DOI 10.1007/s10600-020-03025-y
Chemistry of Natural Compounds, Vol. 56, No. 2, March, 2020
ONE-POT WITTIG SYNTHESIS OF
METHYL-3-[5-(HYDROXYMETHYL)-2-FURYL]ACRYLATE
FROM FRUCTOSE
*
I. M. Sakhautdinov, R. N. Malikova,
G. F. Sakhautdinova, and A. G. Mustafin
Exhaustion of nonrenewable natural resources has necessitated the development of alternative methods for processing
renewable raw material sources. Carbohydrates represent a large part of yearly renewable biomass and are highly promising
for such processing [1]. Furan compounds are especially interesting because they have many applications in the chemical
industry [2–7]. The plant-derived furan 5-hydroxymethylfurfurol (1, 5-HMF) is being extensively used as a transformation
platform. However, 5-HMF is labile [8] and requires certain storage conditions. Therefore, synthesis of stable 5-HMF derivatives
directly from carbohydrates is a challenging problem for contemporary chemistry.
5-HMF was synthesized by refluxing fructose in DMSO for 2 h followed by a Wittig reaction with
methyl(triphenylphosphoranylidene)acetate (Scheme 1). The latter reaction occurred at room temperature in 1 h. Flash
chromatography over silica gel isolated two products 2a and 2b in a 4:1 ratio.
O
O
3
a
b
5
1'
HO
HO
O
HO
Fructose
O
+
O
O
O
1''
3'
1
O
1
c
2b
2a
a. DMSO, 150°C; b. Ph =CHCOOMe; c. 1. DMSO, 150°C; 2. Ph P=CHCOOMe
3
3
Scheme 1
The structures of 2a and 2b, which were isolated pure, were elucidated using physicochemical analytical methods.
13
The main indicators were disappearance of the 5-HMF aldehyde, which appeared in C NMR spectra at 178.56 ppm, and
formation of a multiple bond with resonances at 115.37 and 115.76 ppm in 2a and at 114.09 and 118.04 ppm in 2b.
Olefination of 5-HMF without isolation from DMSO gave analogous results. The best yield (56%) from both
approaches was observed with a slight (1.2×) excess of the phosphorane calculated for starting fructose.
Thus, a one-pot synthesis of a stable 5-HMF derivative (platform compound) with good water-solubility was developed
and made it highly promising for biological screening.
Preparation of 2a and 2b. Crystalline fructose (Sladis, 0.5 g, 2.8 mmol; natural fruit sugar, OOO Arkom) was
dissolved in DMSO (2.5 mL) and heated at 150°C with constant stirring on an oil bath for 2 h (the yield was 67% if 5-HMF
was isolated). The reaction mixture was cooled to room temperature, treated with methyl(triphenylphosphoranylidene)acetate,
and stored for 1 h at room temperature. The products were isolated by column chromatography over silica gel using petroleum
ether–EtOAc (7:3).
1
Methyl (2E)-3-[5-(Hydroxymethyl)-2-furyl]acrylate (2a). Powdery light-brown compound, mp 50°Ñ. Í NMR
spectrum (CDCl , δ, ppm, J/Hz): 7.38 (1Í, d, J = 15.8, H-2′), 6.54 (1Í, d, J = 3.3, H-3), 6.36 (1Í, d, J = 3.3, H-4), 6.28 (1Í,
3
13
d, J = 15.8, H-3′), 4.62 (2Í, s, H-1′′), 3.78 (3Í, s, OCH ), 2.19 (1Í, br.s, OH). C NMR spectrum (CDCl , δ, ppm): 51.70
3
3
(ÑH ), 57.58 (ÑH ), 110.19 (=ÑH), 115.37 (=ÑH), 115.76 (=ÑH), 131.11 (=ÑH), 150.72 (=Ñ), 156.62 (=Ñ), 167.58 (O=Ñ).
3
2
Found, %: Ñ 59.39; H 5.58. C H O Calcd, %: Ñ 59.34; H 5.53; O 35.13.
9
10 4.
Ufa Institute of Chemistry, Russian Academy of Sciences, 69 Prosp. Oktyabrya, Ufa, Republic of Bashkortostan,
450054 Russia, e-mail: ioh039@mail.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 2, March–April, 2020,
pp. 294–295. Original article submitted August 29, 2019.
©
0009-3130/20/5602-0341 2020 Springer Science+Business Media, LLC
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