SU1428755A1 - Method of producing n-alkyl-beta-d-glycosides - Google Patents

Abstract

The invention relates to substituted glycoeids, in particular, the process for the preparation of n-octol-B-glucopyranoside or n-dodecyl-D-B-meltoside ionic detergents used in biochemical studies. Synthesis is carried out by gradual addition of 6.-acetobromoscale to the n-octanol mixture. or n-dodecinol and a catalyst (1: 1: 1-4 ratio) with simultaneous removal of azeotropic distillation of the solvent, toluene, formed during the reaction of water using a Soxhlet extractor. Cadmium carbonate is used as a catalyst. This catalyst makes it possible to exclude the preparation, as in the known process, of silver oxide, i.e. to simplify the process while simultaneously increasing the yield of the target product by 15–2.5%, reducing the process time and its fire hazard by 13 times (due to the replacement of diethyl ether with toluene). 1 hp f-ly. (L

Description

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 ate

The invention relates to an improved process for the preparation of n-alkyl-O-glycosides of the general formula

B

SNG OH

Jo

"G

he

where R OH, Rj - n-octyl,

RJ-.i-D-Glc-p, R, is n-dodeldyl, which are non-ionic detergents and can be widely used in various biochemical studies.

The purpose of the invention is to increase the yield of the target product and simplify the process, which is achieved by using cadmium carbonate as a catalyst, toluene as a solvent and carrying out the process as a whole in certain parameters.

Example 1. n-Octyl- / W-B-glu-Copyranoside.

In a two-neck flask with a capacity of 50 ml of Siabenzhntox, a Soxhlet extractor filled with calcined granulated silica gel (7.5 g), a reflux condenser with a chloro-alumina tube, was placed 5.2 g (40 mmol) of n-octanol, 25 ml of dry toluene and 1 72 g (10 mmol) of cadmium carbonate. The reaction mixture is boiled for 15-20 minutes to remove moisture in the starting reagents. Then to the boiling reaction mixture, 4.11 g (10 mmol of t-acetobromglucose) are added in four equal portions in four equal portions (10 mmol "t-acetobromglucose. After adding" (L-acetobromglucose, the reaction mixture is boiled for another 30 minutes, cooled, insoluble cadmium salts are filtered off, the precipitate is poured into chloroform ml, the filtrate is evaporated, a solution obtained from syrup; from 25 ml of absolute methanol, 0.2 ml of 2N methyl acetate is added to the clear light yellow solution of the reaction mixture sodium and leave overnight at room temperature. it is neutralized with KU-2 (H) resin, evaporated in vacuo and 7.10 g of light yellow syrup are obtained. TLC with witnesses on silica gel in the solvent system of benzene-ethyl acetate-methanol 2: 1: 1, followed by spot detection by heating plates about

0

five

0 5

0 s 0 5 "

five

shown with sulfuric acid, show that the reaction mixture contains mainly n-octanol (R, 0.90) and n-octyl-T3-Bg glucopyranoside (R, 0.61). The reaction products are isolated by column chromatography on silica gel L (40-63j, i). The column (6x5 cm) was sintered successively with chloroform (300 ml) and a solvent mixture of chloroform-methanol 10: 1 (1000 ml). Chromatography results in n-octanol (3.34 g) and chromatographic pure. n-octyl -. / -B-glucopyranoside. After freeze drying - white hygroscopic powder. Weight 2.50 t (85%), -30.2 (C1; MeOH).

Spectrum H (250 MHz,, TMS 0): 0.91 (m, 3N, SNe-, I 7.5 Hz), 1.31 (m, YUN, -CHg-), - 1.62 (m, 2H ,) 1.62 (m, 2H, -CHg-CH); 3.26-3.36 (m, 4H,); 3.50-3.96 (m, CH-OH); 4.26 (d, 1H, anomeric proton, I 7.5 Hz).

Found,%: C 57.20, H 9.59. С „Н ,, 0,

Calculated,%: C 57.51; H 9.65.

Example 2. In a two-neck col-, bu (as in example 1), 1.31 g (10 mmol) of n-octanol, 25 ml of dry toluene and 1.72 g (10 mmol) of cadmium carbonate are placed. The reaction mixture is boiled for 20 minutes to remove moisture in the starting reagents. Then, 4.11 g (10 mmol) o-ace-; is added to the boiling reaction mixture evenly over 2 hours in four equal portions; tobromglucose. After the addition of 5-acetobromoglucose, the reaction mixture is boiled for another 30 minutes and then treated as in Example 1. The result is n-octanol (0.27 g) and chromatographically pure n-octyl-A 0-glucopyranoside. Weight after freeze drying is 2.15 g (70%).

Example 3. In a two-neck flask (as in Example 1), 1.94 g (15 mmol) of n-octanol, 25 ml of dry toluene and I, 72 g (10 mmol) of cadmium carbonate, are placed. The reaction mixture is boiled for 15-20 minutes to remove moisture in the starting reagents. Then, 4.11 g (10 mmol) of α-acetobromoglucose are added to the boiling reaction mixture, uniformly over 1.5 hours in four equal portions. After adding o-acetobromglucose, the reaction mixture is boiled for another 30 minutes and the pressure is worked up as in Example 1. As a result,

n-octanol (0.41 g) and chromatographically pure n-octyl-B-glucopyranoside are prepared. Weight after freeze drying 2.41 g (82%).

Example 4. n-Dodecyl-y5-B- -altose.

In a two-neck flask (as in Example 1), 2.98 g (16 mmol) of n-dodecanol, 25 ml of dry toluene and 0.70 g (4 mmol) of cadmium carbonate are placed. The reaction mixture is boiled for 20 minutes. Then, to the boiling reaction mixture, 2.80 g of the reaction mixture is uniformly added in equal parts for 1.5 hours in 2.80 g. The reaction mixture is boiled for another 20 minutes (4 mmol) of ut-acetobromo maltose. After that, the reaction mixture is boiled for another 20 minutes, cooled, the insoluble cadmium salts are filtered off, the precipitate is washed with 20 chloroform 2x20 ml, the filtrate is evaporated, nojriy4eHHbu syrup is processed and then, as in the case of the addition of ei-acetobrommaltose. dissolved in 20 ml of absolute methanol, 0.2 ml of 2N is added to the resulting clear, light yellow solution. dilute with sodium methoxide and leave overnight at room temperature. The reaction mixture was neutralized with KU-2 (N) resin, methanol was evaporated in vacuo, and 4.60 g of light yellow syrup was obtained; those with witnesses on silica gel in the solvent system of benzene-chloroform-methanol 2: 1: 1 followed by the detection of spots , as in Example 1, indicates that the reaction mixture contains mainly n-dodecanol (R 0.95) and n-dodectane-D-B-maltoside (Rr 0.47). The reaction products are isolated by column chromatography on silica gel L (40-60 d). The reaction time was 13 times and the column (cm) was eluted with a sequence of high flammability, due to chloroform (400 ml) and a 10: 1 mixture of chloroform-methanol ether mixed with chloroform. (1000 ml). As a result of chromatography, n-dodecanol (2.16 g) and chromo 5 DUet are obtained from the PMR spectra. The magnitude of the matographically pure n-dodecyl-xA B-KCSV anomeric protons in the spectra,

Found, 7 ,: С 56,10; H 8.90.

Calculated,%: With 56.46; H 9.08.

Example 5. In a two-neck flask (as in Example 1), 0.74 g (4 mmol) of n-dodecanol, 25 ml of dry toluene and 0.70 g (4 mmol) of cadmium carbonate are placed. The reaction mixture is boiled for 20 minutes. Then, in a boiling reaction mixture, 2.80 g (4 mmol) o (-acetobromo maltose) are added evenly in four equal portions over 1.5 hours. After the addition of ei-acetobromomaltose

re 4. Chromatography yields n-dodecanol (0.47 g) and chromatographically pure n-do-b-B-maltoside. Weight after freeze drying .1.22 g (60%) ..

The use of carbonate as KaTajm3aTopa eliminates the separate stage of the preparation of freshly prepared silver oxide and, therefore, simplifies the process of obtaining n-alksh1-B-glycosides. The gradual addition of 1-acetobromoscale to the alcohol-catalyst mixture makes it possible to create a large excess of alcohol at the initial stages of the process, which, combined with the use of cadmium carbonate as a catalyst, results in a substantial (by 15-25%) increase in the yield of the target glycosides. Carrying out the process in boiling toluene makes it possible to efficiently remove water from the reaction mixture by azeotropic distillation of the solvent, reducing the build-up of the compounds obtained after

The reaction mixture is boiled for another 20 minutes and then treated, as in the example of the reaction, 13 times and eliminates the high fire hazard associated with the use of diethyl ether. COMES from the data of the PMR spectra. ESS values of anomeric protons in spectra,

Found, 7 ,: С 56,10; H 8.90.

Calculated,%: With 56.46; H 9.08.

Example 5. In a two-neck flask (as in Example 1), 0.74 g (4 mmol) of n-dodecanol, 25 ml of dry toluene and 0.70 g (4 mmol) of cadmium carbonate are placed. The reaction mixture is boiled for 20 minutes. Then, in a boiling reaction mixture, 2.80 g (4 mmol) o (-acetobromo maltose) are added evenly in four equal portions over 1.5 hours. After the addition of ei-acetobromomaltose

The reaction mixture is boiled for another 20 minutes and then treated, as in the example of the reaction, 13 times and eliminates the high fire hazard associated with the use of diethyl ether. COMES from the data of the PMR spectra. ESS values of anomeric protons in spectra,

re 4. Chromatography yields n-dodecanol (0.47 g) and chromatographically pure n-do-b-B-maltoside. Weight after freeze drying .1.22 g (60%) ..

The use of carbonate as KaTajm3aTopa eliminates the separate stage of the preparation of freshly prepared silver oxide and, obviously, simplifies the process of obtaining n-alc1-B glycosides. The gradual addition of 1-acetobromoscale to the alcohol-catalyst mixture makes it possible to create a large excess of alcohol at the initial stages of the process, which, combined with the use of cadmium carbonate as a catalyst, results in a substantial (by 15-25%) increase in the yield of the target glycosides . Conducting the process in boiling toluene allows efficient removal of water from the reaction mixture by azeotropic distillation of the solvent, shortens the time

The mixture is boiled for another 20 minutes, and it is processed 13 times and the fire risk is high due to the use of diethyl gas. t from the data of the PMR spectra. The magnitudes of the anomeric protons in the spectra,

The structure of the compounds obtained after

- maltozid. After freeze drying, a white hygroscopic powder. Weight 1.51 g (74%). G, (+45.5 (C1, MeOH).:

Spectrum n (250 MHz,,): 0.90 (t, 3N, I 8.0 Hz), 1.30 (m, 18H, -SHg-); 1.63 (m, 2H-); 3.20-3.38 (m, bH-CHAOH), 3.41-3.96 (m, 8H, CH-OH); 4.29 (d, 1H, anomeric proton, I 7.8 Hz), 5.18 (d, 1H, anomeric proton, I 3.5 Hz).

0

five

n-octyl-y B-glucoside I 7.5 Hz (example 1) and n-dodecyl- / 3-B-maltoside I 7.8 Hz (example 4) yk: call on / 3-B- the glycosidic bond configuration of these compounds. The purity of the obtained glycosides is confirmed by PMR spectroscopy, thin layer chromatography, the value of the specific rotation value, and the results of elemental analysis.

According to c-spectroscopy data (Bru-cker HX-90, TMS O, ppm) in the spectrum of n-octyl-y -B-glucopyranosi

yes, hydrocarbon chain signals are observed at 14.4 (C-8); 23.5; 26.9 g 30.2; ZO, A; 30.6 and 32.8 (signals C-2 to C-7); 62.5 (C-1) and signals of the glucopyranoside ring 70.8 (C-6) 71.4; 74.8, - 77.5; 77.8 (signals C-2 to C-5); 104.0 (C-1). The magnitude of the chemical shift of the signal of the anomeric carbon atom (104.0) indicates the / -configuration of the glycosidic bond. Other signals in the region of 90-110 ppm not observed, indicating the absence of a iii-anomer.

In the spectrum of n-dodecyl- / -D-maltoside, hydrocarbon chain signals 14.4 (C-11), 23.6, 27.0; 30.3; 30,., And 32.9 (signals C-2 to C-10); 62.6 (C-1) and disaccharide part signals 71.0; 73.1; 74.0, 74, 74.9; 76.4; 77.7; 80.9; 102.6 (-C-1); 104.1 (C-1). The magnitude of the chemical shift of the anomeric atom. C-1 (104.1) indicates the configuration of the glycosidic linkage of maltose with n-dodecanol. Signal at 102.6 ppm belongs to the C-1 atom of the second D-glucopyranose ring attached to the first D-GLUCOSE ring (α-glycosidic bond, in the 90-110 ppm region, no other signals are observed, indicating the absence of the p-anomer.

In a sample of n-octyl-B-glucopyranoide, GLC detected an impurity of an unidentified nature with a content of 1%. With regard to the n-dodecyl - - / -B-maltooside method, gah does not provide unambiguous information on the purity of the obtained product.

Claims (2)

Invention Formula . one . The method of obtaining n-apkyl-D- -glycosides of the general formula CHzOH / HE n where is RI R. he, Rj is n-octyl, of-D-Glc-p, Rj is n-dodecyl, by reacting o (acetobromosaccharide with n-alkane in the medium of the organic solvent in the presence of a catalyst, separating inorganic salts, evaporating solvent, saponification of the reaction mass with sodium methoxide and isolation of the target product by column chromatography, due to the fact that, in order to increase the yield of the target product and simplify the process, cadmium carbonate is used in the quality of the catalyst, medium toluene, with the gradual addition of "-acetobr Omsachara to a mixture of n-alkanol and a catalyst with simultaneous removal of the patterns during the reaction of water by azeotropic distillation of the solvent using a Socketlet extractor. 2. The method according to claim 1, characterized by the fact that the process is carried out at a ratio of the reactants in the (aceto-bromo sugar catalyst: n-alkanol 1: 1: 1-4.