Химия и химические технологии / 6

Химия и химические технологии / 6.Органическая химия.

M. Yu. Chernyak, A. A. Morozov, V. E. Tarabanko

Institute of Chemistry and Chemical Technology, Siberian Branch of RAS

Akademgorodok Str., 50/24, Krasnoyarsk, 660036, Russia.

ANTIBACTERIAL ACTIVITY OF
5-HALOMETHYLFURFURAL SEMICARBAZONES

5-Halomethylfurfurals are high-reactive compounds and can be used both to insert furoic cycle in complex molecules and to synthesize various 2,5-substituted furan derivatives [1]. 5-Hydroxymethylfurfural (5-HMF), 5-chloro- and 5-bromomethylfurfurals (5-CMF and 5-BMF respectively) can be synthesized from hexoses with acceptable yields [2-4]. In medical practice, comparatively low number of antibacterials including furoic cycle are applied. Among these compounds, derivatives of 5-nitrofuroic series are a special group.

5-Nitrofurans have a wide range of antibacterial activity, they are effective versus gram-positive and gram-negative, aerobic and anaerobic bacteria [5]. Synthesis of 5-hydroxy- and 5-halomethylfurfurals semicarbazones, the structural analogs of 5-nitrofuroic series, is of interest.

Fig. 1. General formula of antibacterials of 5-nitrofuroic family (on the left side), and 5-HMF, 5-BMF, 5-CMF semicarbazones (on the right side), X: -OH, -Br, -Cl.

The purpose of this report is to synthesize semicarbazones of 5-hydroxy-, 5-chloro-, 5-bromomethylfurfurals and to study their biological activity.

Experimental

Semicarbazones synthesis.

5-HMF, 5-BMF and 5-CMF were synthesized according to techniques [4, 6]. 50 cm³ of aldehyde (0.1 mole) solution in ethanol was added (dropwise with stirring) to water solution containing semicarbazide hydrochloride (11,15 g, 0,1 mole) and sodium acetate (20 g). With low heating, mixture was stirring for 1 hour, and then it was cooled to +4 ^oC. Residue formed was filtered and recrystallized.

NMR spectra were recorded with a Bruker Avance III 600 MHz spectrometer (Centre for Collective Use, Krasnoyarsk Scientific Centre SB RAS) with reference to signal from the deuterated solvent, CDCl₃.

Antibacterial activity research.

Test-microorganisms sensitivity detection (S. Aureus ATCC 25923, E. Coli ATCC 25922 and P. Aeruginosa ATCC 27853) was carried out by serial dilution method to determine minimal inhibitory concentration (MIC) at Federal Budgetary Institution of Health Care “Center of Hygiene and Epidemiology in Krasnoyarsk Territory” for 5-CMF semicarbazone and comparison sample (furacilin).

Results and Discussion

Obtained 5-HMF, 5-CMF, and 5-BMF semicarbazones were not described in literature. They are amorphous powders of cream colour (5-HMF semicarbazone) or pale yellow colour (5-CMF and 5-BMF semicarbazones). NMR spectra of product obtained are presented below.

5-HMF semicarbazone:

¹H NMR (600 MHz, D₂O). δ, ppm: 4,52 (с 1H, -CH₂-ОН), 6,41 (d 1H, CH_fur,), 6,65 (d 1H, CH_fur), 7,68 (s 1H, -СH=N).

5-CMF semicarbazone:

¹H NMR (600 MHz, D₂O). δ, ppm: 4,45 (с 1H, -CH₂-ОН), 6,35 (d 1H, CH_fur,), 6,58 (d 1H, CH_fur), 7,59 (s 1H, -СH=N).

5-BMF semicarbazone:

¹H NMR (600 MHz, D₂O). δ, ppm: 4,34 (с 1H, -CH₂-ОН), 6,46 (d 1H, CH_fur,), 6,70 (d 1H, CH_fur), 7,72 (s 1H, -СH=N).

Bacterial strain choice was made in terms of available literary data on 5-nitrofuroic series medicals efficiency [7]. MIC determination results for 5-CMF and comparison sample are presented in table 1.

Table 1. Minimal inhibitory concentration (MIC, mg/l) of 5-cloromethylfurfural as related to various bacteria.

	S. Aureus ATCC 25923	E. Coli ATCC 25922	P. Aeruginosa ATCC 27853
Furacilin	0,025	0,05	>0,20
5-Cloromethylfurfural semicarbazone	>0,20	>0,20	0,20

Minimal inhibitory concentration value of 5-chloromethylfurfural semicarbazone exceed this one of furacilin as related to P. Aeruginosa. It confirms antibacterial properties of the compound sinthesized.

Referenses

1. Sanda, K. Synthese du 5-bromomethyl- et du 5-cloromethyl-2-furannecarboxaldehyde/ K. Sanda, L. Rigal // Carbohydrate Research. – 1989. – Vol. 187, № 187. - P. 15–23.

2. Lichtenthaler, F.W. Towards improving the utility of ketoses as organic raw materials/ F.W. Lichtenthaler // Carbohydrate Research. - 1998. – Vol. 313, № 2. - P. 69 – 89.

3. Tarabanko V.E., Chernyak M.Yu., Smirnova M.A. 5-hydroxymethylfurfural, levulinic acid and their derivatives. Catalysis by sodium hydrosulfate. Chemical industry today, 2007, № 10. P. 13-23. (Тарабанько В.Е., Черняк М.Ю., Смирнова М.А. 5-гидроксиметилфурфурол, левулиновая кислота и их производные из углеводов. Катализ гидросульфатом натрия. Химическая промышленность сегодня, 2007, № 10. 13-23.

4. Тарабанько В.Е., Черняк М.Ю., Смирнова М.А. Способ получения 5-бромметилфурфурола. Патент РФ 2429234, 2011.

B. C. Stoiceva-Radovanovic and B. Lj. Milic. Thermal Decomposition of 5-nitro-2-furaldehyde Semicarbazone. Journal of Thermal Analysis, Vol. 32 (1987) 485-490

5. http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv2p0393.

6. Humedia A. El-Obeid, Elamin I. Elnima and Abdullah A. Al-Badr. Sunthesis and antimicrobial activity of new furan derivatives. Pharmaceutical research. 1985. P 42-43.