JPH01139566A - Production of pyridine-2,3-dicarboxylic derivative - Google Patents
Production of pyridine-2,3-dicarboxylic derivativeInfo
- Publication number
- JPH01139566A JPH01139566A JP29580587A JP29580587A JPH01139566A JP H01139566 A JPH01139566 A JP H01139566A JP 29580587 A JP29580587 A JP 29580587A JP 29580587 A JP29580587 A JP 29580587A JP H01139566 A JPH01139566 A JP H01139566A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- pyridine
- dicarboxylic acid
- formulas
- alkyl group
- 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.)
- Granted
Links
- GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical class OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 150000003863 ammonium salts Chemical class 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 10
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 6
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 5
- 150000002576 ketones Chemical class 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 abstract description 8
- -1 enamine derivative of oxaloacetic acid ester Chemical class 0.000 abstract description 7
- 150000003839 salts Chemical class 0.000 abstract description 6
- 238000009835 boiling Methods 0.000 abstract description 3
- 230000002363 herbicidal effect Effects 0.000 abstract description 3
- 239000004009 herbicide Substances 0.000 abstract description 3
- 150000002081 enamines Chemical class 0.000 abstract description 2
- CGMJIXLCLAOYLR-UHFFFAOYSA-N 2-(4,5-dihydro-1h-imidazol-2-yl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1C1=NCCN1 CGMJIXLCLAOYLR-UHFFFAOYSA-N 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- JLIDVCMBCGBIEY-UHFFFAOYSA-N vinyl ethyl ketone Natural products CCC(=O)C=C JLIDVCMBCGBIEY-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 5
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- GEHMBYLTCISYNY-UHFFFAOYSA-N Ammonium sulfamate Chemical compound [NH4+].NS([O-])(=O)=O GEHMBYLTCISYNY-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- FFZBMYDDXULOPW-AATRIKPKSA-N diethyl (e)-2-aminobut-2-enedioate Chemical compound CCOC(=O)\C=C(\N)C(=O)OCC FFZBMYDDXULOPW-AATRIKPKSA-N 0.000 description 3
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- GMLDCZYTIPCVMO-UHFFFAOYSA-N 2-methylidenebutanal Chemical compound CCC(=C)C=O GMLDCZYTIPCVMO-UHFFFAOYSA-N 0.000 description 1
- ISSPPDIMZKGLKN-UHFFFAOYSA-N 2-propan-2-yloxycarbonylpyridine-3-carboxylic acid Chemical compound CC(C)OC(=O)C1=NC=CC=C1C(O)=O ISSPPDIMZKGLKN-UHFFFAOYSA-N 0.000 description 1
- PFRKUTUSSSDRQV-UHFFFAOYSA-N C(C1=CC=CC=C1)OC(=O)C=1C(=NC=CC=1)C(=O)OCC1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)OC(=O)C=1C(=NC=CC=1)C(=O)OCC1=CC=CC=C1 PFRKUTUSSSDRQV-UHFFFAOYSA-N 0.000 description 1
- FKQCVQSCXKCFDA-UHFFFAOYSA-N CC1=NC(=C(C=C1)C(=O)OCC2=CC=CC=C2)C(=O)OCC3=CC=CC=C3 Chemical compound CC1=NC(=C(C=C1)C(=O)OCC2=CC=CC=C2)C(=O)OCC3=CC=CC=C3 FKQCVQSCXKCFDA-UHFFFAOYSA-N 0.000 description 1
- CVNRSOVDWWTQFZ-UHFFFAOYSA-N CCC1=CC(=C(N=C1)C(=O)OCC2=CC=CC=C2)C(=O)OCC3=CC=CC=C3 Chemical compound CCC1=CC(=C(N=C1)C(=O)OCC2=CC=CC=C2)C(=O)OCC3=CC=CC=C3 CVNRSOVDWWTQFZ-UHFFFAOYSA-N 0.000 description 1
- AZVKJEWUHZMZTM-UHFFFAOYSA-N CCOC(=O)C1=C(N=C(C=C1)C)C(=O)OC Chemical compound CCOC(=O)C1=C(N=C(C=C1)C)C(=O)OC AZVKJEWUHZMZTM-UHFFFAOYSA-N 0.000 description 1
- 238000000023 Kugelrohr distillation Methods 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- VSPXTWXXNZJEHM-UHFFFAOYSA-N diethyl 5-ethylpyridine-2,3-dicarboxylate Chemical compound CCOC(=O)C1=CC(CC)=CN=C1C(=O)OCC VSPXTWXXNZJEHM-UHFFFAOYSA-N 0.000 description 1
- XCKZEKXOGHWDMQ-UHFFFAOYSA-N diethyl 6-methylpyridine-2,3-dicarboxylate Chemical compound CCOC(=O)C1=CC=C(C)N=C1C(=O)OCC XCKZEKXOGHWDMQ-UHFFFAOYSA-N 0.000 description 1
- LIVYVINPLCASPD-UHFFFAOYSA-N diethyl pyridine-2,3-dicarboxylate Chemical compound CCOC(=O)C1=CC=CN=C1C(=O)OCC LIVYVINPLCASPD-UHFFFAOYSA-N 0.000 description 1
- OIYDMGCIAJUICI-ONEGZZNKSA-N dimethyl (e)-2-aminobut-2-enedioate Chemical compound COC(=O)\C=C(\N)C(=O)OC OIYDMGCIAJUICI-ONEGZZNKSA-N 0.000 description 1
- CZGBLCUFEBWLRT-UHFFFAOYSA-N dimethyl 5-ethylpyridine-2,3-dicarboxylate Chemical compound CCC1=CN=C(C(=O)OC)C(C(=O)OC)=C1 CZGBLCUFEBWLRT-UHFFFAOYSA-N 0.000 description 1
- SQGLFNFFHCBMIC-UHFFFAOYSA-N dimethyl 6-methylpyridine-2,3-dicarboxylate Chemical compound COC(=O)C1=CC=C(C)N=C1C(=O)OC SQGLFNFFHCBMIC-UHFFFAOYSA-N 0.000 description 1
- YLGIBCYHQZTFQL-UHFFFAOYSA-N dimethyl pyridine-2,3-dicarboxylate Chemical compound COC(=O)C1=CC=CN=C1C(=O)OC YLGIBCYHQZTFQL-UHFFFAOYSA-N 0.000 description 1
- ZKGKILXDZKQKCY-ISLYRVAYSA-N dioctyl (E)-2-aminobut-2-enedioate Chemical compound N/C(/C(=O)OCCCCCCCC)=C/C(=O)OCCCCCCCC ZKGKILXDZKQKCY-ISLYRVAYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、ピリジン−２，３−ジカルボン酸エステル類
の製法に関する。本発明の方法で得られるピリジン−２
，３−ジカルボン酸エステル類は、除草剤２−（２−イ
ミダシリン−２−イル）ニコチン酸、エステル及び塩の
中間体として有用な物質である。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a method for producing pyridine-2,3-dicarboxylic acid esters. Pyridine-2 obtained by the method of the present invention
, 3-dicarboxylic acid esters are useful substances as intermediates for the herbicide 2-(2-imidacillin-2-yl)nicotinic acid, esters and salts.
（従来技術及び問題点）
ピリジン−２，３−ジカルボン酸類の製法としては、例
えば、オキザロ酢酸エステル［式（ＩＶ）でＸ＝Ｈ］を
式（Ｉｖ）
（式中、Ｒ１、Ｒ２はアルキル基、Ｘはハロゲン原子を
示す。）で表されるα−ハローオキザロ酢酸エステルに
変換した後、最低２モル当量のアンモニウム塩の存在下
、式（ＩＩ）
（式中、Ｒ３はアルキル基、Ｒ４は水素またはアルキル
基、Ｒ５はアルキル基を示す。）で表されるα、Ｉ３−
不飽和アルデヒドまたはケトンと反応させる方法が提唱
されている（特開昭６２−１０６０８１）。しかしなが
らこの方法では、オキザロ酢酸エステルを式（ＩＶ）で
表されるα−ハロ一体に変換する工程が必要であり、又
、この収率も低いといった問題があった。更に、α−ハ
ロ一体からピリジン−２，３−ジカルボン酸エステル類
を得るのに最低２モル当量のアンモニウム塩が必要であ
った。以上のように、これまでピリジン−２，３ｏジカ
ルボン酸類を、容易に人手できる出発原料から簡単な態
様で製造することを可能にするような方法はまだ提案さ
れていない。(Prior art and problems) As a method for producing pyridine-2,3-dicarboxylic acids, for example, oxaloacetate [X=H in formula (IV)] is converted to the formula (Iv) (wherein R1 and R2 are alkyl groups). , X represents a halogen atom), and then in the presence of at least 2 molar equivalents of ammonium salt, the formula (II) (wherein R3 is an alkyl group and R4 is α, I3- represented by hydrogen or an alkyl group, R5 represents an alkyl group.
A method of reacting with an unsaturated aldehyde or ketone has been proposed (Japanese Patent Application Laid-Open No. 106081/1981). However, this method requires a step of converting oxaloacetate into α-halo monomer represented by formula (IV), and the yield thereof is also low. Furthermore, at least 2 molar equivalents of ammonium salt were required to obtain pyridine-2,3-dicarboxylic acid esters from α-halo monomers. As described above, no method has yet been proposed that enables the production of pyridine-2,3o dicarboxylic acids in a simple manner from starting materials that can be easily obtained manually.
（発明の目的）
従って、本発明の目的は、オキザロ酢酸エステルから容
易に得られる誘導体から一工程で、且つ、多量のアンモ
ニウム塩或いはアンモニアを必要としないピリジン−２
，３−ジカルボン酸エステル類を製造する方法を提供す
ることにある。この様な目的は下記の本発明によって達
成される。(Object of the Invention) Therefore, the object of the present invention is to produce pyridine-2 in one step from a derivative easily obtained from oxaloacetate and without the need for a large amount of ammonium salt or ammonia.
, 3-dicarboxylic acid esters. These objects are achieved by the invention described below.
（発明の構成）
即ち、本発明は、式（Ｉ）
（式中、Ｒ１、Ｒ２はアルキル基を示す。）で表される
オキザロ酢酸エステルのエナミン誘導体をアンモニウム
塩或いはアンモニアの存在下または非存在下、式（ＩＩ
）
（式中、Ｒ３からＲ５は水素またはアルキル基を示す。(Structure of the Invention) That is, the present invention provides an enamine derivative of oxaloacetate represented by formula (I) (wherein R1 and R2 represent an alkyl group) in the presence or absence of an ammonium salt or ammonia. Below, formula (II
) (In the formula, R3 to R5 represent hydrogen or an alkyl group.
）で表されるα、ｐ−不飽和アルデヒドまたはケトンと
反応させることを特徴とする式（ＩＩＩ）（式中Ｒ１、
Ｒ２、Ｒ３、Ｒ４及びＲ５は、式（Ｉ）及び（ＩＩ）で
規定したものと同様である）で表されるピリジン−２，
３−ジカルボン酸エステル類の製法に関するものである
。) (wherein R1,
R2, R3, R4 and R5 are the same as defined in formulas (I) and (II)) pyridine-2,
This invention relates to a method for producing 3-dicarboxylic acid esters.
以下本発明の具体的構成について詳細に説明する。The specific configuration of the present invention will be explained in detail below.
式（Ｉ）
（式中、Ｒ１、Ｒ２はアルキル基を示す。）で表される
オキザロ酢酸エステルのエナミン誘導体は、例えば、オ
キザロ酢酸エステルを有機溶媒中アンモニウム塩と加熱
することによって得られる（Ｃｈｅｍ。The enamine derivative of oxaloacetate represented by formula (I) (wherein R1 and R2 represent an alkyl group) can be obtained, for example, by heating oxaloacetate with an ammonium salt in an organic solvent (Chem. .
Ｂｅｒ、、９８．２９２０（１９６５）。Ｒ１、Ｒ２は
炭素数１から５のアルキル基又は、炭素数７がら９のア
ルキル基であり、入手の容易な点ではメチル又はエチル
基が、水添で対応する酸に変換できる点ではベンジル基
が好ましい。例えば、アミノマレイン酸ジメチルエステ
ル、アミノマレイン酸ジエチルエステル、アミノマレイ
ン酸メチルエチルエステル、アミノマレイン酸ジオクチ
ルエステル、アミノマレイン酸ジベンジルエステル等が
挙げられる。Ber, 98.2920 (1965). R1 and R2 are an alkyl group having 1 to 5 carbon atoms or an alkyl group having 7 to 9 carbon atoms, and methyl or ethyl groups are easily available, while benzyl groups are preferable because they can be converted into the corresponding acids by hydrogenation. is preferred. Examples include aminomaleic acid dimethyl ester, aminomaleic acid diethyl ester, aminomaleic acid methylethyl ester, aminomaleic acid dioctyl ester, aminomaleic acid dibenzyl ester, and the like.
式（ＩＩ）
で表されるα、１３−不飽和アルデヒドまたはケトンに
おいて、Ｒ３は、メチル基、エチル基等の炭素数１から
５のアルキル基または水素を意味する。へ及びＲ５は水
素原子又はメチル基、エチル基、ｎ−プロピル基等の炭
素数１から５のアルキル基を意味し、好ましくは水素原
子である。例えば、アクロレイン、エチルアクロレイン
、メチルビニルケトン等を挙げることができる。エチル
アクロレイン（式（ＩＩ）においてＲ３はエチル基、狗
は水素、Ｒ５は水素であるα、ｐ−不飽和アルデヒド）
はｎ−ブチルアルデヒドとホルマリンから特開昭５５−
８７７３５の方法により容易に製造できる。In the α,13-unsaturated aldehyde or ketone represented by formula (II), R3 means an alkyl group having 1 to 5 carbon atoms such as a methyl group or an ethyl group, or hydrogen. and R5 mean a hydrogen atom or an alkyl group having 1 to 5 carbon atoms such as a methyl group, an ethyl group, or an n-propyl group, preferably a hydrogen atom. Examples include acrolein, ethyl acrolein, methyl vinyl ketone, and the like. Ethyl acrolein (α,p-unsaturated aldehyde in which R3 is an ethyl group, dog is hydrogen, and R5 is hydrogen in formula (II))
is obtained from n-butyraldehyde and formalin in JP-A-55-
It can be easily manufactured by the method of No. 87735.
上記式（Ｉ）及び式（ＩＩ）の化合物を溶媒中、アンモ
ニウム塩或いはアンモニアの非存在下または存在下に、
室温又は溶媒の沸点までの温度範囲で反応［反応式（Ａ
）Ｉｇせることにより式（ＩＩＩ）（ＩＩＩ）
（式中Ｒ１、Ｒ２、Ｒ３及び−は、一般式（Ｉ）及び（
ＩＩ）で規定したものと同様である）で表されるピリジ
ン−２，３−ジカルボン酸エステル類を製造することが
できる。本発明の方法では、中間体であるジヒドロピリ
ジン（Ｖ）が反応系中で容易に脱水素されピリジン−２
，３−ジカルボン酸エステル類（ＩＩＩ）（例えば、ピ
リジン−２，３−ジカルボン酸ジメチルエステル、ピリ
ジン−２，３−ジカルボン酸ジエチルエステル、ピリジ
ン−２，３−ジカルボン酸メチルエチルエステル、ピリ
ジン−２，３−ジカルボン酸ジベンジルエステル、５−
エチルピリジン−２，３−ジカルボン酸ジメチルエステ
ル、５−エチルピリジン−２，３−ジカルボン酸ジエチ
ルエステル、５−エチルピリジン−２，３−ジカルボン
酸メチルエチルエステル、５−エチルピリジン−２，３
−ジカルボン酸ジベンジルエステル、６−メチルピリジ
ン−２，３−ジカルボン酸ジメチルエステル、６−メチ
ルピリジン−２，３−ジカルボン酸ジエチルエステル、
６−メチルピリジン−２，３−ジカルボン酸メチルエチ
ルエステル、６−メチルピリジン−２，３−ジカルボン
酸ジベンジルエステル等）が生成するのが特徴である。The compounds of formula (I) and formula (II) above in a solvent, in the absence or presence of an ammonium salt or ammonia,
Reaction at room temperature or in the temperature range up to the boiling point of the solvent [reaction formula (A
) Ig, formula (III) (III) (wherein R1, R2, R3 and - are the general formula (I) and (
Pyridine-2,3-dicarboxylic acid esters represented by (same as those defined in II)) can be produced. In the method of the present invention, the intermediate dihydropyridine (V) is easily dehydrogenated in the reaction system and pyridine-2
, 3-dicarboxylic acid esters (III) (e.g., pyridine-2,3-dicarboxylic acid dimethyl ester, pyridine-2,3-dicarboxylic acid diethyl ester, pyridine-2,3-dicarboxylic acid methylethyl ester, pyridine-2 , 3-dicarboxylic acid dibenzyl ester, 5-
Ethylpyridine-2,3-dicarboxylic acid dimethyl ester, 5-ethylpyridine-2,3-dicarboxylic acid diethyl ester, 5-ethylpyridine-2,3-dicarboxylic acid methylethyl ester, 5-ethylpyridine-2,3
-dicarboxylic acid dibenzyl ester, 6-methylpyridine-2,3-dicarboxylic acid dimethyl ester, 6-methylpyridine-2,3-dicarboxylic acid diethyl ester,
6-methylpyridine-2,3-dicarboxylic acid methyl ethyl ester, 6-methylpyridine-2,3-dicarboxylic acid dibenzyl ester, etc.) are produced.
本発明の方法に用いる溶媒としては、水又はアルコール
、炭化水素、芳香族炭化水素、ハロゲン化炭化水素、エ
ーテル、有機酸、エステル、及びアセトニトリルなどの
非プロトン性有機溶媒であるが、後処理及び経済性から
水又はアルコールが好ましい。アンモニウム塩或いはア
ンモニアは添加しなくても良いが、化合物（ＩＩＩ）の
収率上、（Ｉ）に対して等モルから３倍モル使用するこ
とができる。Solvents used in the method of the present invention include water or alcohols, hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, ethers, organic acids, esters, and aprotic organic solvents such as acetonitrile. Water or alcohol is preferred from the economic point of view. Although it is not necessary to add ammonium salt or ammonia, in view of the yield of compound (III), it can be used in an equimolar to three times molar amount relative to (I).
アンモニウム塩としては、塩化アンモニウム等の無機塩
またはスルファミン酸アンモニウム等の有機塩を挙げる
ことができるが、水溶媒の場合には塩化アンモニウム等
の無機塩が、アルコール溶媒の場合にはスルファミン酸
アンモニウム等の有機塩が好ましい。化合物（Ｉ）及び
（ＩＩ）のモル比については、（Ｉ）に対して（ＩＩ）
を１．０から２．５倍モル用いるのが、（Ｉ）に対する
収率及び（ＩＩ）の経済性の点で好ましい。又、反応液
の濃度としては、化合物（Ｉ）が５から４０％の範囲で
、反応温度については、５０°Ｃから溶媒の沸点の範囲
で行うのが反応速度の点で好ましい。Examples of ammonium salts include inorganic salts such as ammonium chloride and organic salts such as ammonium sulfamate. In the case of an aqueous solvent, inorganic salts such as ammonium chloride are used, and in the case of an alcohol solvent, ammonium sulfamate, etc. Organic salts of are preferred. Regarding the molar ratio of compounds (I) and (II), (II) to (I)
It is preferable to use 1.0 to 2.5 times the mole of (I) in terms of yield and economy of (II). Further, from the viewpoint of reaction rate, it is preferable that the concentration of the reaction solution is in the range of 5 to 40% of compound (I), and the reaction temperature is in the range of 50° C. to the boiling point of the solvent.
（実施例） 本発明を若干の実施例によって、更に詳細に説明する。(Example) The present invention will be explained in more detail by means of some examples.
例１
２、エチルアクロレイン［式（ＩＩ）において、Ｒ３＝
Ｅｔ。Example 1 2. Ethyl acrolein [In formula (II), R3=
Et.
Ｒ４＝ Ｒ５＝Ｈ１２，１６ｇ（０，０２６ｍｏｌ）、
アミノマレイン酸ジエチル［式（Ｉ）において、Ｒ１、
Ｒ２＝Ｅｔｌ５．６２ｇ（０，０３０ｍｏｌ）及びスル
ファミン酸アンモニウム９．２４ｇ（０，０８１ｍｏｌ
）をエタノール２２ｍ１中、還流下６時間反応させた。R4=R5=H12, 16g (0,026mol),
diethyl aminomaleate [in formula (I), R1,
R2 = Etl 5.62 g (0,030 mol) and ammonium sulfamate 9.24 g (0,081 mol)
) was reacted in 22 ml of ethanol under reflux for 6 hours.
反応液を室温に冷却し、減圧下で溶媒を留去した後、水
を加えトルエンで抽出した。有機相は、無水硫酸マグネ
シウムで乾燥後、減圧下で溶媒を留去し粗生成物７．０
７ｇを得た。粗生成物のＧＣ分析は、表題の化合物３．
１４ｇ（収率４８．５％）の生成を示した。粗生成物を
シリカゲルカラムで精製後、クーゲルロール蒸留により
純品２．９１ｇを得た。The reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure, water was added, and the mixture was extracted with toluene. After drying the organic phase over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain a crude product of 7.0
7g was obtained. GC analysis of the crude product revealed the title compound 3.
It showed the production of 14 g (yield 48.5%). After the crude product was purified using a silica gel column, 2.91 g of pure product was obtained by Kugelrohr distillation.
ｂ、ｐ、 １８２−１８５°Ｃ／ １ ｍｍＨｇＧＣＭ
ａｓｓ （ＣＩ） ２５２ ［Ｍ＋Ｈ］ＮＭＲδ（ＣＤ
Ｃ１３） ８．５６［ｄ、 ＩＨＩ、 ８．２５［ｄ、
ＩＨＩ、 ４．４３［ｑ。b, p, 182-185°C/1 mmHgGCM
ass (CI) 252 [M+H]NMRδ(CD
C13) 8.56[d, IHI, 8.25[d,
IHI, 4.43 [q.
２Ｈ］、 ４．３７［ｑ、 ２Ｈ］、 ２．７５［ｑ、
２Ｈ］、 １．４０［ｔ、 ３Ｈ］。2H], 4.37[q, 2H], 2.75[q,
2H], 1.40[t, 3H].
１．３６［ｔ、 ３Ｈ］、 １．２８［ｔ、 ３Ｈ］Ｉ
Ｒ（Ｎｅａｔ） ３４５０．２９８０．１７５０．１
５６０．１４６０．１３７０゜１０２０、９２０．８７
０．８００ ｃｍ−Ｉ例２
エタノール２２ｍ１中、２−エチルアクロレイン１式（
ＩＩ）において、Ｒ３＝Ｅｔ、 Ｒ４＝Ｒ５＝Ｈ］２．
１６ｇ（０，０２６ｍｏｌ）及びアミノマレイン酸ジエ
チル［式（Ｉ）において、Ｒ１、Ｒ２＝Ｅｔｌ ５．６
２ｇ（０，０３０ｍｏｌ）を用いて、アンモニウム塩或
いはアンモニアを加えないで、実施例１と同様にして、
粗生成物’１．０７ｇを得た。粗生成物のＧＣ分析は、
表題の化合物１．２９ｇ（収率２０．０％）の生成を示
した。1.36[t, 3H], 1.28[t, 3H]I
R (Neat) 3450.2980.1750.1
560.1460.1370°1020, 920.87
0.800 cm-I Example 2 In 22 ml of ethanol, 1 formula of 2-ethyl acrolein (
In II), R3=Et, R4=R5=H]2.
16 g (0,026 mol) and diethyl aminomaleate [in formula (I), R1, R2=Etl 5.6
In the same manner as in Example 1, using 2 g (0,030 mol) and without adding ammonium salt or ammonia,
1.07 g of crude product was obtained. GC analysis of the crude product was
It showed the formation of 1.29 g (yield 20.0%) of the title compound.
（発明の効果）
以上の説明から明らかな様に本発明の方法により、従来
用いられていた様なα−ハローオキザロ酢酸エステルを
用いることなく、オキザロ酢酸エステルより容易に得ら
れるエナミン誘導体から、多量のアンモニウム塩或いは
アンモニアを用いずに、ピリジン−２，３−ジカルボン
酸エステル類を製造することが可能になった。(Effects of the Invention) As is clear from the above explanation, the method of the present invention enables large amounts of enamine derivatives that can be easily obtained from oxaloacetate without using α-halooxaloacetate as conventionally used. It has now become possible to produce pyridine-2,3-dicarboxylic acid esters without using ammonium salts or ammonia.
出願人ダイセル化学工業株式会社Applicant Daicel Chemical Industries, Ltd.
Claims (2)
れる化合物をアンモニウム塩或いはアンモニアの存在下
または非存在下、式（II） ▲数式、化学式、表等があります▼（II） （式中、Ｒ＿３からＲ＿５は水素またはアルキル基を示
す。）で表されるα，β−不飽和アルデヒドまたはケト
ンと反応させることを特徴とする式（III） ▲数式、化学式、表等があります▼（III） （式中Ｒ＿１、Ｒ＿２、Ｒ＿３、Ｒ＿４及びＲ＿５は、
式（ I ）及び（II）で規定したものと同様である）で
表されるピリジン−２，３−ジカルボン酸エステル類の
製法。(1) Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R_1 and R_2 represent an alkyl group.) A compound represented by the formula (I) is prepared in the presence or absence of an ammonium salt or ammonia. Below, formula (II) ▲Mathematical formulas, chemical formulas, tables, etc.▼(II) Reacts with α,β-unsaturated aldehyde or ketone represented by (In the formula, R_3 to R_5 represent hydrogen or an alkyl group.) Formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R_1, R_2, R_3, R_4 and R_5 are
A method for producing pyridine-2,3-dicarboxylic acid esters represented by the formulas (I) and (II).
ル基、Ｒ＿４及びＲ＿５が水素である特許請求の範囲第
１項記載の方法。(2) The method according to claim 1, wherein in general formulas (I) to (III), R_3 is an ethyl group, and R_4 and R_5 are hydrogen.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29580587A JPH082882B2 (en) | 1987-11-24 | 1987-11-24 | Process for producing pyridine-2,3-dicarboxylic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29580587A JPH082882B2 (en) | 1987-11-24 | 1987-11-24 | Process for producing pyridine-2,3-dicarboxylic acid derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01139566A true JPH01139566A (en) | 1989-06-01 |
| JPH082882B2 JPH082882B2 (en) | 1996-01-17 |
Family
ID=17825394
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29580587A Expired - Lifetime JPH082882B2 (en) | 1987-11-24 | 1987-11-24 | Process for producing pyridine-2,3-dicarboxylic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH082882B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02204481A (en) * | 1988-12-01 | 1990-08-14 | Wacker Chemie Gmbh | Preparation of pyridine-2, 3-dicarboxylic acid ester |
| US5322948A (en) * | 1989-08-31 | 1994-06-21 | Hoechst Celanese Corporation | Process for preparing pyridinecarboxylic acid derivatives |
| WO2021202134A1 (en) * | 2020-03-30 | 2021-10-07 | Verdesian Life Sciences U.S., Llc | Oxaloacetate and related compounds as herbicidal agents |
-
1987
- 1987-11-24 JP JP29580587A patent/JPH082882B2/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02204481A (en) * | 1988-12-01 | 1990-08-14 | Wacker Chemie Gmbh | Preparation of pyridine-2, 3-dicarboxylic acid ester |
| US5008392A (en) * | 1988-12-01 | 1991-04-16 | Wacker-Chemie Gmbh | Process for the preparation of pyridine-2,3-dicarboxylic acid esters |
| US5322948A (en) * | 1989-08-31 | 1994-06-21 | Hoechst Celanese Corporation | Process for preparing pyridinecarboxylic acid derivatives |
| WO2021202134A1 (en) * | 2020-03-30 | 2021-10-07 | Verdesian Life Sciences U.S., Llc | Oxaloacetate and related compounds as herbicidal agents |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH082882B2 (en) | 1996-01-17 |
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