JPS6317049B2 - - Google Patents
Info
- Publication number
- JPS6317049B2 JPS6317049B2 JP3278980A JP3278980A JPS6317049B2 JP S6317049 B2 JPS6317049 B2 JP S6317049B2 JP 3278980 A JP3278980 A JP 3278980A JP 3278980 A JP3278980 A JP 3278980A JP S6317049 B2 JPS6317049 B2 JP S6317049B2
- Authority
- JP
- Japan
- Prior art keywords
- carbonate
- formula
- lower alkyl
- methoxyvinyl
- alkoxyvinyl
- 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
- -1 carbonate compound Chemical class 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 6
- 229910052753 mercury Inorganic materials 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 21
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- CXHHBNMLPJOKQD-UHFFFAOYSA-N methyl hydrogen carbonate Chemical compound COC(O)=O CXHHBNMLPJOKQD-UHFFFAOYSA-N 0.000 description 3
- 239000012038 nucleophile Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- AOGYCOYQMAVAFD-UHFFFAOYSA-M carbonochloridate Chemical compound [O-]C(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-M 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000002085 enols Chemical group 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- QIIPQYDSKRYMFG-UHFFFAOYSA-N phenyl hydrogen carbonate Chemical compound OC(=O)OC1=CC=CC=C1 QIIPQYDSKRYMFG-UHFFFAOYSA-N 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- ZXWHANCSQZVZCM-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;methanol Chemical compound OC.OC(=O)CC(O)(C(O)=O)CC(O)=O ZXWHANCSQZVZCM-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- CKBMGYQOKAYKFI-UHFFFAOYSA-N [N-]=[N+]=[N-].OC(O)=O Chemical compound [N-]=[N+]=[N-].OC(O)=O CKBMGYQOKAYKFI-UHFFFAOYSA-N 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- ZXHJTCXPSYCIKK-UHFFFAOYSA-N bis(2-methoxy-2-oxoethyl)mercury Chemical compound COC(=O)C[Hg]CC(=O)OC ZXHJTCXPSYCIKK-UHFFFAOYSA-N 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は、α―アルコキシビニル炭酸エステル
化合物、その製造法並びにその化合物からなるカ
ルボアルコキシ及びカルボアリーロキシ化剤に関
するものである。
本発明に係るα―アルコキシビニル炭酸エステ
ル化合物〔）は新規物質であり、その独特の化
学的性質に起因してカルボアルコキシ及びカルボ
アリーロキシ化剤として極めて有用である。
従来、カルボアルコキシ及びカルボアリーロキ
シ化剤の代表的なものとしてクロル炭酸エステ
ル、アジド炭酸エステル、ジアルキルカーボネイ
トが知られているが、これらはいずれも欠点を有
し、クロル炭酸エステルやジアルキルカーボネイ
トを用いるカルボアルコキシ及びカルボアリーロ
キシ化反応は反応の際、通常は塩基の存在が必要
であり、その為に無機塩やアミン塩酸塩等の副生
物を生成し、アジド炭酸エステルを用いる反応
は、アジド炭酸エステル類が極めて不安定で爆発
性を有する等反応上の制約を受ける上、これらを
用いる反応は一般に副反応が多発したり、反応条
件が緩和ではなく、収率も低い等の欠点を有して
いる。
本発明者らは、これら欠点を解消するものとし
て、イソプロペニル炭酸エステル化合物を、先
に、報告し、特許出願している（特願昭54−
022003号（特公昭62−6541号））。
このイソプロペニル炭酸エステル化合物を用い
るカルボアルコキシ及びカルボアリーロキシ化反
応は、エノール型がケト型に変換し易い性質を反
応の推進力とするものであり、比較的緩和な条件
下即ち例えばアミン類を反応させる場合は通常50
〜70℃で数時間〜一夜反応させることにより、相
当するカルボアルコキシ及びカルボアリーロキシ
化体を収率良く与え、副生物はアセトンのみであ
るという特徴ある反応となるのであるが、求核性
が弱いアミン類を反応させる場合は触媒例えばｐ
―トルエンスルホン酸等の酸が必要であつたり、
反応し難い等の欠点を残した。
本発明者らは、上記欠点に鑑み鋭意研究の結
果、一般式
（式中、Ｒは低級アルキル基を表わし、R′は
低級アルキル基又はフエニル基を表わす。）で示
されるα―アルコキシビニル炭酸エステル化合物
をカルボアルコキシ及びカルボアリーロキシ化剤
として用いる場合は、イソプロペニル炭酸エステ
ル化合物を用いる場合と比較して特に反応性の点
で格段に優れることを見出だし、本発明を完成す
るに至つた。
また、本発明に係るα―アルコキシビニル炭酸
エステル化合物〔〕は、ビス（カルボアルコキ
シメチル）水銀〔〕とハロホルメイト〔〕と
を反応させることにより、容易に製造することが
できる。
即ち、本発明は、一般式
（式中、Ｒは低級アルキル基を表わし、R′は
低級アルキル基又はフエニル基を表わす。）で示
されるα―アルコキシビニル炭酸エステル化合
物、一般式
（式中、Ｒは低級アルキル基を表わす。）で示
されるビス（カルボアルコキシメチル）水銀と一
般式
（式中、R′は低級アルキル基又はフエニル基
を表わし、Ｘはハロゲン原子を表わす。）で示さ
れるハロホルメイトとを反応させることを特徴と
するα―アルコキシビニル炭酸エステル化合物
〔〕の製造方法及びα―アルコキシビニル炭酸
エステル化合物〔〕からなるカルボアルコキシ
及びカルボアリーロキシ化剤である。
本発明に係るα―アルコキシビニル炭酸エステ
ル化合物〔〕からなるカルボアルコキシ及びカ
ルボアリーロキシ化剤は、その有するα―アルコ
キシビニル炭酸エステル構造に起因して反応性が
極めて高く、これを用いるカルボアルコキシ及び
カルボアリーロキシ化反応は、酸、塩基又は触媒
の存在無しの中性又は中性に近い緩和な条件下に
於ても極めて温和な温度で通常は極めて短時間の
うちに完全に定量的に進行し、求核性の弱いアミ
ン類であつてもこれを容易に反応させることがで
きるばかりでなく、酢酸エステルが唯一の副生物
であるので反応終了後のカルボアルコキシ及びカ
ルボアリーロキシ化体の単離は全く簡単である。
本発明に係るα―アルコキシビニル炭酸エステ
ル化合物〔〕を用いるアミン類その他の求核剤
のカルボアルコキシ及びカルボアリーロキシ化反
応を反応式で示すと次のとおりであり、反応はα
―アルコキシビニル炭酸エステル化合物〔〕の
カルボニル炭素に対する求核剤（SNで表わす。）
の攻撃によつて開始するものと考えられ、例えば
次式に従い、エノール・ケト変換反応が反応の推
進力となり反応が容易に進行する。
このように、本発明に係るα―アルコキシビニ
ル炭酸エステル化合物〔〕は、特に求核剤との
反応性に於て著しく優れるため、合成化学上種々
の有用な用途をもつ化合物となる。
即ち、例えば、アミノ基、イミノ基等の活性水
素を有する酸性基を保護する目的で、天然有機化
合物や医薬品等のＮ―炭酸エステル化に用いるこ
とができるとか、又はペプチド合成時に繁用され
るＮ―炭酸エステル化によつてアミノ基やイミノ
基等を容易に保護することができるアミノ保護剤
として用いるなどの広汎な応用分野がある。
本発明に係るα―アルコキシビニル炭酸エステ
ル化合物〔〕の例を挙げると、次のとおりであ
る。
(1) α―メトキシビニル炭酸エチルエステル
(2) α―メトキシビニル炭酸メチルエステル
(3) α―メトキシビニル炭酸フエニルエステル
これらのα―アルコキシビニル炭酸エステル化
合物〔〕は、ビス（カルボアルコキシメチル）
水銀〔〕とハロホルメイト〔〕とを、通常は
溶媒例えばベンゼン等の有機溶媒の存在下に、反
応させて製造する。
以下に実施例を述べ、本発明を更に詳細に説明
する。
α―メトキシビニル炭酸エチルエステル〔〕
ａは、酢酸メチルのエノレート等価物であるビス
（カルボメトキシメチル）水銀〔〕ａとアルキ
ル又はアリールクロロホルメート〔〕Aとの反応
で製造することができる。
典型的製造方法を、ビス（カルボメトキシメチ
ル）水銀〔〕ａとクロロホルメート〔〕Aとを
ベンゼン中で反応させてα―メトキシビニル炭酸
エチルエステル〔〕ａを製造する方法について
例示すると、次のとおりである。
エチルクロロホルメート（0.5mol）を、撹拌
下、予め加温したビス（カルボメトキシメチル）
水銀〔〕ａ（0.1mol）の乾燥ベンゼン（50ml）
溶液に、80℃で、１時間かけて、滴下後、同温度
で２日間撹拌する。ベンゼンを留去後、残液をｎ
―ペンタン（250ml）で抽出し、抽出液を濃縮、
蒸留し、無色の液体としてα―メトキシビニル炭
酸エチルエステル〔〕ａを43％の収率で得る。
〔α―メトキシビニル炭酸エチルエステル〔〕
ａ；R′＝C2H5、b.p.88−90゜／26mmＨｇ、IRν1765
及び1675cm-1、NMRδ1.33（ｔ，3H，CH2CH3）、
3.63（ｓ，3H，OCH3）、3.72（ｄ，1H，CH＝）、
3.92（ｄ，1H，CH＝）、及び4.23（ｑ，2H，
OCH2）〕Mass ｍ／e146（M+）。同様にして、他
のα―メトキシビニル炭酸メチル及びフエニルエ
ステル（〔〕ｂ及び〔〕ｃ）を製造した。〔α
―メトキシビニル炭酸メチルエステル〔〕ｂ：
R′＝CH3，b.p.75−76゜／35mmＨｇ，IRν1775及び
1680cm-1、NMRδ3.63（ｓ，3H，OCH3）、3.74
（ｄ，1H，CH＝）、3.80（ｓ，3H，OCH3）Mass
ｍ／e132（M+）、及び3.92（ｄ，1H，CH＝）；α
―メトキシビニル炭酸フエニルエステル〔〕
ｃ；R′＝C6H5，b.p.41゜／0.06mmＨｇ、IRν1775及
び1670cm-1、NMRδ3.68（ｓ，3H，OCH3）、3.82
（ｄ，1H，CH＝）、4.07（ｄ，1H，CH＝）、及び
7.15−7.45（ｍ，5H，ArH）〕Mass ｍ／e194
（M+）。α―メトキシビニル炭酸エチルエステル
〔〕ａとアミンとの反応は、おだやかな条件で
短時間のうちに（０〜60℃で１分間〜３時間）完
全に進行し、それに伴なつて揮発性の酢酸メチル
（b.p.56.9゜）が脱離する。
反応は、一般に、アミンと当量のα―メトキシ
ビニル炭酸エチルエステル〔〕ａを用いて、塩
化メチレン又は四塩化炭素中で、行われる。しか
しながら、同じ条件では、芳香族アミンのような
弱アミンとα―メトキシビニル炭酸エチルエステ
ル〔〕ａとの反応は、その完結に長時間を要す
る。５倍近く過剰のα―メトキシビニル炭酸エチ
ルエステル〔〕ａを用いることによつて、反応
時間を短縮することができる。反応混合物を蒸発
すると、殆どの場合に、殆ど純粋に目的のＮ―カ
ルボエトキシアミンが得られ、これをミクロ蒸
留、再結晶又はカラムクロマトグラフイで精製す
る。
α―メトキシビニル炭酸エチルエステル〔〕
ａは種々のタイプのアミンと反応し、相当するＮ
―カルボエトキシ体を与える。α―メトキシビニ
ル炭酸エチルエステル〔〕ａをアミンと等モル
を用いるとき、ジアミノ化合物の場合は、選択的
Ｎ―モノカルボエトキシ化が起る。２倍もしくは
それ以上のα―メトキシビニル炭酸エチルエステ
ル〔〕ａを使用するとアミノ基を両方共完全に
カルボエトキシ化することができる。他の官能基
の存在がアミンの選択的カルボエトキシ化反応に
与える制限については、ヒドロキシル基のような
弱塩基性基は妨害を引起さない。即ち、アミノア
ルコールはα―メトキシビニル炭酸エチルエステ
ル〔〕ａと容易に反応して相当するＮ―カルボ
エトキシ化体のみを高収率で与える。又、アミノ
酸と〔〕との反応は極めて緩和な条件下でも反
応が進行し、定量的に相当するＮ―カルボアルコ
キシ及びアリーロキシ化体を与える。
即ち、メタノール中又は水中、α―メトキシビ
ニル炭酸エチルエステル〔〕a1mmole，Ｌ―
フエニルアラニン1mmole、トリエチルアミン
1.5mmoleを室温下混合撹拌することにより、約
３時間で反応が終結する。反応（混合）液を５％
クエン酸メタノール溶液で酸性にし、クロロホル
ムで抽出し、クロロホルム溶液を減圧留去するこ
とにより、白色結晶が得られる。この白色結晶を
25％メタノール水溶液で再結晶精製することによ
り定量的にＮ―カルボエトキシ―Ｌ―フエニルア
ラニンが得られる。結果を要約して表に示す。
なお、α―メトキシビニル炭酸エチルエステル
〔〕ａと反応させるアミンがアミノアルコール
である場合において、触媒として酸例えばｐ―ト
ルエンスルホン酸が存在するときは相当するＮ―
カルボエトキシ―Ｏ―アセチル体が一挙に得ら
れ、このような触媒が存在しないときはＯ―アセ
チル化は起らず選択的にＮ―モノカルボエトキシ
化体が得られる。
The present invention relates to an α-alkoxyvinyl carbonate compound, a method for producing the same, and a carbalkoxy and carboaryloxylating agent comprising the compound. The α-alkoxyvinyl carbonate compound () according to the present invention is a new substance and is extremely useful as a carbalkoxy and carboaryloxylating agent due to its unique chemical properties. Conventionally, chlorocarbonate, azide carbonate, and dialkyl carbonate have been known as typical carbalkoxy and carboaryloxylating agents, but all of these have drawbacks, and chlorocarbonate and dialkyl carbonate are used. Carboalkoxy and carboaryloxylation reactions usually require the presence of a base and therefore produce by-products such as inorganic salts and amine hydrochlorides. In addition to being subject to reaction constraints such as esters being extremely unstable and explosive, reactions using these generally have drawbacks such as frequent side reactions, unrelaxed reaction conditions, and low yields. ing. The present inventors previously reported and filed a patent application for an isopropenyl carbonate compound as a solution to these drawbacks (Japanese Patent Application No.
No. 022003 (Special Publication No. 62-6541)). The carbalkoxy and carboaryloxylation reaction using this isopropenyl carbonate compound uses the property that the enol form is easily converted to the keto form as the driving force for the reaction, and is carried out under relatively mild conditions, for example, when amines are used. Usually 50 when reacting
By reacting at ~70°C for several hours to overnight, the corresponding carbalkoxy and carboaryloxylated products are obtained in good yields, and the only by-product is acetone. When reacting weak amines, a catalyst such as p
- An acid such as toluenesulfonic acid is required, or
It left some drawbacks such as difficulty in reacting. In view of the above-mentioned drawbacks, the present inventors have conducted extensive research, and as a result, the general formula (In the formula, R represents a lower alkyl group, R' represents a lower alkyl group or a phenyl group.) When using the α-alkoxyvinyl carbonate compound as a carbalkoxy and carboaryloxylating agent, The present inventors have discovered that the method is significantly superior in terms of reactivity, especially when compared to the case of using a propenyl carbonate compound, and have completed the present invention. Further, the α-alkoxyvinyl carbonate compound [ ] according to the present invention can be easily produced by reacting bis(carbalkoxymethyl)mercury [ ] and haloformate [ ]. That is, the present invention provides the general formula (In the formula, R represents a lower alkyl group, and R' represents a lower alkyl group or a phenyl group.) An α-alkoxyvinyl carbonate compound represented by the general formula (In the formula, R represents a lower alkyl group.) Bis(carbalkoxymethyl)mercury and the general formula (In the formula, R' represents a lower alkyl group or a phenyl group, and X represents a halogen atom.) A method for producing an α-alkoxyvinyl carbonate compound [], which is characterized by reacting it with a haloformate represented by the following formula: This is a carbalkoxy and carboaryloxylating agent consisting of an α-alkoxyvinyl carbonate compound []. The carbalkoxy and carboaryloxylating agent comprising the α-alkoxyvinyl carbonate compound [] according to the present invention has extremely high reactivity due to its α-alkoxyvinyl carbonate structure. Carboaryloxylation reactions usually proceed completely quantitatively in a very short time at very mild temperatures even under neutral or near-neutral mild conditions in the absence of acids, bases, or catalysts. However, not only can even weakly nucleophilic amines be easily reacted, but since acetic acid ester is the only by-product, the carbalkoxy and carboaryloxy compounds can be easily reacted after the reaction is completed. The separation is quite simple. The reaction formula for carboalkoxy and carboaryloxylation reactions of amines and other nucleophiles using the α-alkoxyvinyl carbonate compound [ ] according to the present invention is as follows, and the reaction is α
- Nucleophile for carbonyl carbon of alkoxyvinyl carbonate compound [] (represented by S N )
For example, according to the following formula, the enol/keto conversion reaction becomes the driving force for the reaction, and the reaction proceeds easily. As described above, the α-alkoxyvinyl carbonate compound [ ] according to the present invention is particularly excellent in reactivity with nucleophiles, and thus becomes a compound that has various useful uses in synthetic chemistry. That is, for example, it can be used for N-carbonate esterification of natural organic compounds and pharmaceuticals, etc., for the purpose of protecting acidic groups with active hydrogen such as amino groups and imino groups, or it is often used during peptide synthesis. It has a wide range of applications, including use as an amino-protecting agent that can easily protect amino groups, imino groups, etc. through N-carbonate esterification. Examples of the α-alkoxyvinyl carbonate compound [] according to the present invention are as follows. (1) α-Methoxyvinyl carbonate ethyl ester (2) α-Methoxyvinyl carbonate methyl ester (3) α-Methoxyvinyl carbonate phenyl ester These α-alkoxyvinyl carbonate compounds [] are bis(carbalkoxymethyl)
It is produced by reacting mercury [ ] and haloformate [ ], usually in the presence of a solvent such as an organic solvent such as benzene. EXAMPLES The present invention will be explained in more detail with reference to Examples below. α-Methoxyvinyl carbonate ethyl ester []
a can be produced by reacting bis(carbomethoxymethyl)mercury []a, which is an enolate equivalent of methyl acetate, with an alkyl or aryl chloroformate [] A . A typical production method for producing α-methoxyvinyl carbonate ethyl ester []a by reacting bis(carbomethoxymethyl)mercury[]a and chloroformate[] A in benzene is as follows. It is as follows. Ethyl chloroformate (0.5 mol) was mixed with pre-warmed bis(carbomethoxymethyl) under stirring.
Mercury []a (0.1mol) in dry benzene (50ml)
The mixture was added dropwise to the solution at 80° C. over 1 hour, and then stirred at the same temperature for 2 days. After distilling off the benzene, the remaining liquid was
-Extract with pentane (250ml), concentrate the extract,
Distillation yields α-methoxyvinyl carbonate ethyl ester []a as a colorless liquid with a yield of 43%.
[α-Methoxyvinyl carbonate ethyl ester]
a; R′=C 2 H 5 , bp88−90°/26mmHg, IRν1765
and 1675 cm -1 , NMR δ1.33 (t, 3H, CH 2 CH 3 ),
3.63 (s, 3H, OCH 3 ), 3.72 (d, 1H, CH=),
3.92 (d, 1H, CH=), and 4.23 (q, 2H,
OCH 2 )〕Mass m/e146 (M + ). Other α-methoxyvinyl methyl carbonate and phenyl esters ([]b and []c) were produced in the same manner. [α
-Methoxyvinyl carbonate methyl ester []b:
R′=CH 3 , bp75−76°/35mmHg, IRν1775 and
1680cm -1 , NMRδ3.63 (s, 3H, OCH 3 ), 3.74
(d, 1H, CH=), 3.80 (s, 3H, OCH 3 ) Mass
m/e132 (M + ), and 3.92 (d, 1H, CH=); α
-Methoxyvinyl carbonate phenyl ester []
c; R′=C 6 H 5 , bp41°/0.06mmHg, IRν1775 and 1670cm -1 , NMRδ3.68 (s, 3H, OCH 3 ), 3.82
(d, 1H, CH=), 4.07 (d, 1H, CH=), and
7.15−7.45 (m, 5H, ArH)〕Mass m/e194
(M + ). The reaction between α-methoxyvinyl carbonate ethyl ester []a and the amine proceeds completely in a short period of time (at 0 to 60°C for 1 minute to 3 hours) under mild conditions, and is accompanied by the reaction of volatile Methyl acetate (bp56.9°) is eliminated. The reaction is generally carried out in methylene chloride or carbon tetrachloride using an amine and an equivalent amount of α-methoxyvinyl carbonate ethyl ester []a. However, under the same conditions, the reaction between a weak amine such as an aromatic amine and α-methoxyvinyl carbonate ethyl ester []a takes a long time to complete. By using a nearly 5-fold excess of α-methoxyvinyl carbonate ethyl ester []a, the reaction time can be shortened. Evaporation of the reaction mixture gives in most cases almost pure the desired N-carboethoxyamine, which is purified by microdistillation, recrystallization or column chromatography. α-Methoxyvinyl carbonate ethyl ester []
a reacts with various types of amines and the corresponding N
-Gives carboethoxy form. When α-methoxyvinyl carbonate ethyl ester []a is used in an equimolar amount with the amine, selective N-monocarboethoxylation occurs in the case of a diamino compound. When twice or more of α-methoxyvinyl carbonate ethyl ester []a is used, both amino groups can be completely carbethoxylated. Regarding the limitations that the presence of other functional groups imposes on selective carboethoxylation reactions of amines, weakly basic groups such as hydroxyl groups do not cause any interference. That is, amino alcohol easily reacts with α-methoxyvinyl carbonate ethyl ester []a to give only the corresponding N-carboethoxylated product in high yield. Furthermore, the reaction between the amino acid and [] proceeds even under extremely mild conditions, and gives quantitatively equivalent N-carbalkoxy and aryloxylated products. That is, in methanol or water, α-methoxyvinyl carbonate ethyl ester []a1mmole, L-
Phenylalanine 1mmole, triethylamine
By mixing and stirring 1.5 mmole at room temperature, the reaction is completed in about 3 hours. 5% reaction (mixture) liquid
White crystals are obtained by acidifying with citric acid methanol solution, extraction with chloroform, and distilling off the chloroform solution under reduced pressure. This white crystal
N-carboethoxy-L-phenylalanine can be obtained quantitatively by recrystallization and purification with a 25% aqueous methanol solution. The results are summarized in the table. In addition, when the amine to be reacted with α-methoxyvinyl carbonate ethyl ester []a is an amino alcohol, when an acid such as p-toluenesulfonic acid is present as a catalyst, the corresponding N-
Carboethoxy-O-acetyl compounds are obtained all at once, and in the absence of such a catalyst, O-acetylation does not occur and N-monocarboethoxylated compounds are selectively obtained.
【表】【table】
【表】【table】
Claims (1)
低級アルキル基又はフエニル基を表わす。）で示
されるα―アルコキシビニル炭酸エステル化合
物。 ２ 一般式 （式中、Ｒは低級アルキル基を表わす。）で示
されるビス（カルボアルコキシメチル）水銀と一
般式 （式中、R′は低級アルキル基又はフエニル基
を表わし、Ｘはハロゲン原子を表わす。）で示さ
れるハロホルメイトとを反応させることを特徴と
する一般式 （式中、Ｒは低級アルキル基を表わし、R′は
低級アルキル基又はフエニル基を表わす。）で示
されるα―アルコキシビニル炭酸エステル化合物
の製造方法。 ３ 一般式 （式中、Ｒは低級アルキル基を表わし、R′は
低級アルキル基又はフエニル基を表わす。）で示
されるα―アルコキシビニル炭酸エステル化合物
からなるカルボアルコキシ及びカルボアリーロキ
シ化剤。[Claims] 1. General formula (In the formula, R represents a lower alkyl group, and R' represents a lower alkyl group or a phenyl group.) An α-alkoxyvinyl carbonate compound represented by the formula: 2 General formula (In the formula, R represents a lower alkyl group.) Bis(carbalkoxymethyl)mercury and the general formula (In the formula, R' represents a lower alkyl group or phenyl group, and X represents a halogen atom.) (In the formula, R represents a lower alkyl group, and R' represents a lower alkyl group or a phenyl group.) A method for producing an α-alkoxyvinyl carbonate compound represented by the formula. 3 General formula (In the formula, R represents a lower alkyl group, and R' represents a lower alkyl group or a phenyl group.) A carbalkoxy and carboaryloxylating agent comprising an α-alkoxyvinyl carbonate compound represented by the formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3278980A JPS56131549A (en) | 1980-03-17 | 1980-03-17 | Alpha-alkoxyvinyl carbonic acid ester compound, its preparation, and carboalkoxylating and carboaryloxylating agent composed thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3278980A JPS56131549A (en) | 1980-03-17 | 1980-03-17 | Alpha-alkoxyvinyl carbonic acid ester compound, its preparation, and carboalkoxylating and carboaryloxylating agent composed thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56131549A JPS56131549A (en) | 1981-10-15 |
| JPS6317049B2 true JPS6317049B2 (en) | 1988-04-12 |
Family
ID=12368609
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3278980A Granted JPS56131549A (en) | 1980-03-17 | 1980-03-17 | Alpha-alkoxyvinyl carbonic acid ester compound, its preparation, and carboalkoxylating and carboaryloxylating agent composed thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS56131549A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5182296A (en) * | 1989-10-26 | 1993-01-26 | Tanabe Seiyaky Co., Ltd. | Naphthyloxazolidone derivatives |
-
1980
- 1980-03-17 JP JP3278980A patent/JPS56131549A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56131549A (en) | 1981-10-15 |
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