CS264706B1 - Silanizing agent for the preparation of non-polar bound phases for chromatography and a method for its preparation - Google Patents

Abstract

The subject of the solution is a silanizing agent for the preparation of non-polar bonded phases for chromatography of the general formula I, CH, i -> R-Si-Cl (I) I ch3 where R represents a linear unbranched alkyl C^g and C^g, which is a mixture of two substances in the ratio Clg:C16 - 3:1 to 1:3, and a method of its preparation by the Grignard reaction from dimethyldichlorosilane and halides R-X, where X - Cl, Br, J, prepared from alcohols obtained by reduction of esters of the corresponding fatty acids, obtained from natural sources.

Description

(57) The object of the solution is a silanizing agent for the preparation of non-polar bound phases for chromatography of the general formula I,

CH, i ->

R-Si-Cl

I CH ₃ wherein R is a linear branched alkyl, C ^ g C ^ g, which is a mixture of two compounds in the ratio of C _g C _16-3: 1 to 1: 3, and a process for the preparation of the Grignard reaction of dimethyldichlorosilane and the halide RX wherein X - Cl, Br, J, prepared from alcohols obtained by reducing the esters of the respective fatty acids obtained from natural sources.

CS 264 706 Bl

SUMMARY OF THE INVENTION The present invention provides a silanizing agent for preparing non-polar bound phases for chromatography of Formula I

CH,

I ³

R-Si-C (I), wherein R is linear alkyl, branched C _{g g} 'C, which is a mixture of two substances ^{C 18: C} 16 ° ^{in the} right ^{RAERO 3: 1 to 1: 3, and} the preparation of the spĎsob mixtures of the relevant fatty acids obtained from natural sources and a process for the production thereof.

Silica gels with the chemically bonded aliphatic group n-octadecyl are the most commonly used column packings for chromatography. These materials are prepared by reacting silanizing agents with free silanol groups on the surface of silica gel sorbents. The reactive groups of the silanes X are most often ethoxy groups or chlorine or amino groups and are thus: XSi (Y) ₂ -n-octadecyl. The groups Y are e.g. methyls but also other reactive groups X. The first case, ie dimethyloctadecylsilanes, is preferable because the hydrolysis of the remaining X groups results in additional polar silanol groups which, on the one hand, interfere with the use of sorbent in the actual separation and on the other hand parasitic subsequent silanization reactions.

The preparation of silanizing agents is based on conventional chemical reactions described in the literature e.g. Helv. Chim. Acta. 59, 717-727 (1979) and the corresponding silanizing agents are commonly available from several manufacturers.

The described silanizing agents are very expensive due to the reduced availability of the starting materials, especially 1-octadecene, octadecyl alcohol and the sophisticated synthesis of silanizing agents.

The present invention provides a novel mixed silanizing agent for the preparation of non-polar bound phases for chromatography consisting of a mixture of compounds of formula I,

CH, ³

R-Si-C

I

CH ₃ wherein R is linear alkyl, branched C ₁₆ and C _g, the two materials are mixed together in the ratio of material with alkyl C ^ g to the substance with a C l _{g of} 3: 1 to 1: 3rd In the preparation of the mixed silanization composition starting from the mixture of fatty acids and C ^ _g C | _g , i.e. from a mixture resulting from hydrotreating of some natural raw materials, preferably derived from stearin.

The compounds are prepared by a multi-step synthesis starting from a mixture of carboxylic acids of formula II,

R ₁ COOH (II) wherein R 1 is a linear unbranched alkyl C ₁₅ and C ₁₇ , being a mixture of two substances in a ratio of C ₇ : C _{3g of} 3: 1 to 1: 3, which are preferably obtained from stearin.

The synthesis proceeds according to the scheme:

r ^ cooo - ^ • r ₁ coor ₂ HYDRID HX

-R-OH- =

II -> R-X ·

mg

RMgX

III IV (CH ₃ , ₂ SiCl

CH, R ¹ -Si-C

CH, (I)

The alcohols of formula IV are prepared by reducing the acids of formula II in a large excess of bis- (methoxyethoxy) sodium aluminum hydride.

Esters of formula (III) are prepared from acids of formula (II) by multiplying the excess of alcohol R 1 OH (R 1 is methyl or ethyl) in the presence of concentrated sulfuric acid and an aromatic solvent, preferably toluene.

The conditions for a high reaction yield are the formation of an emulsion of the reaction components by vigorous stirring.

The resulting mixture of esters III is reduced with complex hydrides in an aromatic solvent, preferably a toluene solution of bis- (moetoethoxy) sodium aluminum hydride can be used.

The alcohol mixture IV is converted by the action of SOCl ₂ on the corresponding chlorides (X-Cl), by the action of hydrogen bromide on the bromides (X = Br) or by the action of iodine and red phosphorus on the corresponding iodides (X = J). The corresponding organo-magnesium reagents are prepared from the halogenated derivatives V by treatment with magnesium in an aliphatic ether, which, by treatment with dimethyldichlorosilane, provides a silanizing agent I. As a reaction medium, methyl 1,1-dimethyl ether is preferred which has a higher boiling point hazardous explosive peroxides.

The new mixed silanizing agent thus prepared was used to prepare a nonpolar liquid chromatography sorbent. Binding to silica gel yields a product which, by its separation selectivity, efficiency and stability, fully meets the requirements for reverse phase liquid chromatography. The use of a mixed silanizing agent is very advantageous because of the readily available raw material feedstocks C18 and C18 derived from a natural source e.g. from stearin, without the need for further technically demanding purification and separation.

Further, the invention is illustrated in the examples without being limited thereto.

Example 1 Preparation of esters III kg of stearic acid and palmitic acid (2: 1)

1 of anhydrous methanol

180 g (100 mL) of concentrated sulfuric acid

500 ml toluene

The mixture of acids, methanol, sulfuric acid H ₂ SO 4 and toluene was heated under reflux with vigorous stirring with a mechanical stirrer for 7 hours. The separated ester layer was separated, washed with 5 L aqueous 5% NaHCO 3 solution. The separated methanol was diluted with 5 L of water and the precipitated ester layer was combined with the ester layer. The combined ester layers were washed with 3 L of 30 ° C warm water and distilled in vacuo. 2 900 to 2 960 g of a mixture of palmitic acid and stearic acid methyl esters of 210 to 220 ° C / 1.9 kPa (90 to 93%) are obtained.

When using anhydrous ethanol, 3050 to 3100 g of a mixture of ethyl palmitate and stearic esters of 210-225 [deg.] C./9.9 kPa (90-93%) are obtained.

Example 2

Preparation of alcohols IV

971 g of a mixture of methyl stearate and palmitate 1100 ml of a toluene solution of bis- (methoxyethoxy) sodium aluminum hydroxide (70%)

2000 ml of anhydrous toluene

A concentrated toluene solution of bis- (methoxyethoxy) sodium aluminum hydride is added dropwise to the toluene ester solution at a rate such that the temperature does not exceed 80-90 ° C, after addition of the hydride the temperature is maintained at 85 ° C for 2 hours. stand at room temperature. After completion of the reaction, the reaction mixture was poured into 2.5 L of 20% sulfuric acid H 2 SO 4 and 1.5 kg of ice. After the decomposition was complete, the warm toluene layer was separated and the aqueous solution was extracted 3 times with 1 L of toluene. The toluene extracts are neutralized by washing with 2 L of a 10% NaHCO 3 solution and then with 2 L of water. After distilling off the toluene, 750-760 g are obtained by vacuum distillation with a boiling point of 210-250 ° C / 1.9 kPa (85%).

Example 3

256 g of a mixture of palmitic and stearic acids

687 ml of bis- (methoxyethoxy) sodium aluminum hydride toluene solution (70%)

Reduced acids are added to the hydride solution at a temperature of up to 80 ° C. The mixture was stirred for a further 12 hours. It is then cooled to 40 ° C and poured onto a mixture of 500 g of ice, 500 g of conc. sulfuric acid H 2 SO 4 and 1 L toluene such that the temperature is in the range of 50 to 80 ° C. The hot toluene layer was separated, washed with sodium bicarbonate solution _NaHCO3 and concentrated to give 180 g mixture of alcohols IV.

Example 4

Preparation of bromide

700 g of 48% HBr hydrobromic acid

400 g of a mixture of alcohols

The mixture of alcohols and hydrobromic acid was stirred vigorously at reflux for 12 hours. After the reaction, the reaction mixture was diluted with water, separating the organic layer to remove the unreacted alcohol washed with concentrated sulfuric acid H ₂ SO _4, ClaI water, with sodium bicarbonate solution of NaHCO ^, dried _CaCl2> Vacuum distillation gave 410 g of product boiling point 145-170 ° C / 200 Pa (83%).

Example 5

Preparation of iodide 20 g of red phosphorus 156 g of iodine 312 g of a mixture of alcohols ^{Y 100-442} · ⁶

The iodine was stirred with phosphorus and heated to 100 ° C after reacting with phosphorous iodide PJ, the mixture was cooled and a molten mixture of alcohols was added. After cooling, 1 L of petroleum ether (b.p. 30-60 ° C) was added and unreacted red phosphorus was separated. The petroleum ether solution was purified by flowing through a silica gel column. 360 g of iodides were obtained, m.p. in. 140 DEG-145 DEG C./0.1 mm Hg (80%).

Example 6

Preparation of chloride

500 g alcohol mixture (1.9 M)

652 g (400 ml) thionyl chloride (5.48 M)

Thionyl chloride is added portionwise to a slightly heated mixture of alcohols. After all thionyl chloride has been added, the mixture is heated at reflux for 8 hours. After the reaction, the excess thionyl chloride is distilled off SOC1 ₂ was stripped of the end of the last remains of thionyl chloride under a water pump vacuum. Distillation yielded 376 g of a mixture of chlorides, mp 145-149 ° C / 33.3 Pa (70.6%).

Example 7

Preparation of alkyl dimethylchlorosilane

To 14.6 g of activated magnesium under 100 ml of anhydrous ether, a solution of 198 g of a mixture of bromides V with a bromine content of Br of 24.6% is added over 30 minutes. The mixture was refluxed under nitrogen for 24 hours, then a solution of 258 g of dimethyldichlorosilane in 400 ml of anhydrous ether was added and refluxed for 48 hours. The mixture is filtered, the ether is evaporated and the residue is distilled on a molecular evaporator. 140 g of silanizing agent I are obtained.

Example 8

To 58 g of activated magnesium below 200 ml of anhydrous 1,1-dimethylethyl methyl ether over 1 hour was added a solution of 774 g of a mixture of bromides V in 1,400 ml of 1,1-dimethylethyl methyl ether. The mixture was refluxed for 8 hours, then 1040 g of dimethyldichlorosilane was added and refluxed for a further 12 hours.

It is filtered hot on a pressure filter, after evaporation of 1,1-dimethyl-methyl ether and excess dimethyldichlorosilane the residue is distilled off on a molecular evaporator. 530 g of silanizing agent I are obtained.

Claims (2)

OBJECT OF THE INVENTION 1. A silanizing agent for the preparation of a non-polar bound phase consisting of a mixture of compounds of formula I, R-Si-Cl (I) characterized in that the mixture consists of two compounds of the formula I, wherein R represents a linear unbranched alkyl group C 1 to C 1 g, the two substances being mixed with each other in a ratio of g to a compound of formula I with a Cg of 3: 1 to 1: 3. 2. A process for the preparation of a silanizing agent of the formula I according to item 1 from a mixture of carboxylic acids of the formula II, R ₁ -COOH (II) wherein R 1 is a linear unbranched alkyl of C ₁₅ and C ₁₇ , being a mixture of two substances in a ratio of ^C 15 ^{: C} 17 of ^{3: 1 to 1: 3} obtained from stearin which is a mixture of palmitic acid and stear, characterized in that said mixture of acids is esterified in an emulsion of reaction components and an aromatic solvent, e.g. toluene to a mixture of esters of formula III, R ₁ -coor ₂ (III) wherein R 1 is as defined above and R ₂ is ethyl or methyl, then said esters are reduced with complex hydrides, e.g. bis- (methoxyethoxy) sodium aluminum hydride to the alcohols of formula IV, R-OH (IV) wherein R is as defined in 1. These alcohols are converted to halogen derivatives of formula V, R-X (V) wherein R is as defined above and X is chlorine, bromine or iodine and halogen derivatives with a Grignard reaction with dimethyldichlorosilane of formula VI 2H, R-Si-C I CH, (VI) in an aliphatic ether environment, e.g. Of 1,1-dimethylethyl methyl ether to the object compounds of formula I.