JPS6364435B2 - - Google Patents
Info
- Publication number
- JPS6364435B2 JPS6364435B2 JP54070366A JP7036679A JPS6364435B2 JP S6364435 B2 JPS6364435 B2 JP S6364435B2 JP 54070366 A JP54070366 A JP 54070366A JP 7036679 A JP7036679 A JP 7036679A JP S6364435 B2 JPS6364435 B2 JP S6364435B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- multiplet
- diazabicyclo
- octane
- optically active
- 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
- 150000004795 grignard reagents Chemical class 0.000 claims description 11
- -1 magnesium halide Chemical class 0.000 claims description 11
- 239000007818 Grignard reagent Substances 0.000 claims description 10
- 150000007854 aminals Chemical class 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical class OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000011777 magnesium Substances 0.000 claims description 6
- 229910052749 magnesium Inorganic materials 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- IVRYBIASBRGJQI-UHFFFAOYSA-N methyl 2-phenyl-1,3,5,6,7,7a-hexahydropyrrolo[1,2-c]imidazole-3-carboxylate Chemical compound COC(=O)C1N2CCCC2CN1C1=CC=CC=C1 IVRYBIASBRGJQI-UHFFFAOYSA-N 0.000 description 3
- MCHWKJRTMPIHRA-NSHDSACASA-N n-[[(2s)-pyrrolidin-2-yl]methyl]aniline Chemical compound C([C@H]1NCCC1)NC1=CC=CC=C1 MCHWKJRTMPIHRA-NSHDSACASA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- IBLCBXMDPIZZOB-UHFFFAOYSA-N 2,3,3a,4,5,6-hexahydro-1h-pyrrolo[1,2-b]pyrazole Chemical compound C1CNN2CCCC21 IBLCBXMDPIZZOB-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical class O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- DJSCQCGHDWBAMG-VIFPVBQESA-N (2r)-2-hydroxy-2-phenylpropanal Chemical compound O=C[C@@](O)(C)C1=CC=CC=C1 DJSCQCGHDWBAMG-VIFPVBQESA-N 0.000 description 1
- BEYTUOFWMWNNTA-UHFFFAOYSA-N 1-(2-phenyl-1,3,5,6,7,7a-hexahydropyrrolo[1,2-c]imidazol-3-yl)ethanone Chemical compound CC(=O)C1N2CCCC2CN1C1=CC=CC=C1 BEYTUOFWMWNNTA-UHFFFAOYSA-N 0.000 description 1
- NFDXQGNDWIPXQL-UHFFFAOYSA-N 1-cyclooctyldiazocane Chemical class C1CCCCCCC1N1NCCCCCC1 NFDXQGNDWIPXQL-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- HTGNDXZAOJQEQK-UHFFFAOYSA-N 2-methyl-1-(2-phenyl-1,3,5,6,7,7a-hexahydropyrrolo[1,2-c]imidazol-3-yl)propan-1-one Chemical compound CC(C)C(=O)C1N2CCCC2CN1C1=CC=CC=C1 HTGNDXZAOJQEQK-UHFFFAOYSA-N 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000006058 4-methyl-4-pentenyl group Chemical group 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000004791 alkyl magnesium halides Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004792 aryl magnesium halides Chemical class 0.000 description 1
- FWTXWYXPXGKVJG-UHFFFAOYSA-N atrolactamide Chemical compound NC(=O)C(O)(C)C1=CC=CC=C1 FWTXWYXPXGKVJG-UHFFFAOYSA-N 0.000 description 1
- 229950011225 atrolactamide Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- XNLXZJSWGZWDMZ-UHFFFAOYSA-N ethyl 2-phenyl-1,3,5,6,7,7a-hexahydropyrrolo[1,2-c]imidazole-3-carboxylate Chemical compound CCOC(=O)C1N2CCCC2CN1C1=CC=CC=C1 XNLXZJSWGZWDMZ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical compound [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 description 1
- 229910001641 magnesium iodide Inorganic materials 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- RNVVYVPDHMKDTL-UHFFFAOYSA-N methyl 2-(hydroxymethoxy)acetate Chemical compound COC(=O)COCO RNVVYVPDHMKDTL-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- XYUQMENHCBNLPM-UHFFFAOYSA-N phenyl-(2-phenyl-1,3,5,6,7,7a-hexahydropyrrolo[1,2-c]imidazol-3-yl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1N2CCCC2CN1C1=CC=CC=C1 XYUQMENHCBNLPM-UHFFFAOYSA-N 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明はアミナール誘導体の製造法に関するも
のである。さらに詳しくは一般式(2)
（式中、Ａはアリール基、R2はアルキル基を
表わす。）
で示される光学活性もしくはラセミのグリオキシ
ル酸誘導体にグリニアル試薬を反応させることを
特徴とする一般式(3)
（式中、Ａはアリール基、R3はアルキル基、
アルケニル基、アルキニール基、アラルキル基、
アリール基を表わす。）
で示される光学活性もしくはラセミのアミナール
誘導体の製造法、および一般式(2)で示される光学
活性もしくはラセミのグリオキシル酸誘導体にハ
ロゲン化マグネシウムの存在下にグリニアル試薬
を反応させることを特徴とする一般式(3)で示され
る光学活性もしくはラセミのアミナール誘導体
（以後アミナールと略称する）の製造法に関する
ものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing aminal derivatives. For more details, see general formula (2) (In the formula, A represents an aryl group and R2 represents an alkyl group.) General formula (3) characterized by reacting an optically active or racemic glyoxylic acid derivative represented by the following with a Grignard reagent. (In the formula, A is an aryl group, R 3 is an alkyl group,
alkenyl group, alkynyl group, aralkyl group,
Represents an aryl group. ) A method for producing an optically active or racemic aminal derivative represented by formula (2), which is characterized by reacting an optically active or racemic glyoxylic acid derivative represented by general formula (2) with a Grignard reagent in the presence of a magnesium halide. This invention relates to a method for producing an optically active or racemic aminal derivative (hereinafter abbreviated as aminal) represented by general formula (3).
本発明の対象である一般式(3)に示されるアルキ
ルグリオキザール、アルケニルグリオキザール、
アルキニールグリオキザール、アラルキルグリオ
キザールのアミナールは新規化合物である。例示
すれば一般式(1)中のＡとしてフエニル基、２，６
―キシリジル基、ｐ―トリル基、ナフチル基等で
あり、R3はアルキル基として、メチル基、エチ
ル基、ｎ―プロピル基、イソプロピル基、ｎ―ブ
チル基、イソブチル基、ｎ―アミル基等を、アル
ケニル基として、２―プロペニル基、２―ブテニ
ル基、３―ブテニル基、２―ペンテニル基、３―
ペンテニル基、４―ペンテニル基、４―メチル―
４―ペンテニル基等を、アルキニール基として、
エチニル基、プロパルギル基、２―ブチニル基、
２―ペンチニル基、３―ペンチニル基等を、アラ
ルキル基としてベンジル基、フエネチル基、フエ
ニルプロピル基等を挙げることができる。これら
の化合物は農薬、医薬の中間原料となり得るもの
である。 Alkylglyoxal, alkenylglyoxal represented by general formula (3), which is the object of the present invention,
The aminals of alkynylglyoxal and aralkylglyoxal are new compounds. For example, A in general formula (1) is a phenyl group, 2,6
-xylidyl group, p-tolyl group, naphthyl group, etc., and R 3 is an alkyl group such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, n-amyl group, etc. , as the alkenyl group, 2-propenyl group, 2-butenyl group, 3-butenyl group, 2-pentenyl group, 3-
Pentenyl group, 4-pentenyl group, 4-methyl-
4-pentenyl group etc. as an alkynyl group,
ethynyl group, propargyl group, 2-butynyl group,
Examples of the aralkyl group include 2-pentynyl group and 3-pentynyl group, and examples of the aralkyl group include benzyl group, phenethyl group, and phenylpropyl group. These compounds can be used as intermediate raw materials for agricultural chemicals and medicines.
例えば参考例に掲げたごとく光学活性な置換グ
リオキザールのアミナールをグリニアル試薬と反
応させ、次いで加水分解することにより光学活性
α―ヒドロキシアルデヒドを高い光学収率で得る
ことができる。該アルデヒドを酸化してカルボン
酸とした後、アミド化することによりアトロラク
タミド系鎮痛剤に誘導し得る。 For example, as shown in Reference Examples, an optically active α-hydroxyaldehyde can be obtained in high optical yield by reacting the aminal of an optically active substituted glyoxal with a Grignard reagent and then hydrolyzing it. The aldehyde can be oxidized to a carboxylic acid and then amidated to produce an atrolactamide analgesic.
本発明において用いられる一般式(2)で示される
グリオキシル酸誘導体（ジアザビシクロオクタン
誘導体）は例えば参考例に掲げたごとく２―（Ｎ
置換アミノメチル）ピロリジンとグリオキシル酸
誘導体から製造することができ、参考例以外にも
例えば２―エトキシカルボニル―３―フエニル―
１，３―ジアザビシクロ〔3.3.0〕オクタン、２
―ブトキシカボニル―３―フエニル―１，３―ジ
アザビシクロ〔3.3.0〕オクタン等の２―アルコ
キシカルボニル―３―フエニル―１，３―ジアザ
ビシクロ〔3.3.0〕オクタンを例示することがで
きる。 The glyoxylic acid derivative (diazabicyclooctane derivative) represented by the general formula (2) used in the present invention is, for example, 2-(N
It can be produced from substituted aminomethyl)pyrrolidine and glyoxylic acid derivatives, and in addition to the reference examples, for example, 2-ethoxycarbonyl-3-phenyl-
1,3-Diazabicyclo[3.3.0]octane, 2
Examples include 2-alkoxycarbonyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane such as -butoxycarbonyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane.
光学活性もしくはラセミのグリオキシル酸誘導
体にグリニアル試薬を反応させることにより本発
明のアミナールが生成する。 The aminal of the present invention is produced by reacting an optically active or racemic glyoxylic acid derivative with a Grignard reagent.
本発明でいうグリニアル試薬とは、一般にいわ
れるグリニアル試薬、例えばアルキルマグネシウ
ムハライド、アルケニルマグネシウムハライド、
アルキニールマグネシウムハライド、アラルキル
マグネシウムハライド、アリールマグネシウムハ
ライド等の他これらの有機部分に官能基を含むよ
うなものでもよい。 The Grignard reagent referred to in the present invention refers to commonly-used Grignard reagents, such as alkylmagnesium halides, alkenylmagnesium halides,
In addition to alkynylmagnesium halides, aralkylmagnesium halides, arylmagnesium halides, etc., those containing functional groups in their organic moieties may also be used.
光学活性もしくはラセミのグリオキシル酸誘導
体にグリニアル試薬を反応させる際に、ハロゲン
化マグネシウムの存在下に行なうとアミナール誘
導体の収率を高めることができる。 When reacting an optically active or racemic glyoxylic acid derivative with a Grignard reagent, the yield of the aminal derivative can be increased if the reaction is carried out in the presence of magnesium halide.
本発明でいうハロゲン化マグネシウムとはヨウ
化マグネシウム、臭化マグネシウム、塩化マグネ
シウムであり、好ましくは塩化マグネシウムが用
いられる。グリニアル試薬を反応させる時に用い
る溶媒としてはエーテル、テトラヒドロフランも
しくはこれらを含む混合溶媒など通常のグリニア
ル反応に用いられる溶媒でよいがハロゲン化マグ
ネシウムの存在下にグリニアル試薬を反応させる
時はテトラヒドロフランの存在下で行なうことが
好ましい。反応温度は用いる溶媒の沸点以下で実
施することができる。副生物を少なくするために
は温度が低い方が望ましい。 The magnesium halide used in the present invention includes magnesium iodide, magnesium bromide, and magnesium chloride, and preferably magnesium chloride is used. The solvent used when reacting the Grignard reagent may be a solvent used in a normal Grignard reaction, such as ether, tetrahydrofuran, or a mixed solvent containing these. However, when reacting the Grignard reagent in the presence of magnesium halide, it is preferable to use it in the presence of tetrahydrofuran. It is preferable to do so. The reaction temperature can be lower than the boiling point of the solvent used. In order to reduce the amount of by-products, lower temperatures are desirable.
以下の実施例で発明の具体的な説明をする。 The invention will be specifically explained in the following examples.
実施例 １
２―カルボメトキシ―３―フエニル―１，３―
ジアザビシクロ〔3.3.0〕オクタン295mgを７mlの
THFに溶解し138mgの無水塩化マグネシウムを加
え10分間加熱還流した。−70℃に冷却し、メチル
マグネシウムブロミドのエーテル溶液を1.36倍当
量滴下した。−70℃で15分間撹拌後、飽和塩化ア
ンモニウム水溶液とエーテルを加え室温まで昇温
させた。エーテルで抽出後乾燥し、溶媒を減圧下
に留去した。油状残留物をアルミナカラムクロマ
トグラフイーで精製し199mg（72％）の２―アセ
チル―１，３―ジアザビシクロ〔3.3.0〕オクタ
ンを得た。Example 1 2-carbomethoxy-3-phenyl-1,3-
7ml of diazabicyclo[3.3.0]octane 295mg
138 mg of anhydrous magnesium chloride was dissolved in THF and heated under reflux for 10 minutes. The mixture was cooled to −70° C., and an ether solution of methylmagnesium bromide was added dropwise in an amount of 1.36 times. After stirring at -70°C for 15 minutes, a saturated aqueous ammonium chloride solution and ether were added and the mixture was heated to room temperature. After extraction with ether and drying, the solvent was distilled off under reduced pressure. The oily residue was purified by alumina column chromatography to obtain 199 mg (72%) of 2-acetyl-1,3-diazabicyclo[3.3.0]octane.
nmrピークはδ（ppm）＝1.5〜2.2（4H、マルチ
プレツト）、1.9（3H、シングレツト）、2.4〜3.3
（3H、マルチプレツト）、3.5〜3.9（2H、マルチプ
レツト）、4.1（1H、シングレツト）、6.1〜7.1
（5H、マルチプレツト）であつた。 nmr peaks are δ (ppm) = 1.5-2.2 (4H, multiplet), 1.9 (3H, singlet), 2.4-3.3
(3H, multiplet), 3.5 to 3.9 (2H, multiplet), 4.1 (1H, singlet), 6.1 to 7.1
(5H, multiplet).
実施例 ２
参考例に掲げたごとく1.76ｇの（Ｓ）―２―
（アニリノメチル）ピロリジンから製造した２―
カルボメトキシ―３―フエニル―１，３―ジアザ
ビシクロ〔3.3.0〕オクタンを50mlのTHFに溶解
し1.05ｇの無水塩化マグネシウムを加え10分間加
熱還流した。−70℃に冷却し、エチルマグネシウ
ムブロミドのエーテル溶液を1.46倍当量滴下し
た。以後実施例１と同様の操作を行ない694mg
（28％）の２―プロピオニル―３―フエニル―１，
３―ジアザビシクロ〔3.3.0）オクタンを得た。Example 2 As listed in the reference example, 1.76g of (S)-2-
2- produced from (anilinomethyl)pyrrolidine
Carbomethoxy-3-phenyl-1,3-diazabicyclo[3.3.0]octane was dissolved in 50 ml of THF, 1.05 g of anhydrous magnesium chloride was added, and the mixture was heated under reflux for 10 minutes. The mixture was cooled to −70° C., and an ether solution of ethylmagnesium bromide was added dropwise in an amount of 1.46 times. Thereafter, the same operation as in Example 1 was performed to obtain 694 mg.
(28%) of 2-propionyl-3-phenyl-1,
3-Diazabicyclo[3.3.0)octane was obtained.
nmrピークはδ（ppm）＝1.0（3H、トリプレツ
ト）、1.4〜2.1（4H、マルチプレツト）、2.1〜2.6
（2H、マルチプレツト）、2.6〜3.3（3H、マルチプ
レツト）、3.5〜3.9（2H、マルチプレツト）4.2
（1H、シングレツト）、6.1〜7.1（5H、マルチプレ
ツト）であつた。 nmr peaks are δ (ppm) = 1.0 (3H, triplet), 1.4-2.1 (4H, multiplet), 2.1-2.6
(2H, multiplet), 2.6 to 3.3 (3H, multiplet), 3.5 to 3.9 (2H, multiplet) 4.2
(1H, singlet), 6.1-7.1 (5H, multiplet).
実施例 ３
637mgの（Ｓ）―２―（アニリノメチル）ピロ
リジンから製造した２―カルボメトキシ―３―フ
エニル―１，３―ジアザビシクロ〔3.3.0〕オク
タンを18mlのTHFに溶解し、378mgの無水塩化マ
グネシウムを加え、10分間加熱還流した。−70℃
に冷却し、イソプロピルマグネシウムブロミドの
エーテル溶液を1.37倍当量滴下した。以後実施例
１と同様の操作を行ない731mg（79％）の２―イ
ソブチリル―３―フエニル―１，３―ジアザビシ
クロ〔3.3.0〕オクタンを得た。Example 3 2-carbomethoxy-3-phenyl-1,3-diazabicyclo[3.3.0]octane prepared from 637 mg of (S)-2-(anilinomethyl)pyrrolidine was dissolved in 18 ml of THF and 378 mg of anhydrous chloride was added. Magnesium was added and the mixture was heated under reflux for 10 minutes. −70℃
The mixture was cooled to 1.37 times the equivalent of an ether solution of isopropylmagnesium bromide was added dropwise. Thereafter, the same operation as in Example 1 was carried out to obtain 731 mg (79%) of 2-isobutyryl-3-phenyl-1,3-diazabicyclo[3.3.0]octane.
nmrピークはδ（ppm）＝0.9（3H、ダブレツ
ト）、1.1（3H、ダブレツト）、1.5〜2.2（4H、マル
チプレツト）、2.4〜3.3（4H、マルチプレツト）、
3.5〜3.9（2H、マルチプレツト）、4.4（1H、シン
グレツト）、6.2〜7.1（5H、マルチプレツト）であ
つた。 The nmr peaks are δ (ppm) = 0.9 (3H, doublet), 1.1 (3H, doublet), 1.5-2.2 (4H, multiplet), 2.4-3.3 (4H, multiplet),
They were 3.5-3.9 (2H, multiplet), 4.4 (1H, singlet), and 6.2-7.1 (5H, multiplet).
実施例 ４
181mgの（Ｓ）―２―（アニリノメチル）ピロ
リジンから製造した２―カルボメトキシ―３―フ
エニル―１，３―ジアザビシクロ〔3.3.0〕オク
タンを5.5mlのTHFに溶解し、108mgの無水塩化
マグネシウムを加え、10分間加熱還流した。−70
℃に冷却しフエニルマグネシウムブロミドのエー
テル溶液を1.38倍当量滴下した。−70℃で15分間
還流後、飽和塩化アンモニウム水溶液とエーテル
を加え室温まで昇温させた。エーテルで抽出後、
エーテル層を１規定の水酸化ナトリウム水溶液な
らびに飽和食塩水で洗浄後、乾燥し、溶媒を減圧
下に留去した。油状残留物をアルミナカラムクロ
マトグラフイーで精製し、230mg（77％）の２―
ベンゾイル―３―フエニル―１，３―ジアザビシ
クロ〔3.3.0〕オクタンを得た。Example 4 181 mg of 2-carbomethoxy-3-phenyl-1,3-diazabicyclo[3.3.0]octane prepared from (S)-2-(anilinomethyl)pyrrolidine was dissolved in 5.5 ml of THF and 108 mg of anhydrous Magnesium chloride was added and the mixture was heated under reflux for 10 minutes. −70
The mixture was cooled to ℃ and 1.38 equivalents of an ether solution of phenylmagnesium bromide was added dropwise. After refluxing at -70°C for 15 minutes, a saturated aqueous ammonium chloride solution and ether were added and the mixture was heated to room temperature. After extraction with ether,
The ether layer was washed with a 1N aqueous sodium hydroxide solution and saturated brine, dried, and the solvent was distilled off under reduced pressure. The oily residue was purified by alumina column chromatography and 230 mg (77%) of 2-
Benzoyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane was obtained.
nmrピークはδ（ppm）＝1.6〜2.2（4H、マルチ
プレツト）、2.4〜3.9（5H、マルチプレツト）、5.4
（1H、シングレツト）、6.1〜7.9（10H、マルチプ
レツト）であつた。 The nmr peaks are δ (ppm) = 1.6-2.2 (4H, multiplet), 2.4-3.9 (5H, multiplet), 5.4
(1H, singlet), 6.1-7.9 (10H, multiplet).
実施例 ５
２―カルボンメトキシ―３―フエニル―１，３
―ジアザビシクロ〔3.3.0〕オクタン99mgを５ml
のエーテルに溶解し、−70℃に冷却した。メチル
マグネシウムブロミドのエーテル溶液を1.2倍当
量滴下した。−70℃で1.5時間反応させた後、飽和
塩化アンモニウム水溶液を加え、室温まで昇温さ
せた。エーテル層を分離し、乾燥後、溶媒を減圧
下に留去した。nmrスペクトルの測定により２―
アセチル―３―フエニル―１，３―ジアザビシク
ロ〔3.3.0〕オクタンの収率は54％であつた。Example 5 2-Carbonmethoxy-3-phenyl-1,3
-Diazabicyclo[3.3.0]octane 99mg 5ml
of ether and cooled to -70°C. An ether solution of methylmagnesium bromide was added dropwise in an amount of 1.2 times. After reacting at −70° C. for 1.5 hours, a saturated aqueous ammonium chloride solution was added, and the temperature was raised to room temperature. After separating the ether layer and drying, the solvent was distilled off under reduced pressure. By measuring the nmr spectrum, 2-
The yield of acetyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane was 54%.
実施例 ６
720mgの２―カルボメトキシ―３―フエニル―
１，３―ジアザビシクロ〔3.3.0〕オクタンを25
mlのTHFに溶解し291mgの無水塩化マグネシウム
を加え10分間加熱還流した。−70℃に冷却し、４
―メチル―４―ペンテニルマグネシウムブロミド
のエーテル溶液1.6倍当量を滴下した。以後実施
例１と同様の操作を行ない378mg（44％）の２―
（5′―メチル―5′―ヘキセノイル）―３―フエニ
ル―１，３―ジアザビシクロ〔3.3.0〕オクタン
を得た。nmrピークはδ（ppm）＝1.6（3H、シン
グレツト）、1.5〜2.1（8H、マルチプレツト）2.2
〜2.5（2H、マルチプレツト）、2.6〜3.3（3H、マ
ルチプレツト）、3.5〜3.9（2H、マルチプレツト）、
4.2（1H、シングレツト）、4.5（2H、ブロードシン
グレツト）、6.2〜7.1（5H、マルチプレツト）であ
つた。Example 6 720 mg of 2-carbomethoxy-3-phenyl
1,3-diazabicyclo[3.3.0]octane 25
ml of THF, 291 mg of anhydrous magnesium chloride was added thereto, and the mixture was heated under reflux for 10 minutes. Cool to -70℃, 4
A 1.6-fold equivalent of an ether solution of -methyl-4-pentenylmagnesium bromide was added dropwise. Thereafter, the same operation as in Example 1 was performed to obtain 378 mg (44%) of 2-
(5'-Methyl-5'-hexenoyl)-3-phenyl-1,3-diazabicyclo[3.3.0]octane was obtained. nmr peaks are δ (ppm) = 1.6 (3H, singlet), 1.5-2.1 (8H, multiplet) 2.2
~2.5 (2H, multiplet), 2.6~3.3 (3H, multiplet), 3.5~3.9 (2H, multiplet),
They were 4.2 (1H, singlet), 4.5 (2H, broad singlet), and 6.2-7.1 (5H, multiplet).
参考例 １
（Ｓ）―２―（アニリノメチル）ピロリジン
1.76ｇとヒドロキシメトキシ酢酸メチル1.28ｇを
20mlのベンゼンに溶解し、共沸で水を除去しなが
ら30分間加熱還流した。減圧下溶媒を留去し2.46
ｇの２―カルボメトキシ―３―フエニル―１，３
―ジアザビシクロ〔3.3.0〕オクタンを得た。Reference example 1 (S)-2-(anilinomethyl)pyrrolidine
1.76g and 1.28g of methyl hydroxymethoxyacetate.
It was dissolved in 20 ml of benzene and heated under reflux for 30 minutes while removing water azeotropically. Distill the solvent under reduced pressure 2.46
g of 2-carbomethoxy-3-phenyl-1,3
- Obtained diazabicyclo [3.3.0] octane.
nmrピークはδ（ppm）＝1.5〜2.3（4H、マルチ
プレツト）、2.3〜4.1（5H、マルチプレツト）、3.5
（3H、シングレツト）、4.6（1H、シングレツト）、
6.2〜7.1（5H、マルチプレツト）であつた。 nmr peaks are δ (ppm) = 1.5-2.3 (4H, multiplet), 2.3-4.1 (5H, multiplet), 3.5
(3H, singlet), 4.6 (1H, singlet),
It was 6.2-7.1 (5H, multiplet).
参考例 ２
５―（Ｓ）―２―アセチル―３―フエニル―
１，３―ジアザビシクロ〔3.3.0〕オクタン258mg
をエーテル５mlに溶解し、−70℃に冷却し、フエ
ニルマグネシウムブロミドのエーテル溶液２倍当
量を加え１時間反応させた。飽和塩化アンモニウ
ム水溶液３mlを加え、室温まで昇温させた。エー
テル層を分離し、１規定水酸化ナトリウム水溶液
で洗浄後、２％塩酸11mlを加え、０℃で12時間反
応させた。エーテル層を分離し飽和食塩水で洗浄
後、芒硝で乾燥した。減圧下エーテルを留去し得
られた残留物をシリカゲルカラムで精製し128mg
（76％）の（Ｒ）―（―）―２―ヒドロキシ―２
―フエニルプロピオンアルデヒドを得た。〔α〕D
＝−225゜（Ｃ＝1.060、ベンゼン）で光学収率は99
％であつた。Reference example 2 5-(S)-2-acetyl-3-phenyl-
1,3-Diazabicyclo[3.3.0]octane 258mg
was dissolved in 5 ml of ether, cooled to -70°C, two equivalents of an ether solution of phenylmagnesium bromide were added, and the mixture was reacted for 1 hour. 3 ml of saturated ammonium chloride aqueous solution was added, and the temperature was raised to room temperature. The ether layer was separated, washed with 1N aqueous sodium hydroxide solution, 11 ml of 2% hydrochloric acid was added, and the mixture was reacted at 0°C for 12 hours. The ether layer was separated, washed with saturated brine, and dried over Glauber's salt. The ether was distilled off under reduced pressure, and the resulting residue was purified using a silica gel column to give 128 mg.
(76%) of (R)-(-)-2-hydroxy-2
-Phenylpropionaldehyde was obtained. [α] D
= -225° (C = 1.060, benzene) and the optical yield is 99
It was %.
Claims (1)
表わす） で示される光学活性もしくはラセミのグリオキシ
ル酸誘導体にグリニアル試薬を反応させることを
特徴とする一般式(3) （式中、Ａはアリール基、R3はアルキル基、
アルケニル基、アルキニール基、アラルキル基、
アリール基を表わす。） で示される光学活性もしくはラセミのアミナール
誘導体の製造法。 ２ 一般式(2) （式中、R2はアルキル基、Ａはアリール基を
表わす） で示される光学活性もしくはラセミのグリオキシ
ル酸誘導体にハロゲン化マグネシウムの存在下、
グリニアル試薬を反応させることを特徴とする一
般式(3) （式中、Ａはアリール基、R3はアルキル基、
アルケニル基、アルキニール基、アラルキル基、
アリール基を表わす。） で示される光学活性もしくはラセミのアミナール
誘導体の製造法。[Claims] 1 General formula (2) (In the formula, R 2 represents an alkyl group and A represents an aryl group) General formula (3) characterized by reacting a Grignard reagent with an optically active or racemic glyoxylic acid derivative represented by (In the formula, A is an aryl group, R 3 is an alkyl group,
alkenyl group, alkynyl group, aralkyl group,
Represents an aryl group. ) A method for producing an optically active or racemic aminal derivative. 2 General formula (2) (In the formula, R 2 represents an alkyl group and A represents an aryl group.) In the presence of magnesium halide, an optically active or racemic glyoxylic acid derivative represented by
General formula (3) characterized by reacting with a Grignard reagent (In the formula, A is an aryl group, R 3 is an alkyl group,
alkenyl group, alkynyl group, aralkyl group,
Represents an aryl group. ) A method for producing an optically active or racemic aminal derivative.
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7036679A JPS55162787A (en) | 1979-06-04 | 1979-06-04 | Aminal derivative and its preparation |
| US06/089,356 US4337346A (en) | 1978-11-02 | 1979-10-30 | α-Hydroxyaldehyde and a process for preparing the same |
| DE8181108507T DE2966001D1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic diazabicyclooctane derivatives |
| EP81108507A EP0048501B1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic diazabicyclooctane derivatives |
| DE7979302419T DE2965322D1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic aminal derivatives, process for preparing same and for converting same to alpha-hydroxyaldehydes |
| DE8181108506T DE2967419D1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic alpha-hydroxyaldehydes and benzyl derivatives thereof |
| EP81108506A EP0050351B1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic alpha-hydroxyaldehydes and benzyl derivatives thereof |
| EP79302419A EP0011417B1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic aminal derivatives, process for preparing same and for converting same to alpha-hydroxyaldehydes |
| US06/257,587 US4383122A (en) | 1978-11-02 | 1981-04-27 | Process for preparing α-hydroxyaldehyde |
| US06/457,666 US4584387A (en) | 1978-11-02 | 1983-01-13 | Acyl and ester derivatives of 1,3-diazabicyclo[3,3,0]octane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7036679A JPS55162787A (en) | 1979-06-04 | 1979-06-04 | Aminal derivative and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55162787A JPS55162787A (en) | 1980-12-18 |
| JPS6364435B2 true JPS6364435B2 (en) | 1988-12-12 |
Family
ID=13429360
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7036679A Granted JPS55162787A (en) | 1978-11-02 | 1979-06-04 | Aminal derivative and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS55162787A (en) |
-
1979
- 1979-06-04 JP JP7036679A patent/JPS55162787A/en active Granted
Non-Patent Citations (1)
| Title |
|---|
| CHEMISTRY LETTERS * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55162787A (en) | 1980-12-18 |
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