JPS6033829B2 - Production method of substituted pyridine - Google Patents
Production method of substituted pyridineInfo
- Publication number
- JPS6033829B2 JPS6033829B2 JP11692375A JP11692375A JPS6033829B2 JP S6033829 B2 JPS6033829 B2 JP S6033829B2 JP 11692375 A JP11692375 A JP 11692375A JP 11692375 A JP11692375 A JP 11692375A JP S6033829 B2 JPS6033829 B2 JP S6033829B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- substituted pyridine
- alkyl group
- general formula
- carbon atoms
- 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title claims description 7
- 150000003222 pyridines Chemical class 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 150000004705 aldimines Chemical class 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 150000002825 nitriles Chemical class 0.000 claims description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 8
- -1 aldimine compound Chemical class 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- KJNZQKYSNAQLEO-UHFFFAOYSA-N 2-(4-methylphenyl)pyridine Chemical compound C1=CC(C)=CC=C1C1=CC=CC=N1 KJNZQKYSNAQLEO-UHFFFAOYSA-N 0.000 description 1
- WWMRJCUZPJJWBC-UHFFFAOYSA-N 4-methyl-2-phenylpyridine Chemical compound CC1=CC=NC(C=2C=CC=CC=2)=C1 WWMRJCUZPJJWBC-UHFFFAOYSA-N 0.000 description 1
- VCZNNAKNUVJVGX-UHFFFAOYSA-N 4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C=C1 VCZNNAKNUVJVGX-UHFFFAOYSA-N 0.000 description 1
- 240000008564 Boehmeria nivea Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 description 1
- 244000241257 Cucumis melo Species 0.000 description 1
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940043350 citral Drugs 0.000 description 1
- PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- ORPGAOYOWYKKCL-UHFFFAOYSA-N n-tert-butylbut-2-en-1-imine Chemical compound CC=CC=NC(C)(C)C ORPGAOYOWYKKCL-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical group CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Description
【発明の詳細な説明】
従来、ピリジン環の合成は種々の方法が提案され一部実
用化されているが、本発明はアルドィミン化合物とニト
リル化合物とから容易にかつ高収率で置換ピリジンを製
造する方法である。[Detailed Description of the Invention] Conventionally, various methods have been proposed for the synthesis of pyridine rings, and some of them have been put into practical use, but the present invention enables the production of substituted pyridine easily and in high yield from an aldimine compound and a nitrile compound. This is the way to do it.
本発明はＱ，８‐リ不飽和アルドィミンとニトリルとを
リチウムアルキルアミドの存在下反応させることによっ
て置換ピリジンを得る方法であり、その反応過程を示す
と次のようになる。The present invention is a method for obtaining a substituted pyridine by reacting a Q,8-ly unsaturated aldimine and a nitrile in the presence of a lithium alkylamide, and the reaction process is as follows.
この反応操作は先ず実施例に示す−７尊０のような低温
でリチウムアミドとアルドイミンとを混合してカルバニ
オンを生成させ、次にニトリルを加え混合し、徐々に室
温附近の温度とした後反応させればよい。This reaction operation is performed by first mixing lithium amide and an aldimine at a low temperature such as -7-0 as shown in the example to form a carbanion, then adding and mixing nitrile, gradually bringing the temperature to around room temperature, and then reacting. Just let it happen.
反応終了後は氷水等で温度の上昇を防ぎながら処理した
後、蒸留その他の適切な手段で目的物を置換ピリジンを
取得すればよい。本発明に使用されるＱ，Ｐ−不飽和ア
ルドイミンは一般式【１）で示される化合物であり、（
式中ＲＩは水素又は炭素数１〜２０のアルキル基、アル
ケニル基を示す。）また使用されるニトリルとしては一
般式■でで示される化合物である。After the reaction is completed, the reaction mixture may be treated with ice water or the like while preventing a rise in temperature, and then the target product, substituted pyridine, may be obtained by distillation or other appropriate means. The Q,P-unsaturated aldoimine used in the present invention is a compound represented by the general formula [1], and (
In the formula, RI represents hydrogen, an alkyl group having 1 to 20 carbon atoms, or an alkenyl group. ) Also, the nitrile used is a compound represented by the general formula (2).
Ｒ３一ＣＮ 【２１（
式中Ｒ３は炭素数１〜８のアルキル基を示す。R3-CN [21(
In the formula, R3 represents an alkyl group having 1 to 8 carbon atoms.
ただしＲ，が水素又はメチル基の場合には、ピリジン環
を与えないＲ３である炭素数１〜３のアルキル基は除か
れる。）反応触媒であるリチウムアルキルアミドは、そ
のアルキル基が例えばブチル、プロピル、エチル等の低
級アルキル基であるものが使用され、また反応はエーテ
ル、低級炭化水素等の低い融点の溶媒が使用される。ア
ルドイミンとニトリルとの反応モル比は、１：１であれ
ばよく或いはいづれか一方を過剰に使用してもよい。However, when R is hydrogen or a methyl group, the alkyl group having 1 to 3 carbon atoms that does not form a pyridine ring is excluded. ) The lithium alkylamide used as the reaction catalyst is one whose alkyl group is a lower alkyl group such as butyl, propyl, ethyl, etc., and a low melting point solvent such as ether or lower hydrocarbon is used for the reaction. . The reaction molar ratio of aldimine and nitrile may be 1:1, or either one may be used in excess.
またリチウムアルキルアミドはアルドィミン又はニトリ
ルに対して当モル以下の使用が好ましい。このように反
応して得られる置換ピリジンは一般式糊で示される化合
物であり、合成香料や、医薬、農薬等の原料としての用
途が期待される。Further, it is preferable to use the lithium alkylamide in an amount equal to or less than the equivalent molar amount to the aldimine or nitrile. The substituted pyridine obtained by this reaction is a compound represented by the general formula, and is expected to be used as a raw material for synthetic fragrances, medicines, agricultural chemicals, etc.
（式中Ｒ１，Ｒ３は前式‘１１，（２｝と同じ。）実施
例 １シトラールアルドイミン（すなわちＮ−ｔーフチ
ル〔３，７−ジメチルー２，６ーオクタジエニリデン〕
ーアミン）とりチウムジイソブロピルアミドとをモル比
１：１で無水エーテル中−７８こ０で混合し、１時間反
応した（カルバニオンの生成）。(In the formula, R1 and R3 are the same as the previous formula '11, (2}.) Example 1 Citral aldimine (i.e. N-t-phthyl [3,7-dimethyl-2,6-octadienylidene])
-amine) and tium diisopropylamide were mixed at a molar ratio of 1:1 in anhydrous ether at -78% and reacted for 1 hour (formation of carbanion).
そのままの温度でこのカルバニオンに当モル比の蒸留し
たばかりのィソブチニトリルを滴下した後、室温にまで
ゆっくり昇温し、２独特間縄梓反応した。反応生成物を
砕氷上に注ぎ、有機層を数回水で洗総した後、乾燥（無
水苧硝）し、蒸留分取により２−ィソプロピル−４−〔
４ーメチル−３ーベンテニル〕ーピリジンを仕込アルド
イミンに対して６３％の収率で得た。これのＮＭＲ（核
磁気共鳴）、ＩＲ（赤外線吸収スペクトル）、ＭＡＳＳ
（質量分析）の結果を示す。〔ＭＡＳＳ（ｍ／夕）：Ｍ
十２０３；ＩＲ（ｎｅａｔ、抑１ ）：１６０３，８２
５；ＮＭ凪（Ｃ ＣＩ４，Ｓ〕８．２７（ＩＨ，ｄ，Ｊ
＝５．班Ｚ），６．８２（ＩＨ，Ｓ），６．７９（ＩＨ
，ｄ，Ｊ＝５．班２〕，５．０６（ＩＨ，ｔ，Ｊ：７，
皿２），２，９３（ＩＨ．ｍ．Ｊ＝６，斑２），２．６
２〜２．１６（瓜，ｍ），１．６３（幻，Ｓ），１．５
０（班，Ｓ），１．２５（細．ｄ，Ｊ；６．弧２〕。実
施例 ２
実施例１で使用のィソブチロニトリルをプロピオニトリ
ルに代えた以外は、実施例１と同様に操作し、２−エチ
ル−４一〔４ーメチルー３ーベンテニル）ーピリジンを
収率４６％で得た。An equimolar ratio of freshly distilled isobutynitrile was added dropwise to the carbanion at the same temperature, and then the temperature was slowly raised to room temperature to cause a two-part reaction. The reaction product was poured onto crushed ice, the organic layer was washed several times with water, dried (anhydrous ramie), and fractionated by distillation to obtain 2-isopropyl-4-[
4-Methyl-3-bentenyl]-pyridine was obtained in a yield of 63% based on the charged aldimine. This NMR (nuclear magnetic resonance), IR (infrared absorption spectrum), MASS
(Mass spectrometry) results are shown. [MASS (m/evening): M
1203; IR (neat, suppression 1): 1603,82
5; NM Nagi (C CI4, S) 8.27 (IH, d, J
=5. Group Z), 6.82 (IH, S), 6.79 (IH
, d, J=5. Group 2], 5.06 (IH, t, J: 7,
Dish 2), 2,93 (IH.m.J=6, Spot 2), 2.6
2-2.16 (melon, m), 1.63 (phantom, S), 1.5
0 (Square, S), 1.25 (Fine. d, J; 6. Arc 2). Example 2 Same as Example 1 except that isobutyronitrile used in Example 1 was replaced with propionitrile. In the same manner, 2-ethyl-4-[4-methyl-3-bentenyl)-pyridine was obtained in a yield of 46%.
実施例 ３
８ーメチルクロトンアルドイミン（すなわちＮ一ｔーブ
チル〔３ーメチルー２ーブテニリデン〕アミン）とペン
ゾニトリルとをモル比１：１リチウムジィソプロピルア
ミドの存在下で、実施例１の手順に準じて反応した結果
、２−フェニルー４−メチルピリジンをアルドイミン仕
込基準３８％の収率で得た。Example 3 8-Methylcrotonaldimine (i.e. N-tert-butyl[3-methyl-2-butenylidene]amine) and penzonitrile in a 1:1 molar ratio in the presence of lithium diisopropylamide according to the procedure of Example 1. As a result of the reaction, 2-phenyl-4-methylpyridine was obtained in a yield of 38% based on the aldimine charge.
実施例 ４，５
クロトンアルドイミン（すなわちＮ−ｔーブチル−〔２
ーブテニリデン〕アミン）を１：１のモル比でペンゾニ
トリル又はＰートルイックニトリルと実施例３と同様に
反応させた結果、夫々２−フェニルーピリジン（収率２
２％）、２−（Ｐ−トリル）ピリジン（収率２４％）を
得た。Examples 4,5 Crotonaldimine (i.e. N-t-butyl-[2
-butenylidene]amine) with benzonitrile or P-toluic nitrile at a molar ratio of 1:1 in the same manner as in Example 3.
2%), 2-(P-tolyl)pyridine (yield 24%) was obtained.
尚実施例１〜４の結果を表１に示す。表１
註・（づ 仕込ァルドィミン 、 ｂ アル ミ
ン・得られたピリジンはＮＭＲ．ＩＲ．ＭＡＳＳ等でそ
の構造を確認した。The results of Examples 1 to 4 are shown in Table 1. Table 1 Note: The structure of the obtained pyridine was confirmed by NMR, IR, MASS, etc.
Claims (1)
ンと一般式（２）で示されるニトリルとをリチウムジア
ルキルアミドの存在下に反応させることを特徴とする一
般式（３）で示される置換ピリジンの製法。 ▲数式、化学式、表等があります▼ 式（１）〜（３）中Ｒ＾１は水素又は炭素数１〜１０
のアルキル基、アルケニル基を、Ｒ＾２は炭素数１〜８
のアルキル基を Ｒ＾３は炭素数１〜４の低級アルキル基、アルケニル基
、アリル基及びアラルキル基をを示す。 ただしＲ＾１が水素又はメチル基の場合にはＲ＾３は炭
素数１〜３のアルキル基は除外される。[Claims] 1. A general formula characterized by reacting an α,β-unsaturated aldimine represented by general formula (1) with a nitrile represented by general formula (2) in the presence of lithium dialkylamide. A method for producing substituted pyridine shown in (3). ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In formulas (1) to (3), R^1 is hydrogen or carbon number 1 to 10
an alkyl group, alkenyl group, R^2 has 1 to 8 carbon atoms
R^3 represents a lower alkyl group having 1 to 4 carbon atoms, an alkenyl group, an allyl group, and an aralkyl group. However, when R^1 is hydrogen or a methyl group, R^3 is an alkyl group having 1 to 3 carbon atoms.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11692375A JPS6033829B2 (en) | 1975-09-27 | 1975-09-27 | Production method of substituted pyridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11692375A JPS6033829B2 (en) | 1975-09-27 | 1975-09-27 | Production method of substituted pyridine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5242882A JPS5242882A (en) | 1977-04-04 |
| JPS6033829B2 true JPS6033829B2 (en) | 1985-08-05 |
Family
ID=14699009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11692375A Expired JPS6033829B2 (en) | 1975-09-27 | 1975-09-27 | Production method of substituted pyridine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6033829B2 (en) |
-
1975
- 1975-09-27 JP JP11692375A patent/JPS6033829B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5242882A (en) | 1977-04-04 |
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