JPH0196009A - Method for stabilizing against hydrolysis of aminoalkyl silica by crosslinking together with transforming amino groups into tertiary forms - Google Patents
Method for stabilizing against hydrolysis of aminoalkyl silica by crosslinking together with transforming amino groups into tertiary formsInfo
- Publication number
- JPH0196009A JPH0196009A JP62251685A JP25168587A JPH0196009A JP H0196009 A JPH0196009 A JP H0196009A JP 62251685 A JP62251685 A JP 62251685A JP 25168587 A JP25168587 A JP 25168587A JP H0196009 A JPH0196009 A JP H0196009A
- Authority
- JP
- Japan
- Prior art keywords
- amino groups
- silica
- aminoalkyl
- formula
- tertiary
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 59
- 239000000377 silicon dioxide Substances 0.000 title claims abstract description 31
- -1 aminoalkyl silica Chemical compound 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims description 4
- 230000000087 stabilizing effect Effects 0.000 title claims 2
- 125000003277 amino group Chemical group 0.000 title abstract description 13
- 238000004132 cross linking Methods 0.000 title abstract description 8
- 230000001131 transforming effect Effects 0.000 title abstract 3
- 230000007062 hydrolysis Effects 0.000 title description 16
- 238000006460 hydrolysis reaction Methods 0.000 title description 16
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 3
- 125000003158 alcohol group Chemical group 0.000 claims abstract 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract 2
- 125000004434 sulfur atom Chemical group 0.000 claims abstract 2
- 239000000126 substance Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 15
- 125000004970 halomethyl group Chemical group 0.000 abstract description 5
- 238000012856 packing Methods 0.000 abstract description 5
- 125000001302 tertiary amino group Chemical group 0.000 abstract description 2
- 239000004593 Epoxy Substances 0.000 abstract 1
- 125000005037 alkyl phenyl group Chemical group 0.000 abstract 1
- 125000004103 aminoalkyl group Chemical group 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 125000001033 ether group Chemical group 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 230000003301 hydrolyzing effect Effects 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 3
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 150000001728 carbonyl compounds Chemical class 0.000 description 3
- 150000001805 chlorine compounds Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- ATWLRNODAYAMQS-UHFFFAOYSA-N 1,1-dibromopropane Chemical compound CCC(Br)Br ATWLRNODAYAMQS-UHFFFAOYSA-N 0.000 description 1
- HUYAKTSUCVTVDP-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr.BrCCCBr HUYAKTSUCVTVDP-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- MCLXOMWIZZCOCA-UHFFFAOYSA-N 3-[methoxy(dimethyl)silyl]propan-1-amine Chemical compound CO[Si](C)(C)CCCN MCLXOMWIZZCOCA-UHFFFAOYSA-N 0.000 description 1
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 1
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Silicon Compounds (AREA)
- Silicon Polymers (AREA)
Abstract
Description
【発明の詳細な説明】
[産業上の利用分野] 本発明は液体クロマトグラフィ
ーに使用する分離用カラムの充てん剤の新規な改良方法
に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel method for improving packing materials for separation columns used in liquid chromatography.
[従来の技術] アミノアルキル結合シリカは順相系ク
ロマトグラフィー用のカラム充てん剤であるが、アミノ
基のイオン交換性を利用する移動相系や、糖類の分離の
ように水と有機溶媒の混合移動相系など、極めて広範囲
の分野で利用されている。ところが、水を含有する移動
相、特にpH8以上の移動相を使用すると、アミノアル
キルシリル基が加水分解脱離する結果、それに伴なって
分離能の低下を来す。あるいは又、試料中にカルボニル
化合物、酸アミド、酸塩化物、塩化チオニル、ハロメチ
ル化合物等が存在すると、充てん剤のアミノ基水素と反
応し、対応する置換体に変化する結果、それに伴なって
分離能の変化を来す。このように従来使用されているア
ミノアルキル結合シリカは1級〜2級アミノ基を含んで
いるため充てん剤としての寿命が極めて短く、頻繁に充
てん剤を交換しなければならない欠点があった。[Prior art] Aminoalkyl-bonded silica is a column packing material for normal phase chromatography, but it is also used in mobile phase systems that utilize the ion exchange properties of amino groups, and in mixtures of water and organic solvents such as in the separation of sugars. It is used in a wide range of fields, including mobile phase systems. However, when a mobile phase containing water, particularly a mobile phase with a pH of 8 or higher, is used, the aminoalkylsilyl group is hydrolyzed and eliminated, resulting in a corresponding decrease in separation ability. Alternatively, if a carbonyl compound, acid amide, acid chloride, thionyl chloride, halomethyl compound, etc. is present in the sample, it will react with the amino group hydrogen of the packing material and change to the corresponding substituent, resulting in separation. This brings about a change in Noh. Since the aminoalkyl-bonded silica conventionally used contains primary to secondary amino groups, it has an extremely short life as a filler and has the drawback of requiring frequent replacement of the filler.
[発明が解決しようとする問題点] 1級〜2級アミノ
基はカルボニル化合物、酸無水物、酸塩化物、塩化ヂオ
ニル化合物、ハロメチル化合物等と極めて容易に反応し
て対応する比較的安定な置換体、例えばシッフ塩基、酸
アミド、および3級アミノ化合物等になる。すでに酸塩
化物や酸無水物によるアミノ基のアシル化は行なわれて
いるが、生成物が酸アミドであるため、アミノ基本来の
もつ分離能が得られない等の欠点がある。塩化チオニル
化合物も同様な問題がある。これらに較ベハロメチル化
合物は3級アミノ化合物になるが、アミノ基本来のもつ
分離能はほとんど損なわれず、しかもアミノ基間を架橋
することができ、加水分解に対して極めて安定な結合基
になる。本発明はこの原理を応用したものである。[Problems to be solved by the invention] Primary to secondary amino groups react extremely easily with carbonyl compounds, acid anhydrides, acid chlorides, dionyl chloride compounds, halomethyl compounds, etc., resulting in relatively stable substitutions. compounds such as Schiff bases, acid amides, and tertiary amino compounds. Acylation of amino groups with acid chlorides or acid anhydrides has already been carried out, but since the product is an acid amide, there are drawbacks such as the inability to obtain the separation ability inherent in amino groups. Thionyl chloride compounds have similar problems. Compared to these, the behalomethyl compound is a tertiary amino compound, but the separation ability inherent in the amino base is hardly impaired, and moreover, the amino groups can be crosslinked, making it an extremely stable bonding group against hydrolysis. The present invention applies this principle.
[問題点を解決するための手段] E S r RN
II を又は三5iRN11(C111C111N1
()。〜、。−CIltCIItNIItで示されるア
ミノアルキル結合シリカを、XCIIIR’ 又XCl
1.[l″CIl!Xで示されるハロメチル化合物と反
応し、III IIIIII
1ll−N−C11*−R
’−CII*4−C11t−R’−C1lt−N−′の
ような一般式で表わされる架橋構造のアミノアルキル結
合シリカに改質することによって、従来のようなアミノ
基特有の分離能を損なわずに加水分解安定性を向上する
。[Means for solving problems] E S r RN
II or 35iRN11 (C111C111N1
(). ~,. The aminoalkyl-bonded silica represented by -CIltCIItNIIT can be
1. Reacts with a halomethyl compound represented by [l″CIl!X, III IIIIII
1ll-N-C11*-R
By modifying to aminoalkyl-bonded silica with a crosslinked structure represented by a general formula such as '-CII*4-C11t-R'-C1lt-N-', the conventional separation ability unique to amino groups is impaired. Improves hydrolytic stability without oxidation.
[作用] 本発明は従来の1〜2級アミノアルキル結合
シリカにハロメチル化合物を反応して、アミノ基間が架
橋されたアミノアルキル結合シリカに改質することによ
って、加水分解安定性の良好な充てん剤を調製する方法
である。[Function] The present invention reacts conventional primary to secondary aminoalkyl-bonded silica with a halomethyl compound to modify it into aminoalkyl-bonded silica in which amino groups are crosslinked, thereby creating a filling with good hydrolytic stability. This is a method for preparing a drug.
さらに反応させるハロメチル化合物の選択によりて、分
離特性を変えることもできる。以下にその詳細を説明す
る。Further, the separation characteristics can be changed by selecting the halomethyl compound to be reacted. The details will be explained below.
従来から順相系充てん剤として使用されているアミノプ
ロピル結合シリカ 5i−CIItClltCIItN
IItは、9118以上の含水移動相中で加水分解が起
り、アミノプロピルシリル基を脱離する。これに対し本
発明の3級化架橋アミノプロピル結合シリカは加水分解
安定性が良好なため結合基の脱離が起らない。Aminopropyl-bonded silica 5i-CIItClltCIItN, which has been conventionally used as a normal phase packing material
IIt undergoes hydrolysis in a water-containing mobile phase of 9118 or higher to eliminate the aminopropylsilyl group. In contrast, the tertiary cross-linked aminopropyl-bonded silica of the present invention has good hydrolytic stability, so that the bonding group does not detach.
その例を図1に示す。An example is shown in FIG.
舅中の本発明品は、従来のアミノプロピル結合シリカに
1.3−ジブロモプロパン[ビス(ブロモメチル)メタ
ン]を反応して得た3級化架橋アミノプロピル結合シリ
カであり、明らかに安定である。The product of the present invention, which has been developed by Kashinaka, is a tertiary cross-linked aminopropyl-bonded silica obtained by reacting conventional aminopropyl-bonded silica with 1,3-dibromopropane [bis(bromomethyl)methane], and is clearly stable. .
この例は、それぞれのシリカをフラスコに採り、pH1
0の緩衝液を加え、撹はんしながら50℃に保ち、所定
時間加水分解後フラスコ中のシリカを採取し、よく洗浄
して乾燥し、その窒素含量を常法で測定したものである
。縦軸の窒素保有率は、加水分解前の窒素含有量を10
0として示しである。In this example, each silica was placed in a flask and the pH was adjusted to 1.
0.0 buffer solution was added, the temperature was maintained at 50° C. with stirring, and after hydrolysis for a predetermined period of time, the silica in the flask was collected, thoroughly washed and dried, and its nitrogen content was measured using a conventional method. The nitrogen retention rate on the vertical axis is the nitrogen content before hydrolysis.
It is shown as 0.
又、加水分解60分後のシリカを洗浄後乾燥し、150
x4.6mmのステンレスカラムに充てんし、アセトニ
トリルと水の混合溶媒を移動相として単糖類を分離した
クロマトグラムの例を図2と図3にそれぞれ示す。これ
でも明らかなように、本発明品の分離能は良好であるの
に対し、従来品は未処理のものに較べ加水分解後の分離
能も低下していることがわかる。In addition, after 60 minutes of hydrolysis, the silica was washed and dried, and
Examples of chromatograms in which monosaccharides were separated using a mixed solvent of acetonitrile and water as a mobile phase packed in a x4.6 mm stainless steel column are shown in FIGS. 2 and 3, respectively. As is clear from this, the separation ability of the product of the present invention is good, whereas the separation ability of the conventional product after hydrolysis is also lower than that of the untreated product.
以上のような結果は、ハロメチル化合物の種類を変えて
ら全く同じで、3扱化架橋した本発明品は加水分解に極
めて安定であり、その数例を表1に示す。表中従来品A
はアミノプロピル結合シリカ、BはN−2−アミノエチ
ル−3−アミノプロピル結合シリカである。又、加水分
解安定性は、それぞれの充てん剤を150に4.6mm
のカラムに充てんし、 pl+9の緩衝液を毎分1ml
の速度で連続7日間通液した後、アデノシンジホスフェ
ートの保持時間を測定して通液前後の比を保持能として
示した。The above results were exactly the same even when the type of halomethyl compound was changed, and the products of the present invention which were tritreated and crosslinked were extremely stable against hydrolysis, and several examples thereof are shown in Table 1. Conventional product A in the table
is aminopropyl-bonded silica, and B is N-2-aminoethyl-3-aminopropyl-bonded silica. In addition, the hydrolytic stability of each filler was 4.6 mm to 150.
Fill the column with 1 ml of pl+9 buffer per minute.
The retention time of adenosine diphosphate was measured, and the ratio before and after the fluid flow was expressed as the retention capacity.
表1 従来品と本発明品の加水分解安定性(保持能)の
比較
保持能
l 従来品A 582
従来品B 703 lを
ビス(クロルメチル)エーテルで3級化架橋したちの
9641を1.2−ジブロモエタンで
3級化架橋したもの 985 !をα
、α°−ジクロローp−キシレンで3級化架橋したもの
9962を1.2−ジブロモエタンで
3級化架橋したちの 9972を1.
3−ジブロモプロパンで
3級化架橋したもの 9982をクロ
ロメチルオキシランで
3級化架橋したもの 99表1で明ら
かなように、pl+9の緩衝液を連続7日間通液すると
、従来品はいずれも加水分解のためカラムの劣化が起り
、保持能も低下している。Table 1 Comparison of hydrolytic stability (retention ability) between conventional product and product of the present invention Conventional product A 582
Conventional product B 703 l is tertiaryized and cross-linked with bis(chloromethyl)ether.
Tertiary crosslinking of 9641 with 1,2-dibromoethane 985! α
9962 was tertiary-crosslinked with α°-dichloro-p-xylene, and 9972 was tertiary-crosslinked with 1,2-dibromoethane.
Tertiary cross-linked product with 3-dibromopropane Tertiary cross-linked product of 9982 with chloromethyloxirane 99 As is clear from Table 1, when a buffer solution of pl + 9 is passed for 7 consecutive days, all conventional products lose hydration. Column deterioration occurs due to decomposition, and retention capacity also decreases.
これに比し本発明品はどのようなハロメチル化合物で3
級化架橋しても極めて安定であることがわかる。これは
極く限られた1例であり、XCl1.R″−CII 、
X 又はXCIIJ’ で表わされるハロメチル化
合物であればすべて同一の安定性を示す。In contrast, the product of the present invention has 3
It can be seen that it is extremely stable even after graded crosslinking. This is a very limited example, and XCl1. R″-CII,
All halomethyl compounds represented by X or XCIIJ' exhibit the same stability.
このように従来使用されている1〜2扱アミノアルキル
結合シリカをハロメチル化合物により3級化架橋すれば
加水分解に安定な優れた充てん剤の得られることがわか
った。次に実施例でさらに詳細に説明する。但しこれに
限定されるものではない。Thus, it has been found that an excellent filler that is stable against hydrolysis can be obtained by tertiating and crosslinking the conventionally used 1-2 treated aminoalkyl-bonded silica with a halomethyl compound. Next, a more detailed explanation will be given in Examples. However, it is not limited to this.
実施例 !
平均粒径5μmの球形シリカゲル50gを3つロフラス
コに入れ、トルエン250m11アミノプロピルジメチ
ルメトキシシラン50g1を順次加え、窒素気流中で1
0時間還流加熱反応した。反応終了後、常法でろ過洗浄
し60℃、減圧下で1夜乾燥した。このアミノプロピル
結合シリカ5gを3つロフラスコに入れ、キシレン20
m1.触媒及び1.3−ジブロモプロパンの所定量を順
次加え、窒素気流下、5時間加熱還流して反応した。反
応終了後、ろ過し、キシレン、エタノール、アセトン、
水で順次洗浄し最後にアセトンで洗浄後、減圧下80℃
で1夜乾燥した。得られた3級化架橋シリカ約100m
gを試験管に採り、ニンヒドリン試液0.5mlを加え
て温浴中で加温し、アミノ基の3級化の程度を調べた。Example ! Three 50 g of spherical silica gels with an average particle size of 5 μm were placed in a Lof flask, and 250 ml of toluene and 50 g of aminopropyldimethylmethoxysilane were sequentially added to the flask.
The reaction was heated under reflux for 0 hours. After the reaction was completed, it was filtered and washed in a conventional manner and dried at 60° C. under reduced pressure overnight. Put three 5g of this aminopropyl-bonded silica into a Lof flask and add 20g of xylene.
m1. Predetermined amounts of catalyst and 1,3-dibromopropane were added one after another, and the mixture was heated under reflux for 5 hours under a nitrogen stream to react. After the reaction is complete, filter, xylene, ethanol, acetone,
After washing sequentially with water and finally with acetone, 80℃ under reduced pressure.
It was dried overnight. Approximately 100 m of the obtained tertiary crosslinked silica
g was placed in a test tube, 0.5 ml of ninhydrin test solution was added, and the mixture was heated in a hot bath to examine the degree of tertiaryization of amino groups.
その結果を1.3−ジブロモプロパン仕込量に対して示
したのが表2である。表中の記号○印は3級化が完全で
ニンヒドリン試薬に陰性のもの、△は弱く着色し未反応
1級アミンがわずかに存在するもの、X印は濃く着色し
かなり多くの1級アミンが残存するものをそれぞれ示す
。Table 2 shows the results with respect to the amount of 1,3-dibromopropane charged. In the table, the symbol ○ indicates that tertiaryization is complete and is negative to the ninhydrin reagent, △ indicates that it is weakly colored and contains a small amount of unreacted primary amine, and the symbol X indicates that it is deeply colored and contains a considerable amount of primary amine. The remaining items are shown below.
表2 アミノプロピル結合シリカの3級化架橋の程度
1.3−ジブロモ 触媒
プロパン仕込量(トリエチルアミン)
0 (g) O(g) X
l 0.5 X2
1.0 △3
1.5 05 2.5
010 5.0
050 25.0 0又、
アミノプロピル結合シリカとそれを5gの1.3−ジブ
ロモプロパンで3級化架橋したものの加水分解安定性が
図1〜3である。Table 2 Degree of tertiary crosslinking of aminopropyl-bonded silica 1.3-dibromo Catalyst Propane charge (triethylamine) 0 (g) O (g) X
l 0.5 X2
1.0 △3
1.5 05 2.5
010 5.0
050 25.0 0 again,
Figures 1 to 3 show the hydrolytic stability of aminopropyl-bonded silica and tertiary crosslinked silica with 5 g of 1,3-dibromopropane.
実施例 2
平均粒径5μmの球形シリカゲル50gを3つロフラス
コに入れ、トルエン250m1. N4−アミノエチル
−3−アミノプロピルトリメトキシシラン55gを順次
加え、窒素気流下で10時間加熱還流して反応した。反
応終了後常法でろ過洗浄し60℃、減圧下で1夜乾燥し
た。このようにして調製したN−2−アミノエチル−3
−アミノプロピル結合シリカ5gを3つロフラスコに入
れ、キシレン20m1゜1.2−ジブロモエタン5gを
それぞれ加え、窒素気流下で5時間加熱還流して反応し
た。反応終了後実施例1と同様な方法で洗浄乾燥し、3
級化架橋物を調製した。これと全く同じ条件で、1.3
−ジブロモプロパン、クロロメチルオキシラン、および
その1:1混合物による3級化架橋反応を行った。Example 2 Three 50 g of spherical silica gels with an average particle size of 5 μm were placed in a flask, and 250 ml of toluene was added. 55 g of N4-aminoethyl-3-aminopropyltrimethoxysilane was successively added, and the mixture was heated under reflux for 10 hours to react. After the reaction was completed, it was filtered and washed in a conventional manner and dried at 60° C. under reduced pressure overnight. N-2-aminoethyl-3 thus prepared
Three 5 g pieces of -aminopropyl-bonded silica were placed in a flask, 20 ml of xylene and 5 g of 1.2-dibromoethane were added to each flask, and the mixture was heated under reflux for 5 hours under a nitrogen stream to react. After the reaction was completed, it was washed and dried in the same manner as in Example 1.
A graded crosslinked product was prepared. Under the same conditions, 1.3
- A tertiary crosslinking reaction was carried out with dibromopropane, chloromethyloxirane, and a 1:1 mixture thereof.
このようにして調製したシリカの加水分解安定性が表1
中の2および6,7.8であり、3級化架橋したものは
いずれら安定である。The hydrolytic stability of the silica thus prepared is shown in Table 1.
Of these, 2, 6, and 7.8, and the tertiary crosslinked ones are stable.
以上の実施例1は一般式で示すと
に相当し、実施例2は
Ni1s −N−C
1lt−R″−CIlt−N−又は
N11゜
CIlt
CI[。The above Example 1 corresponds to the general formula, and Example 2 corresponds to Ni1s -N-C
1lt-R″-CIlt-N- or N11°CIlt CI[.
■
1l
CIlt + X−C11t−R’ + X−CI
lt−11’−CIlt−X −C11゜
I
CIL C11t
CIl、 CIl。■ 1l CIlt + X-C11t-R' + X-CI
lt-11'-CIlt-X -C11゜I CIL C11t CIl, CIl.
Cl1x C11t にそれぞれ対応している。Cl1x C11t corresponds to each.
[効果] 従来のアミノアルキル結合シリカをハロメチ
ル化合物で3級化すると同時にアミノ基間を架橋した結
果、本来の分離特性を損うことなく、試料中のカルボニ
ル化合物その他反応性夾雑物や加水分解時に対して極め
て安定になり、液体クロマトグラフィーの最も重要なカ
ラム寿命を延長できる大きな効果がある。[Effect] As a result of tertiaryizing conventional aminoalkyl-bonded silica with a halomethyl compound and at the same time cross-linking the amino groups, it is possible to eliminate carbonyl compounds and other reactive impurities in the sample and during hydrolysis without impairing the original separation properties. It has the great effect of extending column life, which is the most important aspect of liquid chromatography.
図1は本発明の効果について従来品と比較したもの。図
2は本発明品の分離能を加水分解前後で比較したもの。
図3は従来品の分離能を加水分解前後で比較したもの。
%許田層人東京化成工業株式会社
0 :’to 60 90 12
0 150 180 210加水分解時間(分)
図1 加水分解安定性の比較
保持時間(分)
A、加水分解前
保持時間(分)
B、加水分解処理後
図2 本発明品の分離能力Figure 1 shows a comparison of the effects of the present invention with conventional products. Figure 2 shows a comparison of the separation ability of the product of the present invention before and after hydrolysis. Figure 3 compares the separation performance of the conventional product before and after hydrolysis. % Kyoda Hito Tokyo Chemical Industry Co., Ltd. 0 :'to 60 90 12
0 150 180 210 Hydrolysis time (minutes) Figure 1 Comparison of hydrolysis stability Retention time (minutes) A. Retention time before hydrolysis (minutes) B. After hydrolysis treatment Figure 2 Separation ability of the product of the present invention
Claims (1)
NH)_0_〜_1_0−CH_2CH_2NH_2で
表わされるアミノアルキル結合シリカを、XCH_2R
′又はXC_2R″CH_2Xで表わされるハロメチル
化合物の単独又は混合物と反応してアミノ基間を架橋す
ると同時にそのアミノ基を3級化することを特長とする
新規なアミノアルキル結合シリカの加水分解安定化方法 但しXはハロゲン原子、Rは炭素数2〜10の炭化水素
残基、R′はC_nH_2_n_−_1Oで表わされる
エポキシ残基、C_nH_2_n_+_1Oのエーテル
残基、▲数式、化学式、表等があります▼のアルキルフ
ェニル基等を意味する。又R″は、C_nH_2_nの
炭化水素残基、COのカルボニル基、S原子、▲数式、
化学式、表等があります▼のフェニレン基、 ▲数式、化学式、表等があります▼のアルコール残基等
を意味しnは 1〜10の整数である。[Claims] ≡SiRNH_2 or ≡SiRNH(CH_2CH_2
NH)_0_~_1_0-CH_2CH_2NH_2, XCH_2R
A novel method for hydrolytically stabilizing aminoalkyl-bonded silica, which is characterized by reacting with a halomethyl compound represented by ' or Where, R″ means a phenyl group, etc. Also, R″ is a hydrocarbon residue of C_nH_2_n, a carbonyl group of CO, an S atom, ▲ formula,
There are chemical formulas, tables, etc. ▼ Phenylene group, ▲ Numerical formulas, chemical formulas, tables, etc. ▼ means alcohol residues, etc. n is an integer from 1 to 10.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP62251685A JPH0196009A (en) | 1987-10-07 | 1987-10-07 | Method for stabilizing against hydrolysis of aminoalkyl silica by crosslinking together with transforming amino groups into tertiary forms |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP62251685A JPH0196009A (en) | 1987-10-07 | 1987-10-07 | Method for stabilizing against hydrolysis of aminoalkyl silica by crosslinking together with transforming amino groups into tertiary forms |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH0196009A true JPH0196009A (en) | 1989-04-14 |
Family
ID=17226487
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP62251685A Pending JPH0196009A (en) | 1987-10-07 | 1987-10-07 | Method for stabilizing against hydrolysis of aminoalkyl silica by crosslinking together with transforming amino groups into tertiary forms |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH0196009A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04166764A (en) * | 1990-10-31 | 1992-06-12 | Shiseido Co Ltd | Packing agent for liquid chromatography and preparation thereof |
-
1987
- 1987-10-07 JP JP62251685A patent/JPH0196009A/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04166764A (en) * | 1990-10-31 | 1992-06-12 | Shiseido Co Ltd | Packing agent for liquid chromatography and preparation thereof |
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