction
mixtures formed upon oligomerization of cyclohexanone
by LCꢀMS.
Table 1. The LCꢀMS data for the reaction mixture obtained
upon oligomerization of cyclohexane under alkaline conditionsa
Comꢀ Chromatographic
MS,
m/z, [M + H]+
Molecular
formula
pound
separation
c

Iint
Found
Calculated
ret
/min (rel. units)
Dimers
4а
4b
5
19.7
17.2
17.2
114239
326589
6445
179.1436
179.1436
197.1532
179.1436
179.1436 C12H18
197.1536 C12H20O2
C
12H18
O
O
Trimers
According to the LCꢀMS data, the reaction mixture
obtained by treatment of cyclohexane with NaOH for three
days contains the following intermediate compounds: deꢀ
hydrated dimers of cyclohexanone 4 (two isomers), dimer
of cyclohexanone 5, and isomers of cyclohexanone trimers
with different degree of dehydration 3, 6, and 7 (Table 1,
Fig. 1, 2).
3
15.8
16.0
17.3
22.5
20.5
22.5
24.5
28.9
17703
17609
25190
8700
11660
47939
15084
13772
295.2236
295.2237
295.2233
277.2113
259.2042
259.2042
259.2039
259.2031
295.2268
C18H30O3
295.2268 C18H30O3
295.2268 C18H30O3
277.2162 C18H28O2
259.2056 C18H26
259.2056 C18H26
259.2056 C18H26
259.2056 C18H26
6
7
O
O
O
O
aReaction conditions: cyclohexanone : NaOH = 3.8 : 1, 20 C,
3 days.
bCalculated based on the mass spectrometric data.
cIntegral intensity.
mixtures at room temperature; heating gave lower yields
of the target triphenylene 1. We also found that cyclohexꢀ
anone dimers 4a,b and 5 are present in the reaction mixꢀ
ture in large amounts, whereas the starting cyclohexanone
is completely absent. To sum up, there are no precondiꢀ
tion for the formation of the trimer and, therefore, of
dodecahydrotriphenylene 2, whereas tetramer is present
a
The peaks [M + H]+ of compounds with m/z 179.1436
(compounds 4a,b) and m/z 259.2042 (compound 7) have
the highest integral intensities.
The starting cyclohexanone was absent in the reaction
mixture: the distillation of the reaction mixtures gave no
fraction with b.p. 155 C, and no [M + H]+ peak of cycloꢀ
hexanone with m/z 99.08 was observed according to the
LCꢀMS data.
15
20

ret/min
Analysis of trimeric products of condensation of cycloꢀ
hexanone 3 (three isomers), 6 and 7 (four isomers)
showed that, despite the presence of such products
(see Table 1) in the reaction mixture, the integral intenꢀ
sities of the peaks of these compounds are low, therefore,
a suggestion that the low yield of the reaction is exꢀ
plained by the parallel processes of trimerization, leadꢀ
ing to the products incapable of further cyclization to
dodecahydrotriphenylene 2, was not confirmed. It can
be supposed that the oligomerization reaction of cycloꢀ
hexanone is kinetically controlled, since the best results
were obtained after a prolonged standing of the reaction
b
15
20
ret/min
Fig. 1. Chromatography pattern of cyclohexane dimers 4a,b (a)
and 5 (b).

MS study of cyclohexane alkaline condensation
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 7, July, 2014
1541
is considerably higher than that in the methods deꢀ
scribed earlier.
a
In conclusion, in the present work we developed an
approach to the synthesis of highly pure sublimed triꢀ
phenylene starting from inexpensive commercially availꢀ
able reactants. LCꢀMS was used to study composition of
the mixture of products obtained upon oligomerization of
cyclohexanone in the presence of an alkali, possible reaꢀ
sons decreasing the yield of the target dodecahydrotriꢀ
phenylene in this step were identified. Taking into acꢀ
count commercial value of triphenylene, this method
seems promising, despite a moderate yield of the target
product.
15
20

ret/min
b
Experimental
15
20
25 ret/min
1
H and 13C NMR spectra were recorded on a Bruker Avanceꢀ
c
400 spectrometer (400 and 100 MHz, respectively) in CDCl3,
using Me4Si as an internal standard. Melting points were meaꢀ
sured on a Boetius heating stage. Electron impact mass spectra
(EI) were measured on a SHIMADZU GCMSꢀQP2010 Ultra
instrument.
The mass analyzer was a Bruker Daltonics (Bremen, Gerꢀ
many) MicrOTOFꢀQ II mass spectrometer with an electrospray
ionization source, a 6ꢀport divert valve and syringe pump
kd Scientific appliance with the flow rate 180 L h–1, and an
Agilent 1200 chromatograph with a diode array detector (DAD).
The instrument controls were performed with micrOTOFconꢀ
trol 2.3 patch 1 (Bruker Daltonics) software. The nominal resoꢀ
lution of the instrument was 17500. The instrument was operatꢀ
ed in the positive ion mode with m/z range 50—900 Da. A 6 point
external instrument mass scale was performed before each seꢀ
quence with lithium formate clustered by infusing 10 mmol L–1
of lithium hydroxide in a mixture of isopropanol—0.2% aqueous
formic acid (1 : 1, v/v). The chromatograph was equipped by an
Agilent Eclipse XDB C18 column (150×4.6 mm) and worked in
the gradient mode (eluent acetonitrile—water, from 5 to 95% of
acetonitrile in the channel B from 0 to 30 min at the flow rate
1.0 mL min–1).
Dodecahydrotriphenylene (2). Calcined anhydrous sodium
hydroxide (6 g, 0.15 mol) was added to anhydrous freshly disꢀ
tilled cyclohexanone (60 mL, 0.58 mol) and the mixture obꢀ
tained was stirred at room temperature for three days. Then,
water (150 mL) was added to the reaction mixture with stirring,
a precipitate was filtered off, washed with 10% aqueous HCl and
water, and dried. The mixture of intermediate products without
additional purification was added to polyphosphoric acid (40 g)
and stirred for 2 h at 150 C. Then, the reaction mixture was
mixed with anhydrous sodium sulfate (100 g), placed into
a Soxhlet extractor, and the product was continuously extracted
with light petroleum (b.p. 40—70 C). A precipitate was filtered
off, washed with hexane, and dried. The yield was 24 g (52%),
m.p. 229—231 C. Found (%): C, 89.88; H, 10.01. C18H24. Calꢀ
culated (%): C, 89.94; H, 10.06. 1H NMR, : 1.78 (m, 12 H,
ArCH2CH2); 2.58 (m, 12 H, ArCH2CH2). 13C NMR, : 23.23,
26.98, 132.77. MS (EI), m/z (%): 240 [M]+ (100).
20
25
30 ret/min
Fig. 2. Chromatography pattern of cyclohexane trimers 3 (a),
6 (b), and 7 (c).
in insignificant amount (one isomer with the low integral
intensity of the peak).
One of the major reasons of low efficiency of the proꢀ
cess can be a low rate of cyclization reaction of the openꢀ
chain trimer to the cyclic structure 3, as well as to its
dehydrated forms 6 and 7, which were also identified in
the reaction mixture.
We assume that in order to increase the yield of the
target dodecahydrotriphenylene 2, it is necessary to periꢀ
odically add the starting cyclohexanone to the reaction
mixture and to increase reaction time.
It should be also noted that, despite considerable
amount of side products formed in the first step of the
process, the modified procedure used by us allows obtainꢀ
ing dodecahydrotriphenylene 2 with sufficient purity withꢀ
out additional purification.
We further made a number of changes in the procedure
used for the preparation of dodecahydrotriphenylene 2 (the
dehydration step). In particular, we used polyphosphoric
acid instead of orthophosphoric acid because this reactant
is more convenient in handling. Besides, we also changed
the procedure used for the isolation of product 2: we apꢀ
plied continuous extraction with light petroleum using
a Soxhlet extractor.
Dehydrogenation of 2 leading to triphenylene 1 was
also effected according to a modified procedure:22
the reaction was carried out under argon with the prepꢀ
aration of sublimed triphenylene in 99% yield, which
Triphenylene (1). A. Dodecahydrotriphenylene 2 (24 g, 0.1 mol)
and 10% palladium/Sibunite (4 g) were heated for 10 h at 300 C
under argon over the surface cooled with running water. The

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Russ.Chem.Bull., Int.Ed., Vol. 63, No. 7, July, 2014
Kovalev et al.
sublimed product was mechanically removed from the surface.
The yield was 22.57 g (99%), m.p. 196—198 C. Found (%):
C, 94.56; H, 5.21. C18H12. Calculated (%): C, 94.70; H, 5.30.
1H NMR, : 7.66 (m, 6 H); 8.66 (m, 6 H). 13C NMR, : 123.33,
127.23, 129.85. MS (EI), m/z (%): 228 [M]+ (100).
9. T. Yatabe, M. A. Harbison, J. D. Brand, M. Wagner,
K. Müllen, P. Samori, J. P. Rabe, J. Mater. Chem., 2000,
10, 1519.
10. R. Nandy, S. Sankararaman, Org. Biomol. Chem., 2010,
8, 2260.
B. The synthesis was carried out similarly, using 10% Pd/C
and using no argon. The yield of triphenylene was 80%.
11. M. J. Tanga, R. F. Davis, E. J. Reist, J. Heterocycl. Chem.,
1987, 24, 39.
12. L. Verbit, E. Berliner, J. Am. Chem. Soc., 1964, 86, 3307.
13. D. N. Reinhoudt, F. J. Steemers, W. Verboom, E. B. van der
Tol, J. W. Verhoeven, J. Am. Chem. Soc., 1995, 117, 9408.
14. G. W. Gribble, R. B. Perni, J. Org. Chem., 1985, 50, 2934.
15. D. Pena, A. Cobas, D. Pérez, E. Guitian, Sythesis,
2002, 1454.
16. C. Xie, L. Liu, Y. Zhang, P. Xu, Org. Lett., 2008, 10, 2393.
17. M. Fossatelli, L. Brandsma, Synthesis, 1992, 756.
18. I. Nagao, M. Shimizu, T. Hiyama, Angew. Chem., Int. Ed.,
2009, 48, 7573.
This work was financially supported by the Ministry
of Education and Science of the Russian Federation
(State Contract No. 14.A18.21.0817), the Council on
Grants at the President of the Russian Federation (Proꢀ
gram of State Support for Young ScientistsꢀCandidates of
Science (Grant MKꢀ1511.2013.3), and the Government
of the Russian Federation (Program 211, Agreement
No. 02.A03.21.0006).
19. Z. Zhou, T. Yamamoto, J. Organomet. Chem., 1991, 414, 119.
20. C. S. Chao, C. H. Cheng, C. T. Chang, J. Org. Chem., 1983,
48, 4904.
References
21. K. B. Sukumaran, R. G. Harley, J. Org. Chem., 1981,
46, 2740.
22. L. H. Klemm, E. Hall, L. Cousins, C. E. Klopfenstein,
J. Heterocycl. Chem., 1987, 24, 1749.
23. L. H. Klemm, D. Reed, L. A. Miller, B. T. Ho, J. Org.
Chem., 1959, 24, 1468.
24. M. Davoodi, H. R. Safaei, M. Shekouhy, Synth. Commun.,
2013, 43, 2178.
1. Pat. Appl. US 20130001521 A1; http://appft.uspto.gov/
netahtml/PTO/srchnum.html.
2. S. K. Pal, S. Setia, B.S. Avinash, S. Kumar, Liq. Cryst., 2013,
40, 1769.
3. R. J. Bushby, K. J. Donovan, T. Kreouzis, O. R. Lozman,
OptoꢀElectron. Rev., 2005, 13, 269.
4. V. Bhalla, H. Singh, M. Kumar, S. K. Prasad, Langmuir,
2011, 27, 15275.
5. Pat. RF 2485084, Byul. Isobret. [Invention Bull.], 2013, No. 17
(in Russian).
6. Pat. WO 2012/86366; http://patentscope.wipo.int/search/
en/detail.jsf.
25. X. Jing, J. Wang, L. Wang, F. Xu, C. Yan, Q. Zhu, X. Ren,
X. Jing, Synth. Commun., 2005, 35, 3167.
26. H. J. Seebald, W. Schunack, Arch. Pharm., 1974, 307, 161.
7. I. S. Kovalev, D. S. Kopchuk, A. F. Khasanov, G. V. Zyryꢀ
anov, V. L. Rusinov, O. N. Chupakhin, Mendeleev Comꢀ
mun., 2014, 24, 117.
8. R. Breslow, B. Jain, R. Q. Kluttz, C.ꢀZ. Xia, Tetrahedron,
1982, 38, 863.
Received February 17, 2014;
in revised form June 6, 2014