Synthesis of Betulin Dibenzoate and Diphthalate

Article abstract of DOI:10.1007/s10600-017-1976-5

Betulin-3,28-dibenzoate and -3,28-diphthalate were synthesized for the first time by reacting betulin with melts of benzoic and phthalic acids at 190–200°C for 5 min.

Full text of DOI:10.1007/s10600-017-1976-5

DOI 10.1007/s10600-017-1976-5
Chemistry of Natural Compounds, Vol. 53, No. 2, March, 2017
SYNTHESIS OF BETULIN DIBENZOATE AND DIPHTHALATE
1,2
1
1,2*
V. A. Levdanskii, A. V. Levdanskii, and B. N. Kuznetsov
Betulin-3,28-dibenzoate and -3,28-diphthalate were synthesized for the first time by reacting betulin with
melts of benzoic and phthalic acids at 190–200°C for 5 min.
Keywords: betulin, benzoic acid, phthalic acid, melt, esterification, betulin-3,28-dibenzoate, betulin-3,28-diphthalate.
Esters of betulin (1) and other lupane triterpenoids containing aliphatic and aromatic acids possess various biological
activities [1–3]. Known methods for preparing betulin esters focus mainly on acylation of 1 by anhydrides or chlorides of the
corresponding acids in Py or 1-methyl-2-pyrrolidinone [1–4]. It was shown in a patent [4] that 1 was acylated by phthalic
anhydride at 70°C in 48 h in the presence of imidazole in 1-methyl-2-pyrrolidinone.
29
20
30
21
19
11
26
25
13
17
15
CH OH
2
CH OR
1
2
a, b
28
9
3
5
7
27
HO
RO
24
23
2a, b
1
R = Bz (a), HOOCC H CO (b)
6
4
a. BzOH, 190–200°C; b. C H (COOH) , 190–200°C
6
4
2
The development of simple and efficient methods for preparing esters of 1 was stimulated by their high biological
activity. Replacing anhydrides and chlorides of organic acids by the corresponding available acids would simplify and reduce
the cost of preparing esters of 1.
The goal of the research was to study esterification of 1 by melts of benzoic and phthalic acids.
Esterification of 1 by propionic acid in the presence of H PO in toluene with removal of the H O released by the
3
4
2
reaction is known to give betulin-3,28-dipropionate [5].
The corresponding betulin esters could not be produced if the reaction of 1 with benzoic or phthalic acid was carried
out in toluene in the presence of H PO . It was found that 1 began to isomerize into allobetulin if the reaction was carried out
3
4
for 6–8 h.
Betulin (1) was esterified by the aromatic acids upon fusion of 1 with benzoic or phthalic acid at 190–200°C to
produce betulin-3,28-dibenzoate (2a) or betulin-3,28-diphthalate (2b).
–1
The IR spectrum of 2a differed from that of 1 by the lack of a broad OH absorption band at 3429 cm and the
–1
13
appearance of a C=O ester absorption band at 1719 cm . The C NMR spectrum of 2a showed resonances for all 44 C
atoms, which agreed with the empirical formula C H O . Two ester resonances were found at 167.1 and 166.4 ppm.
44 58
4
Resonances of C atoms located in the o-, m-, and p-positions relative to the ester were observed at 129.8, 130.3, 128.5, 128.6,
133.0, and 133.8 ppm. Resonances of quaternary C atoms associated with the ester groups appeared at 130.6 and 131.1 ppm.
1) Institute of Chemistry and Chemical Engineering, Siberian Branch, Russian Academy of Sciences, 50-24,
Akademgorodok, Krasnoyarsk, 660036, fax: +7 (391) 249 48 94, e-mail: inm@icct.ru; 2) Siberian Federal University,
79 Svobodnyi Prosp., Krasnoyarsk, 660041. Translated from Khimiya Prirodnykh Soedinenii, No. 2, March–April, 2017,
pp. 263–264. Original article submitted June 9, 2016.
©
310
0009-3130/17/5302-0310 2017 Springer Science+Business Media New York

Other resonances in the spectrum of 2a were close to those of 1. This indicated that the skeleton of 1 was unaffected during the
reaction. The IR and NMR spectra of 2b agreed with those in the literature [3, 6].
Thus, betulin dibenzoate (2a) and diphthalate (2b) were prepared for the first time by heating 1 with benzoic and
phthalic acids at 190–200°C. The structures and compositions of 2a and 2b were established using IR and NMR spectroscopy
and elemental analysis.
EXPERIMENTAL
–1
IR spectra were taken from KBr pellets (3 mg of sample per 300 mg of KBr) in the range 400–4000 cm on a Tensor-27
13
Fourier IR spectrometer (Bruker, Germany). C NMR spectra were recorded in CDCl (TMS = 0) on a Bruker Avance III
3
TM
spectrometer (600 MHz). Elemental analyses were performed on a Flash EA
1112 elemental analyzer (Thermo Quest,
Italy). The amounts (%) of C, H, and O were determined simultaneously. Analytical data for 2a and 2b agreed with those
calculated.
Melting points were measured on an Electrothermal A9100 apparatus. TLC used Silufol plates (Chemapol, Czech
Rep.) and solvent system CHCl –MeOH (20:1) with detection by phosphotungstic acid solution (20%) in EtOH followed by
3
heating at 100–200°C for 2–3 min and by I vapor. Betulin was prepared by the literature method [7].
2
3ꢀ,28-Dibenzoxylup-20(29)-ene (2a). A 50-mL three-necked flask equipped with a stirrer, thermometer, and reflux
condenser was charged with 1 (4.42 g, 0.01 mol) and benzoic acid (3.66 g, 0.03 mol). The mixture was stirred on an oil bath
at 190–200°C for 5 min, cooled, treated with EtOH (60 mL), filtered hot, and transferred to a beaker for crystallization. Yield
–1
of 2a, 89%, mp 139–140°C. C H O . IR spectrum (KBr, ꢁ, cm ): 3069, 2939, 2868, 1719, 1642, 1603, 1452, 1316, 1272,
44 58
13
4
1176, 1111, 1070, 1027, 711. C NMR spectrum (CDCl , ꢂ, ppm): 38.9 (C-1), 24.2 (C-2), 81.7 (C-3), 38.4 (C-4), 55.5 (C-5),
3
18.3 (C-6), 34.3 (C-7), 41.1 (C-8), 50.4 (C-9), 36.6 (C-10), 20.8 (C-11), 25.4 (C-12), 37.8 (C-13), 42.8 (C-14), 27.2 (C-15), 30.0
(C-16), 46.9 (C-17), 49.0 (C-18), 47.8 (C-19), 150.3 (C-20), 29.9 (C-21), 34.9 (C-22), 28.0 (C-23), 16.7 (C-24), 16.1 (C-25),
15.5 (C-26), 14.8 (C-27), 63.4 (C-28), 110.1 (C-29), 19.2 (C-30), 167.1, 166.4 (O–C=O), 130.6, 131.1, 129.8, 130.3, 128.5,
128.6, 133.0, 133.8 (C H ).
6
5
3,28-Diphthaloxylup-20(29)-ene (2b) was synthesized analogously to 2a, yield 87%, mp 168–170°C
(lit. mp 173–175°C [6]). C H O .
46 58
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ACKNOWLEDGMENT
The work was supported financially by the Ministry of Education of Russia (Project RFMEF160714X0031).
Instruments at the Krasnoyarsk Regional Center for Collective Use, SB, RAS, were used.
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