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8Journal of Siberian Federal University. Chemistry 1 (2015 8) 19-24
УДК 544.147:678.044.55
Formation of 5-Fluoromethylfurfural from 5-Halomethylfurfurals Catalyzed by Crown Ethers
Mikhail Yu. Chernyaka, Valery E. Tarabankoab*, Andrey A. Morozova and Alexander A. Kondrasenkoa
aInstitute of Chemistry and Chemical Technology SB RAS 50/24 Akademgorodok, Krasnoyarsk, 660036, Russia
bSiberian Federal University 79 Svobodny, Krasnoyarsk, 660041, Russia
Received 28.12.2014, received in revised form 16.02.2015, accepted 03.03.2015
5-fluoromethylfurfural has been obtained by interaction of 5-bromo- and 5-chloromethylfurfurals with potassium bifluoride in the presence of dibenzo-24-crown-8 and 18-crown-6 in acetonitrile medium. The yield attains 40-60 mol. %, and the selectivity of 5-bromomethylfurfural conversion is close to 90 %. The NMR and MS spectra are described. The results demonstrate the capability of the KHF2/ crown-ethers system to process biomass-derived feedstock molecules to valuable furan compounds by exchange reactions.
Keywords: 5-fluoromethylfurfural, 5-bromomethylfurfrural, 5-chloromethylfurfrural, 18-crown-6, dibenzo-24-crown-8.
© Siberian Federal University. All rights reserved
* Corresponding author E-mail address: [email protected]
Получение 5-фторметилфурфурола из 5-галогенметилфурфуролов в присутствии краун-эфиров
М.Ю. Черняка, В.Е. Тарабанькоаб, А.А. Морозов3, А.А. Кондрасенкоа
аИнститут химии и химической технологии СО РАН Россия, 660036, Красноярск, Академгородок, 50/24 бСибирский федеральный университет Россия, 660041, Красноярск, пр. Свободный, 79
Изучен селективный процесс получения 5-фторметилфурфурола путем взаимодействия 5-бром и 5-хлорметилфурфуролов с гидрофторидом калия в присутствии дибензо-24-каун-8 и 18-краун-6 эфиров в среде ацетонитрила. Выход продукта реакции достигает 40-60 мол. %. Приведены ЯМР 1Н и масс-спектр продукта. Полученные результаты демонстрируют возможность применения системы KHF2/краун-эфир для получения высокореакционных фурановых соединений из возобновляемого сырья.
Ключевые слова: 5-фторметилфурфурол, 5-бромметилфурфурол, 5-хлорметилфурфурол, 18-краун-6, дибензо-24-краун-8.
Introduction
Carbohydrates are the only and practically unlimited source of furan compounds, such as 5-hydroxymethylfurfural (5-HMF), 5-chloro- and 5-bromomethylfurfural (5-CMF and 5-BMF). Fluoro-derivatives of furan compounds may have biologic activity [1-3], and therefore synthesis of such compounds is of great interest. 5-trifluoromethylfurfural was synthesised by interaction of furfural with trifluoroacetic acid and xenon difluoride [1]. 5-fluoromethylfurfural (5-FMF) might be commercially available [4], but promising synthetic methods for its production are not described in literature. Predicted properties of 5-FMF are generated using the ACD/Labs' ACD/PhysChem Suite and presented in [5].
Low nucleophility of fluoride ion along with low solubility of 5-halomethylfurfurals (5-HalMF) do not allow to obtain acceptable yield of 5-FMF by ion exchange between silver fluoride and 5-HalMF in water. The highest yields for this exchange reaction (5-10 mol. %) were observed in the 5-BMF -toluene - silver fluoride heterogeneous system [6]. The main products of such process were various isomers from alkylation of toluene by 5-BMF.
In order to increase nucleophilic strength of fluoride ion in fluorination reactions, crown ethers as the mass transfer catalysts are widely used [8, 9, 10]. Despite these advances, such approaches have not been applied to synthesise 5-FMF from 5-HalMF.
The goal of the present paper is to study a formation of 5-FMF by action of potassium bifluoride on 5-HalMF in the presence of crown ethers.
Hexose
0
Hal
800C CH£N
0
F
Hal: Clor Br
crown-ether
Experimental
5-BMF and 5-CMF were syntherised according to [10, 11]. Dibenzo-24-crown-8 and 18-crown-6 from ACROS organics (USA, New Je rsey), KHF2 and acetonitrile from «KCimreaktivsnab» (Russia, Bashkortostan, Ufa) were used inthie sSudy. 2200 neiLL oir acetomtrile was mixed with 5-HalMF (0.01 mol), crown ether (0.005 mol), and potaseium bifluoride (0. f mol). The reaction proceeded for 20-50 hours at 80 °C with conslant itirring to intensify the rnterphfse ion exchange. The substcate consumption and the product accumulaeion wene monitored by gas chromatography (Chromctec Kristall 2000M). After reaction the organic phase wae fietered, evaporated at normal pressirre;, and the resirlue wws distilled under vacuum (l-2 mm Hg). Thepeoduct was identified by GC-MS and NMR. NMR spectra were recorded with a Bruker Avance III 600 MHz spectrometer fCentre for Collective Use, Krasnoyarsk Scientific Centre SB RAS) witli reference to the signaf from she deuteeated solveat. GC-MS study was carried out with an Agilent 7890A unit.
Acetonitrile is a convenient aprotic solvent used for ion exchange reactions mediated by crown ethers [7, 8]. Increasing the crown ether to 5-HalMF molar ratio from 1:8 to 1:5 had almost no effect on the reaction rate. The reaction is highly selective, and 5-FMF is the only detectable product. The dependence graph of the substrate and the product concentrations versus reaction time is presented in Fig. 1.
After approx. 35 hours of reaction a half of the substrate is transformed; after this 5-FMF stops accumulating while concentration of 5-BMF continues to decline. The maximum product yield attains 0,8 g (42 mol. %).
Fig. 1. Dependence of 5-fluoromethylfurfural concentrations versus time. 80 °C, 0.01 M dibenzo-24-crown-8. (1) - 5-bromomethylfurfural (initial concentration 0.052 M); (2) - 5-fluoromethylfurfural; (3) - the sum of 5-BMF and 5-FMF concentrations
Results and discussion
0,000
0 5 10 15 20 25 30 35 40 45
Time, h
The data on reactivity of 18-crown-6 in the same process under the similar conditions are shown in Fig. 2, and a rate of the process estimated by the substrate half-life is of seven times more as compared with dibenzo-24-crown-8 catalyzed process (Fig. 1). 18-crown-6 functions as a ligand for some metal cations with a particular affinity for potassium cations, and this affinity causes high rate of the process. Maximum analytic yield of 5-FMF obtained in the process catalyzed by 18-crown-6 attains value of 60 mol. %.
5-CMF is less reactive as a substrate for the 5-FMF synthesis. Fig.ure 3 shows the kinetics of consumption of 5-CMF and formation of 5-FMF. The 5-CMF half-life is of appr. 20 hours, and the product analytic yield does not exceed 40 mol. %.
0.050 -,
0.045
0.040
^ 0.035
c 0.030 o
'ro 0.025 | 0.020 § 0.015 ° 0.010 0.005 0.000
3 ▲
8 10 Time, h
12 14 16 18
Fig. 2. Dependence of 5-fluoromethylfurfural concentrations versus time. 80 °C, 0.01 M 18-crown-6 concentration. (1) - 5-bromomethylfurfural (initial concentration 0.05 MM)); (2) - 5-fluoromethylfurfural; (3) - the sum of 5-BMF and 5-FMF concentrations
0.060-,
0.055-
0.050-
0.045-
0.040-
c 0.035-
o
to 0.030-
"c 0.025-
e
o c 0.020-
o o 0.015-
0.010-
0.005-
0.000-
10 15 Time, h
20
25
Fig. 3. Time dependence of 5-chloromethylfurfural into 5-fluoromethylfurfural conversion. 80 °C, 0.01 M 18-crown-6 concentration. (1) -5-chloromethylfurfural ((initial concentration0.05 M); (2) - 5-fluoromethylfurfural; (3) - the sum of 5-CMF and 5-FMF concentrations
3
0
5
The spectral data for 5-fluoromethylfurfuraL
'H NMR spectral data (600 MHz, CDCy. 5, ppm: 5.4 (d 2H, -CH2-, J2h-f = 48 Hz), 6.7 (d/d 1H,
CHfur, J23H-f = 1.38 Hz, J23H-4H = 3.60 Hz), 7.3 (d/d 1H, CHfur, J24H-F = 1.338 Hz, J23H-4H = 3.54 Hz), 9.7 (s 1H, CHO).
13C NMR spectral data (600 MHz, CD Cl3). 5, ppm : 178.2 (s Cf, 154. 5 (d C5, J2C-F = 18.5 Hz), 14-8 (s C2), 121.5 (s C3), 113.2 (d C4, J2c-f = 6 Hz), 75.5 (d C6, J2c-f = 166.2 Hz-).
The observed spin-spin coupling constant for fluoromethyl group J2H-F = 48 Hz is in agreement with the typical values for this group [12, 13].
Mass-spectrum, 70 eV, m/z (rel. int.): 1)289 [M( (100), 127[M-H[ (75), 110[M-F]+ (3), 99) [M-CHOJ+ (35), 81 [M-CHO-F] (3), 80 (3), 71 (45), 70 (26), 69(23), 53(15), 52[20), 551 (100), 5n50), 49(10).
Chemical properties. B.p. 98 0C (0.2 mm Hg). The substance is stable in solutions of 1:1 wateo-acetonitrile at 60 oC during one hours, and with 0.01 M of HCl or NaOH additives in the same solution at 25 °C during 5 hours. On the other hand, the subctance may spontaneously resinify when storing even in a refrigerator at -5 ^ -10 oC durind a week. Purification of crude 5-FMF by vacuum distillation was also complicated by its resinification. Such a behavior of the compound makes questionable the possibility of its commercial production [14, 15]. Instability of the compound may be ascribed to autocatalytic origin of resinification by HF in non-aqueous media. Nevertheless, 40 and more mol. % preparative yields of the product were attained.
The obtained results show that 5-fluoromethylfurfural can be obtained with a good yield attained 40-60 mol. % by interaction of 5-chloro- and 5-bromomethylfurfural with potassium bifluoride catalyzed by 18-crown-6 in acetonitrile medium, but the problem of its stability requires to be solved.
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7. Hiraoka M. Crown Compounds. Their Characteristics and Applications, Elsevier Scientific Publishing Company, New York, 1982.
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4
References
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