JPH0764541B2 - Method for producing inner hydrophobic silica gel - Google Patents
Method for producing inner hydrophobic silica gelInfo
- Publication number
- JPH0764541B2 JPH0764541B2 JP63207943A JP20794388A JPH0764541B2 JP H0764541 B2 JPH0764541 B2 JP H0764541B2 JP 63207943 A JP63207943 A JP 63207943A JP 20794388 A JP20794388 A JP 20794388A JP H0764541 B2 JPH0764541 B2 JP H0764541B2
- Authority
- JP
- Japan
- Prior art keywords
- silica gel
- group
- hydrophobic
- filler
- hydrolysis
- 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.)
- Expired - Fee Related
Links
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims description 69
- 239000000741 silica gel Substances 0.000 title claims description 51
- 229910002027 silica gel Inorganic materials 0.000 title claims description 51
- 230000002209 hydrophobic effect Effects 0.000 title claims description 32
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 239000011148 porous material Substances 0.000 claims description 17
- 125000000962 organic group Chemical group 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 6
- 239000000945 filler Substances 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000012856 packing Methods 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000006460 hydrolysis reaction Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000007062 hydrolysis Effects 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 150000002009 diols Chemical group 0.000 description 10
- 125000001165 hydrophobic group Chemical group 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 8
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 8
- -1 cyanopropyl group Chemical group 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229960004559 theobromine Drugs 0.000 description 4
- 229960000278 theophylline Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 125000005372 silanol group Chemical group 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- GZGREZWGCWVAEE-UHFFFAOYSA-N chloro-dimethyl-octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[Si](C)(C)Cl GZGREZWGCWVAEE-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- LXWLHXNRALVRSL-UHFFFAOYSA-N 3-(oxiran-2-ylmethoxy)propylsilane Chemical compound [SiH3]CCCOCC1CO1 LXWLHXNRALVRSL-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 238000004438 BET method Methods 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 125000004966 cyanoalkyl group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- BPSIOYPQMFLKFR-UHFFFAOYSA-N trimethoxy-[3-(oxiran-2-ylmethoxy)propyl]silane Chemical compound CO[Si](OC)(OC)CCCOCC1CO1 BPSIOYPQMFLKFR-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
Landscapes
- Silicon Compounds (AREA)
Description
【発明の詳細な説明】 （技術分野） 本発明は、内面疎水型シリカゲルの製造方法に係り、特
にシリカゲルの細孔内部が疎水性とされる一方、その外
表面が親水性とされた、液体クロマトグラフィー用カラ
ム充填剤等として有用な内面疎水型シリカゲルを容易に
製造することのできる方法に関するものである。Description: TECHNICAL FIELD The present invention relates to a method for producing an inner surface hydrophobic silica gel, and in particular, a liquid in which the inside of the pores of silica gel are made hydrophobic and the outer surface thereof is made hydrophilic. The present invention relates to a method capable of easily producing an inner hydrophobic silica gel useful as a column packing for chromatography and the like.
（背景技術） この種の内面疎水型（逆相型）充填剤は、その内面たる
細孔内部に疎水性基が導入され、また外表面には親水性
基が導入された複合構造を有しているところから、この
ような内面疏水型充填剤を用いて試料の分離分析を行な
った場合に、分子量の大きなタンパク質のような分子
は、かかる充填剤の立体的に小さな細孔内部に侵入する
ことができないため、細孔内部の疎水性基による疎水性
相互作用を受けることなく直ちにカラムから溶出される
一方、比較的低分子量の小さな分子は細孔内部に侵入で
き、その細孔内部の疎水性の環境によって、通常のC18
型充填剤と同様に、疎水性相互作用によって保持される
こととなる。(Background Art) This kind of inner surface hydrophobic type (reverse phase type) filler has a composite structure in which a hydrophobic group is introduced inside the pores which are the inner surface and a hydrophilic group is introduced on the outer surface. Therefore, when a sample is separated and analyzed using such an inner surface hydrophobic type packing material, a molecule such as a protein having a large molecular weight penetrates into the sterically small pores of the packing material. Since it is not possible to elute from the column immediately without being subjected to hydrophobic interaction due to the hydrophobic group inside the pore, small molecules with a relatively low molecular weight can enter inside the pore and Normal C 18 depending on sexual environment
Like the mold filler, it will be retained by hydrophobic interactions.
つまり、試料分子の認識能は、充填剤の細孔内部に試料
分子が侵入できるかどうかによって決定されるのであ
り、この内面疎水型の充填剤の細孔の大きさを適宜に設
定することによって、一般のC18型充填剤では分析前に
吸着されてしまうようなタンパク質等の高分子を、事前
に除去する必要がなくなるのである。それ故、このよう
な内面疎水型充填剤を用いれば、タンパク質等を含む試
料を前処理することなく分析することが可能となるので
ある。In other words, the ability to recognize sample molecules is determined by whether or not the sample molecules can penetrate inside the pores of the packing material, and by appropriately setting the size of the pores of this inner surface hydrophobic packing material. , It is not necessary to remove in advance a polymer such as a protein that is adsorbed before analysis by a general C 18 type packing material. Therefore, by using such an inner surface hydrophobic packing material, it becomes possible to analyze a sample containing proteins and the like without pretreatment.
ところで、このような内面疎水性型充填剤の合成手法と
しては、従来から、特開昭61−65159号公報に示される
如き、酵素を用いて充填剤の外表面の疎水基を分解する
方法や、特開昭62−158113号公報に示されている如き、
プラズマ処理によって充填剤の外表面の疎水性基を脱離
せしめて、目的とする充填剤を得る方法等が、提案され
ている。By the way, as a method for synthesizing such an inner surface hydrophobic type filler, conventionally, as shown in JP-A-61-65159, a method of decomposing the hydrophobic group on the outer surface of the filler using an enzyme or , As disclosed in JP-A-62-158113,
A method has been proposed in which the hydrophobic group on the outer surface of the filler is removed by plasma treatment to obtain the desired filler.
しかしながら、前者の手法では、充填剤の疎水性基の分
解に酵素反応が用いられることとなるところから、反応
速度の遅い酵素反応の故に合成時間が長くなることが避
けられず、また、使用すべき酵素が高価であったり、更
には、シリカゲルの表面に導入された官能基を分解する
ことのできる酵素が存在しなければ、外表面の疎水性基
を分解処理出来ないために、固定相の種類に限界がある
等、その合成に多くの制約を受けるという問題が存在す
るのである。However, in the former method, the enzymatic reaction is used for decomposing the hydrophobic group of the packing material, and therefore the synthesis time is unavoidably lengthened due to the enzymatic reaction having a slow reaction rate, and it cannot be used. If the enzyme to be used is expensive, or if there is no enzyme capable of decomposing the functional group introduced on the surface of silica gel, the hydrophobic group on the outer surface cannot be decomposed. There is a problem that there are many restrictions on the composition, such as limited types.
また、後者のプラズマを使用する合成方法においては、
高いエネルギーを有するプラズマを用いることから、充
填剤外表面のシリル化剤分子の分解の他に、分子の再結
晶の可能性があり、効率的且つ選択的な分子の切断は困
難と推定され、充填剤の外表面から疎水性基を均一に剥
離するためには繰り返しの反応が必要であると考えられ
るのであり、更には、プラズマを使用するには減圧等の
条件が必要となって、結局、内面疎水型の充填剤を合成
する際の製造行程が煩雑になってしまうという問題を内
在してしる。Also, in the latter synthesis method using plasma,
Since a plasma having high energy is used, it is presumed that efficient and selective cleavage of the molecule is difficult because of the possibility of recrystallizing the molecule in addition to the decomposition of the silylating agent molecule on the outer surface of the packing, It is considered that a repeated reaction is necessary to uniformly remove the hydrophobic group from the outer surface of the filler, and further, conditions such as depressurization are required to use plasma, and eventually, However, there is an inherent problem that the manufacturing process when synthesizing the hydrophobic filler on the inner surface becomes complicated.
以上の理由から、上記した従来法に代わる、内面逆相型
充填剤のより簡易な合成方法の出現が、望まれているの
である。For the above reasons, the appearance of a simpler synthetic method for the inner surface reverse phase type filler, which is an alternative to the above-mentioned conventional method, is desired.
（解決課題） ここにおいて、本発明は、かかる事情を背景にして為さ
れたものであって、その解決課題とするところは、前述
の如き内面疎水型のシリカゲルを、幅広く、しかもより
簡単に得られるようにすることにある。(Problem to be Solved) Here, the present invention has been made in view of such circumstances, and the problem to be solved is to obtain a wide range of inner hydrophobic silica gel as described above and more easily. To be able to do so.
（解決手段） そして、本発明は、上述の如き課題解決のために、細孔
を有する多孔性シリカゲルの内外面に、所定のシリル化
剤との反応によって疎水性有機基を結合せしめた後、該
多孔性シリカゲルを酸性媒体中で処理することにより、
かかる多孔性シリカゲルの外表面に結合する疎水性有機
基を分解除去することを特徴とする内面疎水型シリカゲ
ルの製造方法を、その要旨とするものである。(Solution) In order to solve the problems as described above, the present invention provides, on the inner and outer surfaces of porous silica gel having pores, after binding a hydrophobic organic group by a reaction with a predetermined silylating agent, By treating the porous silica gel in an acidic medium,
The gist is a method for producing an inner hydrophobic silica gel, which is characterized by decomposing and removing a hydrophobic organic group bonded to the outer surface of such porous silica gel.
（具体的構成） ところで、かかる本発明手法に従って、内面のみが疎水
化せしめられるシリカゲルとしては、通常の、細孔を有
する多孔性のシリカゲルが用いられ、またその細孔の孔
径は、例えば、分析しようとする試料に含まれて分析に
有害なタンパク質等の高分子が入り込まない大きさにな
るように、適宜に選定されることとなる。(Specific configuration) By the way, according to the method of the present invention, as the silica gel of which only the inner surface is hydrophobized, an ordinary porous silica gel having pores is used, and the pore diameter of the pores is, for example, analyzed. Appropriate selection will be made so that the macromolecules such as proteins contained in the sample to be analyzed and harmful to the analysis do not enter.
そして、そのようなシリカゲルに対して、その内外面
に、所定のシリル化剤との反応によって疎水性有機基が
結合せしめられるのである。なお、このシリカゲルに結
合、導入される疎水性有機基としては、シリカゲルの使
用目的等に応じて適宜選択され、例えば、液体クロマト
グラフィー用のカラム充填剤等として用いる場合には、
プロピル基、オクチル基、オクタデシル基等のアルキル
基、シアノプロピル基等のシアノアルキル基、或いはア
ミノプロピル基等のアミノアルキル基などが挙げられ
る。また、そのような疎水性有機基を与えるシリル化剤
としては、公知の各種のものが採用可能であり、その反
応条件も、選択されたシリル化剤に応じて適宜に決定さ
れる。Then, with respect to such silica gel, a hydrophobic organic group is bound to the inner and outer surfaces thereof by a reaction with a predetermined silylating agent. The hydrophobic organic group bound to and introduced into the silica gel is appropriately selected according to the intended use of the silica gel and, for example, when used as a column packing material for liquid chromatography,
Examples thereof include an alkyl group such as a propyl group, an octyl group and an octadecyl group, a cyanoalkyl group such as a cyanopropyl group, and an aminoalkyl group such as an aminopropyl group. As the silylating agent that gives such a hydrophobic organic group, various known silylating agents can be adopted, and the reaction conditions thereof are appropriately determined depending on the selected silylating agent.
次いで、この内外面に疎水性有機基が結合せしめられた
シリカゲルに対して、酸性媒体中、一般には酸水溶液中
における処理操作が施され、かかるシリカゲルの外表面
に結合する疎水性有機基が加水分解されて、除去せしめ
られるのである。なお、この酸性媒体処理に用いられる
酸としては、例えば、塩酸、硝酸、硫酸、燐酸の如き鉱
酸（無機酸）などが挙げられ、また必要に応じて、その
ような酸性媒体には、シリカゲルとの親和性を高めるた
めに、水と共に、メタノール等の溶媒が混入されること
となる。また、かかる加水分解の処理手法としては、例
えば、激しい撹拌の下での濃い酸水溶液を用いた還流操
作が採用されることとなる。Next, the silica gel having the hydrophobic organic groups bound to its inner and outer surfaces is subjected to a treatment operation in an acidic medium, generally an acid aqueous solution, so that the hydrophobic organic groups bound to the outer surfaces of the silica gel are hydrolyzed. It is decomposed and removed. Examples of the acid used in the acidic medium treatment include mineral acids (inorganic acids) such as hydrochloric acid, nitric acid, sulfuric acid and phosphoric acid. If necessary, such acidic medium may be silica gel. In order to increase the affinity with, a solvent such as methanol is mixed with water. Further, as a method of treating such hydrolysis, for example, a reflux operation using a concentrated aqueous acid solution under vigorous stirring will be adopted.
このように、単なる酸性媒体中での処理という非常に簡
単な処理操作を施すことで、シリカゲルの外表面の疎水
性基のみが選択的に加水分解せしめられ得るのであり、
しかも、酵素のように分解されるべき疎水性基を選ぶこ
ともなく、以て、内面が疎水性であり、外面が親水性で
ある内面疎水型（逆相型）のシリカゲルを、容易に且つ
幅広く製造することが可能になったのである。Thus, by performing a very simple treatment operation of simply treating in an acidic medium, only the hydrophobic groups on the outer surface of silica gel can be selectively hydrolyzed,
Moreover, without selecting a hydrophobic group to be decomposed like an enzyme, an inner surface hydrophobic type (reverse phase type) silica gel in which the inner surface is hydrophobic and the outer surface is hydrophilic can be easily and It has become possible to manufacture a wide range.
そして、この加水分解処理の後、更に必要に応じて、シ
リカゲルの外表面の親水性基（シラノール基）に、ジオ
ール基等を有する親水性基が導入されることによって、
充填剤の外表面における親水性がより高められるのであ
る。Then, after this hydrolysis treatment, if necessary, a hydrophilic group having a diol group or the like is introduced into the hydrophilic group (silanol group) on the outer surface of the silica gel,
The hydrophilicity on the outer surface of the filler is further enhanced.
（実施例） 以下に、本発明の幾つかの実施例を示し、本発明を更に
具体的に明らかにすることとするが、本発明が、そのよ
うな実施例の記載によって、何等の制約をも受けるもの
でないことは、言うまでもないところである。(Examples) Hereinafter, several examples of the present invention will be shown to clarify the present invention more specifically, but the present invention does not impose any restrictions due to the description of such examples. Needless to say, it is not something to receive.
また、本発明には、以下の実施例の他にも、更には上記
の具体的記述以外にも、本発明の趣旨を逸脱しない限り
において、当業者の知識に基づいて種々なる変更、修
正、改良等を加え得るものであることが、理解されるべ
きである。In addition to the following embodiments, the present invention further includes various changes and modifications based on the knowledge of those skilled in the art, in addition to the above specific description, without departing from the spirit of the present invention. It should be understood that improvements and the like can be added.
なお、以下に示される部及び百分率は、特に断りのない
限り、重量を基準とするものである。The parts and percentages shown below are based on weight unless otherwise specified.
実施例 １ 予め、通常の多孔性シリカゲルを6Nの塩酸で洗浄した
後、このシリカゲルに、20mmHgの減圧下において、150
℃で３時間の間、加熱減圧乾燥を行なった。なお、この
シリカゲルの平均細孔径は110Åであった。Example 1 Conventional porous silica gel was washed with 6N hydrochloric acid in advance, and then this silica gel was subjected to 150 mm under reduced pressure of 150 mmHg.
Heating under reduced pressure was carried out for 3 hours at ℃. The average pore size of this silica gel was 110Å.
次いで、このシリカゲル:10部に対して、オクタデシル
ジメチルクロロシラン:10部を、ピリジン:3部を触媒と
して、トルエン中で、６時間、還流することによって、
前記シリカゲルの内外面（細孔内面および外表面）の全
面にオクタデシル基（オクタデシルジメチルシリル基）
が導入された、ODS（オクタデシルジメチルシリル化）
シリカ（C18型充填剤）を合成した。Then, with respect to 10 parts of this silica gel, 10 parts of octadecyldimethylchlorosilane was refluxed in toluene for 6 hours using 3 parts of pyridine as a catalyst.
Octadecyl group (octadecyldimethylsilyl group) on the entire inner and outer surfaces (inner and outer surfaces of the pores) of the silica gel.
Was introduced, ODS (octadecyldimethylsilylation)
Silica (C 18 type filler) was synthesized.
そして、この得られたODSシリカ:1gに対して、メタノー
ル:6Nの各種鉱酸水溶液＝70容量％:30容量％の混合溶液
が20mlとなる割合で、かかるシリカゲルを該混合溶液中
に投入し、１〜５時間の処理時間において、加熱温度:1
00℃の下で、激しく撹拌（約1000rpm）しながら、それ
ぞれ還流操作を施して、加水分解反応を行なった。な
お、6Nの鉱酸としては、塩酸、硝酸、硫酸を使用した。Then, with respect to 1 g of the obtained ODS silica, a mixed solution of various mineral acid aqueous solutions of methanol: 6N = 70% by volume: 30% by volume was added to the mixed solution at a rate of 20 ml. Heating temperature: 1 to 5 hours, heating temperature: 1
Hydrolysis reaction was carried out under reflux at 00 ° C under vigorous stirring (about 1000 rpm). As the 6N mineral acid, hydrochloric acid, nitric acid, and sulfuric acid were used.
その後、この加水分解されたシリカゲル:10部と３−グ
リシドオキシプロピルトリメトキシシラン:9部とを、水
を溶媒として混合せしめて、５時間の還流操作を実施し
て反応せしめ、加水分解されたシリカゲルに生じたシラ
ノール基にジオール基を有する有機基を導入した。Then, 10 parts of this hydrolyzed silica gel and 9 parts of 3-glycidoxypropyltrimethoxysilane were mixed with water as a solvent, and a reflux operation was carried out for 5 hours to cause a reaction. An organic group having a diol group was introduced into the silanol group generated on the silica gel.
そして、それら加水分解時間および使用酸触媒を異にし
て得られた各種のシリカ充填剤を、液体クロマトグラフ
のカラムに充填した後、メタノール：水＝60:40（容量
比）の溶媒を移動相として、各種のシリカ充填剤におけ
るトルエンのキャパシティー比:k′をそれぞれ測定し、
第１図に、その結果を示した。Then, after packing various silica packings obtained with different hydrolysis times and acid catalysts used in the column of a liquid chromatograph, a solvent of methanol: water = 60: 40 (volume ratio) was used as a mobile phase. As, the capacity ratio of toluene in various silica filler: k'is measured,
The results are shown in FIG.
なお、カラムは、内径:4.6mm、長さ:150mmのステンレス
スチール製のカラムを用い、充填剤のカラムへの充填方
法は、湿式充填法を採用した。A column made of stainless steel having an inner diameter of 4.6 mm and a length of 150 mm was used as the column, and a wet packing method was adopted as a method of packing the packing material into the column.
また、液体クロマトグラフシステムは、島津LC−6A型送
液ポンプ、Reodyne7125型ループインジェクター、島津S
PD−6A型UV検出器、島津CR−5A型データ処理器から構成
され、また、クロマトグラフィ操作は30℃に保温した状
態で行なわれた。In addition, the liquid chromatograph system is Shimadzu LC-6A type liquid delivery pump, Reodyne 7125 type loop injector, Shimadzu S
It consisted of PD-6A type UV detector and Shimadzu CR-5A type data processor, and the chromatography operation was carried out while keeping the temperature at 30 ° C.
かかる第１図の結果から、加水分解反応の時間の経過に
従い、シリカ充填剤におけるトルエンの保持の大きさを
表わすｋ′の値が減少することから、充填剤のアルキル
シリル化剤（オクタデシルジメチルシリル基）が加水分
解されていることが分かった。また、加水分解の速度
は、塩酸を触媒に使用した時が最も早く、以下、硝酸、
硫酸の順に加水分解速度は低下する傾向が見られた。From the results shown in FIG. 1, the value of k'representing the degree of retention of toluene in the silica filler decreases with the lapse of time of the hydrolysis reaction, so that the alkylsilylating agent (octadecyldimethylsilyl) of the filler is decreased. It was found that the (group) was hydrolyzed. In addition, the rate of hydrolysis is the fastest when hydrochloric acid is used as a catalyst.
The hydrolysis rate tended to decrease in the order of sulfuric acid.
実施例 ２ 先ず、多孔性のシリカゲルを6N塩酸で洗浄した後、この
シリカゲルに、20mmHgの減圧下において、150℃で３時
間、加熱減圧乾燥を実施した。なお、このシリカゲル
は、粒径：約５μｍ、細孔径：約60Åであり、窒素吸着
法（BET法）による測定の結果、下記第１表に示される
物性を示した。また、ゲル浸透クロマトグラフィーの検
量線から算出された試料分子の排除限界は、分子量約20
000程度と推定された。Example 2 First, porous silica gel was washed with 6N hydrochloric acid, and then this silica gel was dried under reduced pressure with heating at 150 ° C. for 3 hours under reduced pressure of 20 mmHg. The silica gel had a particle size of about 5 μm and a pore size of about 60 liters, and as a result of measurement by a nitrogen adsorption method (BET method), exhibited the physical properties shown in Table 1 below. The exclusion limit of sample molecules calculated from the calibration curve of gel permeation chromatography is about 20
It was estimated to be around 000.
次いで、このシリカゲル:10部に対して、オクタデシル
ジメチルクロロシラン:13部を用いて、３部のピリジン
を触媒として、トルエン中で、６時間、還流することに
よって、かかるシリカゲルの内外面にオクタデシル基
（オクタデシルジメチルシリル基）を導入し、ODSシリ
カを合成した。 Next, with respect to 10 parts of this silica gel, 13 parts of octadecyldimethylchlorosilane was used as a catalyst, and 3 parts of pyridine was used as a catalyst, and the mixture was refluxed in toluene for 6 hours to give an octadecyl group ( Octadecyldimethylsilyl group) was introduced to synthesize ODS silica.
そして、このように合成されたODSシリカ:1gに対して、
11N塩酸:20mlの割合で、それらを混和せしめ、加熱温
度:100℃にて、激しく撹拌（約1000rpm）しながら還流
し、第２図に示される各種時間において加水分解を行な
った。And, with respect to ODS silica thus synthesized: 1 g,
They were mixed at a ratio of 11N hydrochloric acid: 20 ml, heated at a heating temperature of 100 ° C., refluxed with vigorous stirring (about 1000 rpm), and hydrolyzed at various times shown in FIG.
その後、かかる加水分解操作の施された各シリカゲル:1
0部に対して、３−グリシドオキシプロピルシラン:9部
を用い、それらを、水を溶媒として混和せしめ、５時間
の還流操作により反応させることにより、加水分解にて
形成された、かかるシリカゲルの外表面のシラノール基
に、ジオール基を有する有機基を導入した。Then, each silica gel subjected to such a hydrolysis operation: 1
Such a silica gel formed by hydrolysis by using 9 parts of 3-glycidoxypropylsilane: 9 parts with respect to 0 part, mixing them with water as a solvent and reacting by refluxing for 5 hours. An organic group having a diol group was introduced into the silanol group on the outer surface of the.
そして、これらのシリカゲルの反応時間による加水分解
の反応状況を調べるために、４つの物質（トルエン、ベ
ンゼン、メチルベンゾエート、アセトフェノン）を用い
てキャパシティー比:k′を測定し、その結果を第２図に
示した。なお、移動相やカラム、測定装置等は、前記実
施例１と同様である。Then, in order to investigate the reaction status of the hydrolysis of these silica gels depending on the reaction time, the capacity ratio: k ′ was measured using four substances (toluene, benzene, methylbenzoate, acetophenone), and the results were As shown in the figure. The mobile phase, column, measuring device, etc. are the same as in Example 1.
かかる第２図の結果から、ｋ′の値は、何れも５時間ま
でに速やかに低下し、その後非常に僅かずつ低下してい
ることが分かり、シリカゲル（充填剤）の加水分解反応
は、ほぼ５時間以内に大部分が完了しているものと考え
られた。From the results shown in FIG. 2, it was found that the values of k ′ all rapidly decreased by 5 hours and then decreased very little by little, and the hydrolysis reaction of silica gel (filler) was almost the same. It was considered that most were completed within 5 hours.
実施例 ３ 実施例２において得られた、オクタデシル基が内外面に
導入されたシリカゲル、長時間の加水分解処理が施され
て、外表面部のオクタデシル基が分解除去されたシリカ
ゲル、オクタデシル基が除去された外表面部にジオール
基が導入されたシリカゲルの、それぞれの炭素の含有率
を測定した結果、下記第２表の結果が得られた。Example 3 The silica gel in which the octadecyl group was introduced into the inner and outer surfaces obtained in Example 2, the silica gel in which the octadecyl group on the outer surface portion was decomposed and removed by a long-term hydrolysis treatment, and the octadecyl group were removed. As a result of measuring the carbon content of each of the silica gels having a diol group introduced on the outer surface thereof, the results shown in Table 2 below were obtained.
この結果、加水分解反応が完了した後にも、かなりの炭
素が残存していることから、シリカゲルの細孔内に、オ
クタデシル基が加水分解されずに残されていることが考
察できる。 As a result, since considerable carbon remains even after the hydrolysis reaction is completed, it can be considered that the octadecyl group remains in the pores of the silica gel without being hydrolyzed.
実施例 ４ 実施例２において得られた、５時間の加水分解の後にジ
オール基が導入されたシリカゲルを用いて、かかる充填
剤のクロマトグラフィ的評価を行ない、その結果を第３
図（ａ）に示した。なお、その評価方法としては、血清
中の薬物を分析する場合を想定し、タンパク質として牛
血清アルブミン、低分子量の薬物のモデル試料としてテ
オブロミン及びテオフィリンを使用し、これらを充填カ
ラムに同時に注入することで、分析、評価した。また、
比較のために、C18型充填剤、およびタンパク質のゲル
浸透クロマトグラフィ分析に使用されるジオール充填剤
を用いて、同様の分析を行ない、これらの結果を、それ
ぞれ、第３図（ｂ）及び（ｃ）に示した。Example 4 The silica gel in which a diol group was introduced after hydrolysis for 5 hours obtained in Example 2 was subjected to a chromatographic evaluation of such a filler, and the result was evaluated as a third sample.
It is shown in FIG. As an evaluation method, assuming the case of analyzing a drug in serum, use bovine serum albumin as a protein, theobromine and theophylline as a model sample of a low molecular weight drug, and inject them into a packed column at the same time. Then, it was analyzed and evaluated. Also,
For comparison, a similar analysis was carried out using a C 18 type packing material and a diol packing material used for gel permeation chromatography analysis of proteins, and these results are shown in FIGS. 3 (b) and (b), respectively. It is shown in c).
なお、移動相としては、メタノール：緩衝液＝10:90
（容量比）の溶液（但し、緩衝液は、0.2Mの硫酸ナトリ
ウムを含む、pHが７である0.01Mリン酸緩衝液である）
が用いられ、カラムや測定装置等は、前記実施例１と同
様のものが使用された。The mobile phase was methanol: buffer = 10:90.
(Volume ratio) solution (however, the buffer solution is 0.01M phosphate buffer solution containing 0.2M sodium sulfate and having a pH of 7)
The same column, measuring device, and the like as those used in Example 1 were used.
また、C18型充填剤は、シリカゲルにオクタデシル基を
導入後、更にトルエン中にて、トリメチルクロロシラン
と５時間還流して得られた充填剤であり、ジオール充填
剤は、シリカゲルの内外面に、2,3−ジビドロキシプロ
ポキシプロピル基を導入して得られた充填剤である。The C 18 type filler is a filler obtained by introducing an octadecyl group into silica gel and then refluxing it with trimethylchlorosilane for 5 hours in toluene, and the diol filler is the inner and outer surfaces of the silica gel. It is a filler obtained by introducing a 2,3-dividoxypropoxypropyl group.
かくの如き分析の結果、第３図（ｂ）に示されるC18型
充填剤のクロマトグラムにおいては、タンパク質を表わ
すピークが見られないことから（左の大きなピークは、
アルブミンに含まれる塩類である）、タンパク質は充填
剤の疎水性の外表面にゲル化されたものと考えられた。
また、第３図（ｃ）に示されるジオール充填剤のクロマ
トグラムにおいては、充填剤の内外面が親水性であり、
その表面に試料物質を固定することが困難なため、試料
物質が分離されていないのである。As a result of such an analysis, in the chromatogram of the C 18 -type packing material shown in FIG. 3 (b), no peak representing a protein was found (the large peak on the left is
The proteins, which are the salts contained in albumin), were considered to be gelled on the hydrophobic outer surface of the filler.
Further, in the chromatogram of the diol filler shown in FIG. 3 (c), the inner and outer surfaces of the filler are hydrophilic,
Since it is difficult to fix the sample substance on the surface, the sample substance is not separated.
これに対して、本発明に従う手法によって製造されたシ
リカゲルにおいては、第３図（ａ）に示されるように、
テオブロミンおよびテオフィリンとも良好に分離し、牛
血清アルブミンに対してもジオール充填剤と同程度のピ
ーク面積を示し、充填剤から良好に回収されることを示
している。従って、この充填剤は、外表面は親水性で、
細孔内部が疎水性である内面疎水型の充填剤であること
が確認された。On the other hand, in the silica gel produced by the method according to the present invention, as shown in FIG.
It is well separated from theobromine and theophylline, and has the same peak area as bovine serum albumin as the diol filler, indicating that it is well recovered from the filler. Therefore, this filler has a hydrophilic outer surface,
It was confirmed that the inside of the pores was hydrophobic and was a hydrophobic type filler.
なお、第３図（ａ）及び（ｂ）において、中央のピーク
がテオブロミンを表わし、右のピークがテオフィリンを
表している。3 (a) and 3 (b), the central peak represents theobromine and the right peak represents theophylline.
（発明の効果） 以上の説明から明らかなように、本発明に従うシリカゲ
ルの製造方法によれば、内面疎水型のシリカゲルを、従
来の手法に比べて、非常に簡易な処理にて、しかも分解
すべき疎水性有機基を選ばずに、幅広く製造することが
できるようになったのであり、そこに、本発明の大きな
工業的意義が存在するのである。(Effects of the Invention) As is clear from the above description, according to the method for producing silica gel of the present invention, the hydrophobic silica gel of the inner surface can be decomposed by a very simple process as compared with the conventional method. It has become possible to produce a wide range of products without selecting the hydrophobic organic group to be used, and there is a great industrial significance of the present invention.
第１図は、塩酸、硝酸、硫酸の３種類の酸に関して、オ
クタデシルジメチルシリル基の加水分解の進行具合を表
わすトルエンのキャパシティー比:k′の、時間による変
化を示すグラフであり、第２図は、塩酸を触媒とした時
の、オクタデシルジメチルシリル基の加水分解の進行具
合を表わす、各物質のキャパシティー比:k′の時間によ
る変化を示すグラフであり、更に、第３図（ａ）は、内
面疎水型のシリカゲルを、第３図（ｂ）は、C18型シリ
カゲルを、そして第３図（ｃ）は、ジオール型シリカゲ
ルを、充填剤として用いた時の、牛血清アルブミン、テ
オブロミン及びテオフィリンのクロマトグラムである。FIG. 1 is a graph showing changes with time of the capacity ratio of toluene: k ′, which indicates the progress of hydrolysis of octadecyldimethylsilyl group, with respect to three kinds of acids, hydrochloric acid, nitric acid, and sulfuric acid. The figure is a graph showing the progress of the hydrolysis of the octadecyldimethylsilyl group when using hydrochloric acid as a catalyst, which shows the change in the capacity ratio: k ′ of each substance with time. ) Is an internal hydrophobic silica gel, FIG. 3 (b) is a C 18 silica gel, and FIG. 3 (c) is a diol silica gel as bovine serum albumin, It is a chromatogram of theobromine and theophylline.
Claims (1)
に、所定のシリル化剤との反応によって疎水性有機基を
結合せしめた後、該多孔性シリカゲルを酸性媒体中で処
理することにより、かかる多孔性シリカゲルの外表面に
結合する疎水性有機基を分解除去することを特徴とする
内面疎水型シリカゲルの製造方法。1. A hydrophobic organic group is bound to the inner and outer surfaces of a porous silica gel having pores by a reaction with a predetermined silylating agent, and the porous silica gel is treated in an acidic medium. A method for producing an inner hydrophobic silica gel, which comprises decomposing and removing a hydrophobic organic group bonded to the outer surface of the porous silica gel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63207943A JPH0764541B2 (en) | 1988-08-22 | 1988-08-22 | Method for producing inner hydrophobic silica gel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63207943A JPH0764541B2 (en) | 1988-08-22 | 1988-08-22 | Method for producing inner hydrophobic silica gel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0259415A JPH0259415A (en) | 1990-02-28 |
| JPH0764541B2 true JPH0764541B2 (en) | 1995-07-12 |
Family
ID=16548106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63207943A Expired - Fee Related JPH0764541B2 (en) | 1988-08-22 | 1988-08-22 | Method for producing inner hydrophobic silica gel |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0764541B2 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03218458A (en) * | 1989-10-02 | 1991-09-26 | Shiseido Co Ltd | Column packing material and its production |
| JPH0750092B2 (en) * | 1990-05-30 | 1995-05-31 | ダイソー株式会社 | Method for separating water-soluble organic matter |
| JP4634552B2 (en) * | 1999-03-26 | 2011-02-16 | 株式会社 皇漢薬品研究所 | Method for producing purified propolis extract from which insoluble components have been removed and purified propolis extract from which insoluble components have been removed |
| WO2001083369A1 (en) | 2000-04-28 | 2001-11-08 | Mitsui Chemicals, Inc. | Water-repellent porous silica, method for preparation thereof and use thereof |
| EP1291080A3 (en) * | 2001-09-10 | 2004-05-19 | Tosoh Corporation | Process for production of partially hydrophilized porous adsorbents |
| JP5154973B2 (en) * | 2008-02-20 | 2013-02-27 | 富士シリシア化学株式会社 | Silica gel, chromatographic apparatus, separation method, and method for producing silica gel |
| CN116212086B (en) * | 2022-11-17 | 2024-08-06 | 青岛海诺生物工程有限公司 | Waterproof breathable band-aid and preparation process thereof |
-
1988
- 1988-08-22 JP JP63207943A patent/JPH0764541B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0259415A (en) | 1990-02-28 |
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