JPH034557B2 - - Google Patents
Info
- Publication number
- JPH034557B2 JPH034557B2 JP61201490A JP20149086A JPH034557B2 JP H034557 B2 JPH034557 B2 JP H034557B2 JP 61201490 A JP61201490 A JP 61201490A JP 20149086 A JP20149086 A JP 20149086A JP H034557 B2 JPH034557 B2 JP H034557B2
- Authority
- JP
- Japan
- Prior art keywords
- tert
- butyldimethylchlorosilane
- butyldimethylsilane
- products
- chlorine
- 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
Links
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 10
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 10
- 150000008282 halocarbons Chemical class 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 239000006227 byproduct Substances 0.000 description 8
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- -1 CH2BrCl Chemical compound 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N iodoform Chemical compound IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 1
- 102100037328 Chitotriosidase-1 Human genes 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 101000879661 Homo sapiens Chitotriosidase-1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical compound C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 description 1
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- MXOSTENCGSDMRE-UHFFFAOYSA-N butyl-chloro-dimethylsilane Chemical compound CCCC[Si](C)(C)Cl MXOSTENCGSDMRE-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000012070 reactive reagent Substances 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Description
本発明はtert−ブチルジメチルシランと塩素と
をハロゲン化炭化水素の存在下に反応させること
を特徴とするtert−ブチルジメチルクロロシラン
の新規でかつ改良された製造方法に関するもので
ある。
現在、医薬品製造の分野では医薬品の合成の過
程で中間体中の活性水素をシリル化剤と反応させ
て保護基を作り、目的の反応が行われた後に加水
分解してこの保護基を除去するという方法が広く
利用されている。そして、このシリル化剤として
はバルキーな基をもつているtert−ブチルジメチ
ルクロロシランが核酸合成、プロスタグランデイ
ン合成、チエナマイシン合成などに数多く用いら
れてその有用性が認められており、このものは立
体選択性が高く、かつシリル化生成物が高反応性
試薬に対して比較的安定であり、また、湿気や中
性水溶性中ではほとんど加水分解を受けず、した
がつて取り扱いも容易であるという利点を有して
いる。さらに強い酸性条件下や非水溶媒中ではフ
ツ素アニオンF-によつて選択的にはずすことが
できるという利点をもつている。
従来tert−ブチルジメチルクロロシランの合成
方法としてtert−ブチルジメチルシランに塩素ガ
スを反応させてtert−ブチルジメチルクロロシラ
ンを合成するには、安定性の面から溶媒として４
塩化炭素を使用していたがtert−ブチルジメチル
シランのtert−ブチル基及びメチル基の塩素化が
同時に起りたとえば
などの副生成物の生成がおこり、これらの化合物
は、沸点が目的とするtert−ブチルジメチルクロ
ロシランに極めて近く蒸留塔を用いての精留によ
つても分離が難しく高純度の製品が得られないと
いう問題があつた。
しかし本発明においては、tert−ブチルジメチ
ルシランと塩素とを反応させることによりtert−
ブチルジメチルクロロシランを製造するに際して
ハロゲン化炭化水素の共存下で行えば副生成物の
生成がほとんどおこらないことを見出した。
本発明で利用できるハロゲン化炭化水素として
は
CHBrCl2 CHBr2Cl、CHBr3、
CHCl3、CHI3、CH2BrCl、
CH2Br2、CH2ClI、CH2Cl2、
CH2I2、CH3I、
C2HCl5、CBrF2CH2Br、
CHBr2CHBr2、CCl3CH2Cl、CF3CHI2、
CCl3CH3、CHCl2H2Cl、
CH2BrCH2Cl、CH2BrCH2Br、CHCl2CH3、
CH2ClCH2Cl、CH2ICH2I、CH2BrCH3、
CH2ICH3、CH3CH2Cl、
CCl3CCl2CHCl2、CH2ClCHClCH2Cl、
CH2BrCH2CH2Cl、CH2ClCHBrCH3、
CH2BrCHBrCH3、CH2BrCH2CH2Br、
CH3CBr2CH3、CH2ClCH2CH2I、
CH2ClCHClCH3、CH2ClCH2CH2Cl、
CH3CCl2CH3、CH2ICH2CH2I、
CH2BrCH2CH2、CH3CHBrCH3、
CH2ClCH2CH3、CH3CHClCH3、
CH2ICH2CH3、CH3CHICH3、
CH3CH2CH2CH2Cl、CH3CH2CHClCH3、
CH3CH2CH2CH2Br、CH3CH2CHBrCH3、
The present invention relates to a new and improved method for producing tert-butyldimethylchlorosilane, which comprises reacting tert-butyldimethylsilane and chlorine in the presence of a halogenated hydrocarbon. Currently, in the field of pharmaceutical manufacturing, active hydrogen in an intermediate is reacted with a silylating agent to create a protective group during the pharmaceutical synthesis process, and after the desired reaction has taken place, this protective group is removed by hydrolysis. This method is widely used. As this silylating agent, tert-butyldimethylchlorosilane, which has a bulky group, is widely used in nucleic acid synthesis, prostaglandin synthesis, thienamycin synthesis, etc., and its usefulness has been recognized. It has high selectivity, the silylation product is relatively stable against highly reactive reagents, and it hardly undergoes hydrolysis in humid or neutral aqueous environments, so it is easy to handle. It has advantages. Furthermore, it has the advantage that it can be selectively removed by the fluorine anion F - under strongly acidic conditions or in non-aqueous solvents. Conventional methods for synthesizing tert-butyldimethylchlorosilane include reacting tert-butyldimethylsilane with chlorine gas to synthesize tert-butyldimethylchlorosilane.
Although carbon chloride was used, the tert-butyl and methyl groups of tert-butyldimethylsilane were simultaneously chlorinated, for example. The boiling point of these compounds is very close to that of the target tert-butyldimethylchlorosilane, and it is difficult to separate them even by rectification using a distillation column, making it difficult to obtain a high-purity product. There was a problem that there was no. However, in the present invention, by reacting tert-butyldimethylsilane with chlorine, tert-
It has been found that when butyldimethylchlorosilane is produced in the coexistence of halogenated hydrocarbons, almost no by-products are produced. Halogenated hydrocarbons that can be used in the present invention include CHBrCl2CHBr2Cl , CHBr3 , CHCl3, CHI3 , CH2BrCl , CH2Br2 , CH2ClI , CH2Cl2 , CH2I2 , CH 3 I , C2HCl5 , CBrF2CH2Br , CHBr2CHBr2 , CCl3CH2Cl , CF3CHI2 , CCl3CH3 , CHCl2H2Cl , CH2BrCH2Cl , CH2BrCH 2 Br, CHCl 2 CH 3 , CH 2 ClCH 2 Cl, CH 2 ICH 2 I, CH 2 BrCH 3 , CH 2 ICH 3 , CH 3 CH 2 Cl, CCl 3 CCl 2 CHCl 2 , CH 2 ClCHClCH 2 Cl, CH 2 BrCH 2 CH 2 Cl, CH 2 ClCHBrCH 3 , CH 2 BrCHBrCH 3 , CH 2 BrCH 2 CH 2 Br, CH 3 CBr 2 CH 3 , CH 2 ClCH 2 CH 2 I, CH 2 ClCHClCH 3 , CH 2 ClCH 2 CH 2 Cl, CH 3 CCl 2 CH 3 , CH 2 ICH 2 CH 2 I, CH 2 BrCH 2 CH 2 , CH 3 CHBrCH 3 , CH 2 ClCH 2 CH 3 , CH 3 CHClCH 3 , CH 2 ICH 2 CH 3 , CH 3 CHICH 3 , CH 3 CH 2 CH 2 CH 2 Cl, CH 3 CH 2 CHClCH 3 , CH 3 CH 2 CH 2 CH 2 Br, CH 3 CH 2 CHBrCH 3 ,
【式】【formula】
【式】【formula】
【式】
などが例示される。
ハロゲン化炭化水素の共存下でtert−ブチルジ
メチルシランに塩素ガスを反応させれば副生成物
の生成も殆どなく、目的とするtert−ブチルジメ
チルクロロシランが収率よく合成できる機構は明
確ではないが副生成物の生起を防止できる原因の
一つは溶媒として使用する当該ハロゲン化炭化水
素の分子中に存在する。Ｃ−Ｈ基がtert−ブチル
ジメチルシリル基を持つＣ−Ｈ基を塩素の攻撃か
ら保護する作用を有するものと考えられる。
使用するハロゲン化炭化水素の量は多ければ多
いほどよく、副生成物の生成を防止するが、必要
以上の添加は経済的ではないので、使用量は使用
する原料のtert−ブチルジメチルシランに対して
0.1〜100倍（重量）、好ましくは0.5〜10倍（重
量）である。反応温度は−70〜50℃、好ましくは
−30〜30℃の温度範囲がよく、この温度範囲で
tert−ブチルジメチルシランに塩素を当量（モ
ル）以上1.5倍当量（モル）以下反応させれば副
生成物の発生することもなく目的とするtert−ブ
チルジメチルクロロシランは反応終了後、ハロゲ
ン化炭化水素を留去したのち、残留分を蒸留精製
すれば純度99％以上のものとして定量的に合成で
きる。
次に本発明の実施例を挙げる。
実施例 １
tert−ブチルジメチルシラン116g（1.00モル）、
とジクロロメタン150gの混合物の中に塩素ガス
70g（1.00モル）を温度０℃にて２時間かけて吹き
込み反応させた、反応終了後ジクロロメタンを常
圧にて加熱し留去した後残留物を蒸留塔を用いて
精製し、沸点124〜125℃でtert−ブチルジメチル
クロロシラン149gを得た。このとき
等の副生成物の発生はおこつていなかつた。
比較例 １
実施例１に於てジクロロメタンの替りに四塩化
炭素150gを用いて、同様の条件下で実験を行な
つた処、tert−ブチルジメチルクロロシランは得
られたが次の副生成物が次の割合で含されてい
た。
〔Ａ〕……1.0％
〔Ｂ〕……1.2％
〔Ｃ〕……1.8％
実施例 ２〜15
tert−ブチルジメチルシラン116g（1.00モル）
と塩素ガスとを第１表に記載した条件で反応さ
せ、その後に使用したハロゲン化炭化水素の溶媒
を留去し、実施例１と同様に沸点124〜125℃の
tert−ブチルジメチルクロロシランを第１表に示
す収率で得た。
この実施例からも当該溶媒を使用した場合、全
く副生成物の〔Ａ〕、〔Ｂ〕及び〔Ｃ〕が生成しな
いことが判る。Examples include [Formula]. If tert-butyldimethylsilane is reacted with chlorine gas in the coexistence of a halogenated hydrocarbon, almost no by-products will be produced, and the mechanism by which the desired tert-butyldimethylchlorosilane can be synthesized in good yield is not clear. One of the reasons why by-products can be prevented from forming is present in the molecules of the halogenated hydrocarbon used as a solvent. It is thought that the C--H group has the effect of protecting the C--H group having a tert-butyldimethylsilyl group from attack by chlorine. The larger the amount of halogenated hydrocarbon used, the better, to prevent the formation of by-products, but adding more than necessary is not economical, so the amount used should be determined based on the raw material tert-butyldimethylsilane used. hand
0.1 to 100 times (by weight), preferably 0.5 to 10 times (by weight). The reaction temperature is -70 to 50℃, preferably -30 to 30℃;
If tert-butyldimethylsilane is reacted with chlorine equivalent (mol) to 1.5 times equivalent (mol), no by-products will be generated, and the desired tert-butyldimethylchlorosilane will be converted into halogenated hydrocarbon after the reaction is completed. After distilling off the residue, it can be quantitatively synthesized with a purity of 99% or higher by distilling and purifying the residue. Next, examples of the present invention will be described. Example 1 tert-butyldimethylsilane 116g (1.00mol),
Chlorine gas in a mixture of and dichloromethane 150g
70 g (1.00 mol) was reacted by blowing over 2 hours at a temperature of 0°C. After the reaction was completed, dichloromethane was heated at normal pressure and distilled off. The residue was purified using a distillation column to obtain a boiling point of 124-125. 149 g of tert-butyldimethylchlorosilane was obtained. At this time No by-products such as these were generated. Comparative Example 1 When an experiment was conducted under the same conditions as in Example 1 using 150 g of carbon tetrachloride instead of dichloromethane, tert-butyldimethylchlorosilane was obtained, but the following by-products were obtained. It was included in the proportion of [A]...1.0% [B]...1.2% [C]...1.8% Examples 2 to 15 tert-butyldimethylsilane 116g (1.00 mol)
and chlorine gas under the conditions listed in Table 1, and then the solvent of the halogenated hydrocarbon used was distilled off.
Tert-butyldimethylchlorosilane was obtained in the yield shown in Table 1. It can be seen from this example that the by-products [A], [B] and [C] were not produced at all when the solvent was used.
【表】【table】
Claims (1)
ゲン化炭化水素の存在下に反応させることを特徴
とするtert−ブチルジメチルクロロシランの製造
方法。1. A method for producing tert-butyldimethylchlorosilane, which comprises reacting tert-butyldimethylsilane and chlorine in the presence of a halogenated hydrocarbon.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61201490A JPS6357592A (en) | 1986-08-29 | 1986-08-29 | Production of tert-butyldimethylchlorosilane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61201490A JPS6357592A (en) | 1986-08-29 | 1986-08-29 | Production of tert-butyldimethylchlorosilane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6357592A JPS6357592A (en) | 1988-03-12 |
| JPH034557B2 true JPH034557B2 (en) | 1991-01-23 |
Family
ID=16441922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61201490A Granted JPS6357592A (en) | 1986-08-29 | 1986-08-29 | Production of tert-butyldimethylchlorosilane |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6357592A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0686468B2 (en) * | 1988-11-26 | 1994-11-02 | 信越化学工業株式会社 | Method for producing chlorinated silicon compound |
| JPH02157286A (en) * | 1988-12-09 | 1990-06-18 | Shin Etsu Chem Co Ltd | Production of chlorinated silicon compound |
| JP7143819B2 (en) * | 2019-06-05 | 2022-09-29 | 信越化学工業株式会社 | Organosilane compound having bulky substituents and method for producing the same |
-
1986
- 1986-08-29 JP JP61201490A patent/JPS6357592A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6357592A (en) | 1988-03-12 |
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