JPH04149179A - Production of acetylthiophene derivative - Google Patents
Production of acetylthiophene derivativeInfo
- Publication number
- JPH04149179A JPH04149179A JP27446990A JP27446990A JPH04149179A JP H04149179 A JPH04149179 A JP H04149179A JP 27446990 A JP27446990 A JP 27446990A JP 27446990 A JP27446990 A JP 27446990A JP H04149179 A JPH04149179 A JP H04149179A
- Authority
- JP
- Japan
- Prior art keywords
- derivative
- acetylthiophene
- formula
- acid
- ester
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 15
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical class CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 title claims abstract description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 28
- -1 2,5-thiophenedicarboxylic acid diester Chemical class 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 239000002585 base Substances 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
- 239000012312 sodium hydride Substances 0.000 claims description 4
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 3
- 239000003638 chemical reducing agent Substances 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 4
- OQLIBYCXBFTLKX-UHFFFAOYSA-N 2-methylsulfinyl-1-thiophen-2-ylethanone Chemical class CS(=O)CC(=O)C1=CC=CS1 OQLIBYCXBFTLKX-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 150000003385 sodium Chemical class 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000000034 method Methods 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ATLWDAOOUUVIKP-UHFFFAOYSA-N 1-(5-acetylthiophen-2-yl)ethanone Chemical compound CC(=O)C1=CC=C(C(C)=O)S1 ATLWDAOOUUVIKP-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 4
- CYUGNCLRGFKPAE-UHFFFAOYSA-N dimethyl thiophene-2,5-dicarboxylate Chemical compound COC(=O)C1=CC=C(C(=O)OC)S1 CYUGNCLRGFKPAE-UHFFFAOYSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PGBFYLVIMDQYMS-UHFFFAOYSA-N Methyl thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=CS1 PGBFYLVIMDQYMS-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000000397 acetylating effect Effects 0.000 description 2
- 239000001361 adipic acid Substances 0.000 description 2
- 235000011037 adipic acid Nutrition 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- FOLYMTHZDUYMGS-UHFFFAOYSA-N diethyl thiophene-2,5-dicarboxylate Chemical compound CCOC(=O)C1=CC=C(C(=O)OCC)S1 FOLYMTHZDUYMGS-UHFFFAOYSA-N 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- YCGAZNXXGKTASZ-UHFFFAOYSA-N thiophene-2,5-dicarboxylic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)S1 YCGAZNXXGKTASZ-UHFFFAOYSA-N 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RINJOJVOROXXOL-UHFFFAOYSA-N 1-(2-acetylthiophen-3-yl)ethanone Chemical compound CC(=O)C=1C=CSC=1C(C)=O RINJOJVOROXXOL-UHFFFAOYSA-N 0.000 description 1
- DQCRHXGMBKPIEI-UHFFFAOYSA-N 2-(5-acetylthiophen-2-yl)acetic acid Chemical compound CC(=O)C1=CC=C(CC(O)=O)S1 DQCRHXGMBKPIEI-UHFFFAOYSA-N 0.000 description 1
- JCCCMAAJYSNBPR-UHFFFAOYSA-N 2-ethylthiophene Chemical compound CCC1=CC=CS1 JCCCMAAJYSNBPR-UHFFFAOYSA-N 0.000 description 1
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 1
- QQVIOEXFJFFVID-UHFFFAOYSA-N 3-acetylthiophene-2-carboxylic acid Chemical compound CC(=O)C=1C=CSC=1C(O)=O QQVIOEXFJFFVID-UHFFFAOYSA-N 0.000 description 1
- VSHPLUBHIUFLES-UHFFFAOYSA-N 5-acetylthiophene-2-carbonitrile Chemical compound CC(=O)C1=CC=C(C#N)S1 VSHPLUBHIUFLES-UHFFFAOYSA-N 0.000 description 1
- LIKIMWYKJUFVJP-UHFFFAOYSA-N 5-acetylthiophene-2-carboxylic acid Chemical compound CC(=O)C1=CC=C(C(O)=O)S1 LIKIMWYKJUFVJP-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000007033 dehydrochlorination reaction Methods 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- KWZUUCHRIBVBJW-UHFFFAOYSA-N dibutyl thiophene-2,5-dicarboxylate Chemical compound CCCCOC(=O)C1=CC=C(C(=O)OCCCC)S1 KWZUUCHRIBVBJW-UHFFFAOYSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- PBAPJOIMLUOPOP-UHFFFAOYSA-N dipropan-2-yl thiophene-2,5-dicarboxylate Chemical compound CC(C)OC(=O)C1=CC=C(C(=O)OC(C)C)S1 PBAPJOIMLUOPOP-UHFFFAOYSA-N 0.000 description 1
- TZTOBOROVOKWCM-UHFFFAOYSA-N dipropyl thiophene-2,5-dicarboxylate Chemical compound CCCOC(=O)C1=CC=C(C(=O)OCCC)S1 TZTOBOROVOKWCM-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PDIKYTHWLCYLEG-UHFFFAOYSA-N ethyl 5-acetylthiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(C(C)=O)S1 PDIKYTHWLCYLEG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052945 inorganic sulfide Chemical class 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
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 239000011707 mineral 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
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003799 water insoluble solvent Substances 0.000 description 1
Landscapes
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、アセチルチオフェン誘導体、即ち５−アセチ
ル−２−チオフェンカルボン酸エステル及び２，５−ジ
アセチルチオフェンの新規な製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a novel method for producing acetylthiophene derivatives, namely 5-acetyl-2-thiophenecarboxylic acid ester and 2,5-diacetylthiophene.
５−アセチル−２−チオフェンカルボン酸エステルから
導かれる５〜アセチル−２−チオフェンカルボン酸は、
例えば、特開昭５０−２５５６２号公報や特開昭５０−
７６０６９号公Ｍに記載されている不整脈、各種心疾患
及び高血圧治療剤であるチエニルチアゾリルチオアミノ
アルコール誘導体
Ｈ３
の重要な中間体である。5-acetyl-2-thiophenecarboxylic acid derived from 5-acetyl-2-thiophenecarboxylic acid ester is
For example, JP-A-50-25562 and JP-A-50-
It is an important intermediate of the thienylthiazolylthioamino alcohol derivative H3, which is a therapeutic agent for arrhythmia, various heart diseases, and hypertension, and is described in Publication No. 76069 M.
［従来の技術・発明が解決しようとする課題］従来、５
−アセチル−２−チオフェンカルボン酸エステル及び、
２，５−ジアセチルチオフェンを工業的に容易に且つ高
収率にて製造し得る方法は知られていない。例えば、５
−アセチル−２−チオフェンカルボン酸の製造方法とし
て、５−シアノ−２−アセチルチオフェンの加水分解に
よる方法（Ｊ、Ｃｈｅｍ、Ｓｏｃ、、 １９３７．９
４１） 、２． ５−ジアセチルチオフェンの酸化によ
る方法（Ｊ、 Ａｍ、 Ｃｈｅｍ。[Problems to be solved by conventional technology/invention] Conventionally, 5
-acetyl-2-thiophenecarboxylic acid ester and
There is no known method for producing 2,5-diacetylthiophene industrially easily and in high yield. For example, 5
- As a method for producing acetyl-2-thiophenecarboxylic acid, a method by hydrolysis of 5-cyano-2-acetylthiophene (J, Chem, Soc, 1937.9
41), 2. Method by oxidation of 5-diacetylthiophene (J, Am, Chem.
Ｓａｃ、、 ６９．１０１２ （１９４７））、２−テ
ノイル酸エステルのアシル化による方法（Ａｎｎ、 ｄ
ｅｒ Ｃｈｅｍ、、 １ （１９６２））、２−メチル
−２′−チエニル−１，３ジオキソランのカルボキシル
化反応による方法、２−チエニル酢酸のアセチル化によ
って得られる５−アセチル−２−チエニル酢酸又はその
エステルを酸化する方法（特開昭５３−１４１２６４号
公報）等が知られているか、いずれも工業的には原料、
反応の安全性や制御性からみて好ましい方法ではない。Sac, 69.1012 (1947)), the method by acylation of 2-thenoyl esters (Ann, d
er Chem, 1 (1962)), a method by carboxylation reaction of 2-methyl-2'-thienyl-1,3 dioxolane, 5-acetyl-2-thienyl acetic acid obtained by acetylation of 2-thienyl acetic acid, or its There are known methods for oxidizing esters (Japanese Unexamined Patent Publication No. 53-141264), and none of them are industrially suitable for raw materials,
This is not a preferable method from the viewpoint of reaction safety and controllability.
そこで、これらの方法における問題を解決するために、
特開昭６３−１０７９７４号公報や特開昭６２−２６５
２８２号公報に記載されているように、２−（α−アル
コキシイミノ）エチルチオフェンをアセチル化する方法
か提案されているか、この方法は反応工程数か多く、決
して工業的に有利な方法ではない。Therefore, in order to solve the problems with these methods,
JP-A-63-107974 and JP-A-62-265
As described in Publication No. 282, has a method been proposed for acetylating 2-(α-alkoxyimino)ethylthiophene? This method requires many reaction steps and is by no means an industrially advantageous method. .
また、前記２，５−ジアセチルチオフェンの製造方法と
しては、例えば、２−アセチルチオフェンをアセチル化
する方法（Ｊ、Ａｒｎ、Ｃｈｅｍ、Ｓｏｃ、、 ６９゜
１０１２ （１９４７））か知られているが、収率か極
めて低く工業的に有利な方法ではない。Further, as a method for producing the 2,5-diacetylthiophene, for example, a method of acetylating 2-acetylthiophene (J. Arn. Chem. Soc., 69°1012 (1947)) is known. The yield is extremely low and it is not an industrially advantageous method.
［課題を解決するだめの手段］
二のような状況に鑑みて本発明者らは、前記した５−ア
セチル−２−チオフェンカルボン酸エステル及び２．５
−ジアセチルチオフェンの工業的に有利な製造方法を見
出すべく鋭意研究し、出発原料として２．５−チオフェ
ンジカルボン酸ジエステル（二着目した。[Means for Solving the Problem] In view of the situation described in 2.
-We conducted extensive research to find an industrially advantageous production method for diacetylthiophene, and focused on 2,5-thiophenedicarboxylic acid diester as a starting material.
すなわち、２，５−チオフェンジカルボン酸ジエステル
とジメチルスルホキシドを反応させ、次いて還元するこ
とによりワンポットで効率よく目的とするアセチルチオ
フェン誘導体が得られることを見出し本発明に至った。That is, the inventors have discovered that the desired acetylthiophene derivative can be efficiently obtained in one pot by reacting 2,5-thiophenedicarboxylic acid diester with dimethyl sulfoxide and then reducing the mixture, leading to the present invention.
即ち、本発明の要旨は、
一般式（１）
〔式中、Ｒは炭素数１〜４のアルキル基を示す。〕で表
わされる２、５−チオフェンジカルボン酸ジエステルに
塩基の存在下てジメチルスルホキシドを反応させ、
一般式（ＩＩ）
〔式中、Ｙは−ＯＲまたは−ＣＨ２ＳＯＣＨ３、Ｒは炭
素数１〜４のアルキル基を示す。〕で表わされる（メチ
ルスルフィニル）アセチルチオフェン誘導体を得、次い
で還元することを特徴とする、一般式（Ｉｎ）
〔式中、Ｚは−ＯＲまたは−ＣＨ３、Ｒは炭素数１〜４
のアルキル基を示す。〕
て表わされるアセチルチオフェン誘導体の製造方法に関
する。That is, the gist of the present invention is as follows: General formula (1) [wherein R represents an alkyl group having 1 to 4 carbon atoms]. ] The 2,5-thiophenedicarboxylic acid diester represented by the formula (II) is reacted with dimethyl sulfoxide in the presence of a base to obtain the formula (II) [wherein, Y is -OR or -CH2SOCH3, and R is an alkyl group having 1 to 4 carbon atoms]. Indicates the group. [In the formula, Z is -OR or -CH3, and R is a carbon number of 1 to 4].
represents an alkyl group. ] This invention relates to a method for producing an acetylthiophene derivative represented by:
前記一般式（Ｉ）、（ＩＩ）及び（ＩＩ［）において、
Ｒは炭素数１〜４のアルキル基を示し、このアルキル基
は直鎖状でも分岐状でもよい。従って、かかるアルキル
基の具体例としては、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、
Ｓ−ブチル基及び１−ブチル基を挙げることかできる。In the general formulas (I), (II) and (II[),
R represents an alkyl group having 1 to 4 carbon atoms, and this alkyl group may be linear or branched. Therefore, specific examples of such alkyl groups include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group,
Mention may be made of the S-butyl group and the 1-butyl group.
本発明の前記一般式（Ｉ）で表される２、５−チオフェ
ンジカルボン酸ジエステルの具体例としては、２．５−
チオフェンジカルボン酸ジメチルエステル、２，５−チ
オフェンジカルボン酸ジエチルエステル、２，５−チオ
フェンジカルボン酸ジ−ｎ−プロピルエステル、２，５
−チオフェンジカルボン酸ジ−イソプロピルエステル、
２，５−チオフェンジカルボン酸ジ−ｎ−ブチルエステ
ル等を挙げることがてきる。Specific examples of the 2,5-thiophenedicarboxylic acid diester represented by the general formula (I) of the present invention include 2,5-
Thiophenedicarboxylic acid dimethyl ester, 2,5-thiophenedicarboxylic acid diethyl ester, 2,5-thiophenedicarboxylic acid di-n-propyl ester, 2,5
-thiophenedicarboxylic acid di-isopropyl ester,
Examples include 2,5-thiophenedicarboxylic acid di-n-butyl ester.
２．５−チオフェンジカルボン酸ジエステルは、例えば
特願平１−６１１８５号に記載されている製造方法又は
これに準じる方法により、アジピン酸から容易に合成す
ることかできる。即ち、アジピン酸から誘導されるα、
α′−ジハロアジピン酸ジエステルと無機硫化塩とを水
不溶性溶媒と水からなる２相系溶媒中で反応させて得ら
れるテトラヒドロチオフェンジカルボン酸ジエステルを
ハロゲン化し、引き続き脱ハロゲン化水素反応させるこ
とにより得られる。2,5-thiophenedicarboxylic acid diester can be easily synthesized from adipic acid, for example, by the production method described in Japanese Patent Application No. 1-61185 or a method analogous thereto. That is, α derived from adipic acid,
Obtained by halogenating a tetrahydrothiophene dicarboxylic acid diester obtained by reacting an α'-dihaloadipate diester and an inorganic sulfide salt in a two-phase solvent consisting of a water-insoluble solvent and water, followed by a dehydrohalogenation reaction. .
本発明において、中間体である一般式（ＩＩＩ）て表さ
れる（メチルスルフィニル）アセチルチオフェン誘導体
を単離し、その後還元することにより目的物を得ること
も可能であるか、該中間体は比較的不安定であるため単
離することなく直接アセチルチオフェン誘導体に導く方
法が好ましい。In the present invention, is it possible to obtain the target product by isolating the intermediate (methylsulfinyl)acetylthiophene derivative represented by the general formula (III) and then reducing it? Since it is unstable, a method that directly leads to an acetylthiophene derivative without isolation is preferred.
一般式（Ｉ）て表される２、５−チオフェンジカルボン
酸ジエステルとジメチルスルホキシドを反応させ一般式
（ＩＩ）で表される（メチルスルフィニル）アセチルチ
オフェン誘導体となす際に用いる塩基としては、水素化
ナトリウム、水素化カリウム等の水素化アルカリ金属、
ｔ−ブトキシカリウム、ｔ−ブトキシナトリウム等のｔ
−ブトキシアルカリ金属等を使用することができるが、
好ましくは水素化ナトリウムである。The base used when reacting the 2,5-thiophenedicarboxylic acid diester represented by the general formula (I) with dimethyl sulfoxide to form the (methylsulfinyl)acetylthiophene derivative represented by the general formula (II) is hydrogenated. Alkali metal hydrides such as sodium and potassium hydride,
t such as t-butoxypotassium, t-butoxysodium, etc.
- Butoxyalkali metals etc. can be used, but
Preferred is sodium hydride.
塩基およびジメチルスルホキシドの使用量は、目的によ
り異なる。すなわち２，５−チオフェンジカルボン酸ジ
エステルの片方のエステルを（メチルスルフィニル）ア
セチルに変換し、一般式〔式中、Ｒは炭素数１〜４のア
ルキル基を示す。〕で表される５−（メチルスルフィニ
ル）アセチル２−チオフェンカルボン酸エステルを主に
得る場合、塩基およびジメチルスルホキシドの使用量は
、２，５−チオフェンジカルボン酸ジエステルに対し、
いずれも１．５〜４．０倍モル、好ましくは２０〜４０
倍モルの範囲である。ただし、ジメチルスルホキシドに
ついては、同時に溶媒としても用いる場合にはこれを越
える量であってもよい。The amounts of base and dimethyl sulfoxide used vary depending on the purpose. That is, one ester of the 2,5-thiophenedicarboxylic acid diester is converted to (methylsulfinyl)acetyl, and the compound is converted to a compound of the general formula [wherein R represents an alkyl group having 1 to 4 carbon atoms]. ] When mainly obtaining 5-(methylsulfinyl)acetyl 2-thiophenecarboxylic acid ester represented by
Both are 1.5 to 4.0 times the mole, preferably 20 to 40
It is in the double molar range. However, if dimethyl sulfoxide is used as a solvent at the same time, the amount may exceed this amount.
一方２．５−チオフェンジカルボン酸ジエステルの両方
のエステルを（メチルスルフィニル）アセチルに変換し
、式（■）′
て表される２、５−ビス−（メチルスルフィニル）アセ
チルチオフェンを主に得る場合、塩基およびジメチルス
ルホキシドの使用量は、いずれも２゜５−チオフェンジ
カルボン酸ジエステルに対し３０〜８．０倍モル、好ま
しくは５．０〜７０倍モルの範囲である。ただし、ジメ
チルスルホキシドについては、前記の５−（メチルスル
フィニル）アセチル−２−チオフェンカルボン酸エステ
ルを主に得る場合と同様に、同時に溶媒としても用いる
場合にはこれを越える量であってもよい。On the other hand, when both esters of 2,5-thiophenedicarboxylic acid diester are converted to (methylsulfinyl)acetyl to mainly obtain 2,5-bis-(methylsulfinyl)acetylthiophene represented by the formula (■)', The amount of base and dimethyl sulfoxide to be used is in the range of 30 to 8.0 times, preferably 5.0 to 70 times, by mole relative to the 2.sup.5-thiophenedicarboxylic acid diester. However, the amount of dimethyl sulfoxide may exceed this amount when it is used simultaneously as a solvent, as in the case where the 5-(methylsulfinyl)acetyl-2-thiophenecarboxylic acid ester is mainly obtained.
反応溶媒としては、前述の通り反応試剤であるジメチル
スルホキシドをそのまま用いることもてきるが、本反応
において不活性である限りは特に限定されるものてはな
く、例えば、テトラヒドロフラン、ジオキサン等のエー
テル類、ジクロルエタン、クロロホルム、四塩化炭素、
クロロベンゼン等のハロゲン化炭化水素類、ベンゼン、
トルエン、キシレン等の芳香族炭化水素類等を使用する
ことかてきる。当該溶媒としては、後処理の容易な点か
らクロロベンゼン、トルエン等を使用するのか好ましい
。溶媒の使用量は、原料の２，５−チオフェンジカルボ
ン酸ジエステルの重量に対し、通常３〜２０倍量である
。As the reaction solvent, dimethyl sulfoxide, which is a reaction reagent as described above, can be used as it is, but it is not particularly limited as long as it is inactive in this reaction. For example, ethers such as tetrahydrofuran and dioxane can be used. , dichloroethane, chloroform, carbon tetrachloride,
Halogenated hydrocarbons such as chlorobenzene, benzene,
Aromatic hydrocarbons such as toluene and xylene can be used. As the solvent, it is preferable to use chlorobenzene, toluene, etc. from the viewpoint of easy post-treatment. The amount of the solvent used is usually 3 to 20 times the weight of the 2,5-thiophenedicarboxylic acid diester as the raw material.
反応温度は、通常２０°Ｃ〜８０°Ｃの範囲てあり好ま
しくは３０°Ｃ〜６０°Ｃの範囲である。反応温度か８
０’Ｃよりも高いときは副反応かおこり、他方、反応温
度か２０°Ｃよりも低いときは反応速度か実用上遅すぎ
るので好ましくない。The reaction temperature is usually in the range of 20°C to 80°C, preferably in the range of 30°C to 60°C. Reaction temperature 8
When the reaction temperature is higher than 0'C, side reactions occur, whereas when the reaction temperature is lower than 20C, the reaction rate is too slow for practical use, which is not preferable.
反応時間は、反応温度により一概には言えないか、通常
１〜２４時間の範囲である。The reaction time cannot be determined unconditionally depending on the reaction temperature, but is usually in the range of 1 to 24 hours.
上述のようにして得られた反応液は、通常、水で希釈後
適当な抽出溶媒により生成した（メチルスルフィニル）
アセチルチオフェン誘導体を抽出した後、還元して目的
とするアセチルチオフェン誘導体に変換することかでき
る。The reaction solution obtained as described above is usually diluted with water and then extracted with an appropriate extraction solvent (methylsulfinyl).
After the acetylthiophene derivative is extracted, it can be converted into the desired acetylthiophene derivative by reduction.
還元には通常、還元剤を用いることかでき、還元剤とし
ては、特に限定されるものではないか亜鉛、スズ等の金
属と塩酸、硫酸等の鉱酸あるいは、酢酸、プロピオン酸
等の有機酸の系を好適に用いることかできる。Usually, a reducing agent can be used for reduction, and the reducing agent is not particularly limited. Metals such as zinc and tin, mineral acids such as hydrochloric acid and sulfuric acid, or organic acids such as acetic acid and propionic acid are used as reducing agents. The system can be suitably used.
反応溶媒としては、特に限定されるものではないか、水
とメタノール、エタノール等のアルコール類、酢酸、プ
ロピオン酸等の有機酸、テトラヒドロフラン、ジオキサ
ン等のエーテル類、ジクロルエタン、クロロホルム、ク
ロルベンゼン等のハロゲン化炭化水素類、ベンゼン、ト
ルエン、キシレン等の芳香族化合物類等およびこれらの
２種類以上の混合物を挙げることかできる。当該溶媒と
しては、収率、操作性等の点から水、アルコールの系を
使用するのか好ましい。溶媒の使用量は、原料である２
、５−チオフェンジカルボン酸ジエステルの重量に対し
、通常３〜２０倍量である。Reaction solvents are not particularly limited, and include water and alcohols such as methanol and ethanol, organic acids such as acetic acid and propionic acid, ethers such as tetrahydrofuran and dioxane, and halogens such as dichloroethane, chloroform, and chlorobenzene. Examples include hydrogenated hydrocarbons, aromatic compounds such as benzene, toluene, and xylene, and mixtures of two or more thereof. As the solvent, water and alcohol are preferably used from the viewpoint of yield, operability, etc. The amount of solvent used is the raw material2
, the amount is usually 3 to 20 times the weight of the 5-thiophene dicarboxylic acid diester.
還元の反応温度は、通常０°Ｃ〜１００°Ｃの範囲、好
ましくは２０°Ｃ〜５０°Ｃの範囲である。反応温度か
１００°Ｃよりも高い時は副反応かおこり、他方、反応
温度が０°Ｃよりも低い時は反応速度か実用上遅すぎる
ので好ましくない。The reaction temperature for reduction is usually in the range of 0°C to 100°C, preferably in the range of 20°C to 50°C. When the reaction temperature is higher than 100°C, side reactions occur, whereas when the reaction temperature is lower than 0°C, the reaction rate is too slow for practical use, which is not preferred.
還元の反応時間は、反応温度により一概には言えないか
、通常１〜２４時間の範囲である。The reaction time for reduction cannot be determined unconditionally depending on the reaction temperature, but is usually in the range of 1 to 24 hours.
このようにして得られるアセチルチオフェン誘導体は、
通常の後処理、例えばエーテル抽出後、晶析することに
より単離することかてきる。The acetylthiophene derivative obtained in this way is
Isolation can be achieved by conventional post-treatments, such as ether extraction followed by crystallization.
［発明の効果］
本発明のアセチルチオフェン誘導体の製造方法によＩへ
医薬、農薬等の製造のための重要な中間体として広く用
いることのできる５−アセチル−２−チオフェンカルボ
ン酸エステル及び２，５−ノアセチルチオフェンを短い
工程数で容易にかつ高収率で製造することができ、経済
的にも有利である。[Effects of the Invention] The method for producing acetylthiophene derivatives of the present invention produces 5-acetyl-2-thiophenecarboxylic acid ester and 2, which can be widely used as an important intermediate for producing pharmaceuticals, agricultural chemicals, etc. 5-Noacetylthiophene can be easily produced with a high yield in a short number of steps, and is economically advantageous.
［実施例］
以下に実施例を挙げて本発明を具体的に説明するが、本
発明はこれらの実施例により何ら限定されるものではな
い。[Examples] The present invention will be specifically described below with reference to Examples, but the present invention is not limited to these Examples in any way.
製造例１
２．５−チオフェンジカルボン酸ジメチルエステルの製
造
攪拌機、温度計、滴下ロートおよび冷却器を備えた３０
０ｍｊ容ｊｉ：４ツロフラスコにα、α° −ジブロモ
アジピン酸ジメチルエステル３３２ｇ（０，１０モル）
、クロルベンセン１０（ｈｙ！’および相間移動触媒と
してペンサルコニウムクロライド（Ｃ，４８０％以上）
０．３ｇを仕込み、攪拌下これに６０％市販硫化ナトリ
ウム１３．６５ｇ（０，１，０５モル）を水１００ｍ１
に溶解した溶液を４０°Ｃ〜５０°Ｃの範囲て１時間を
要して滴下し、さらに同温度で２時間攪拌した。その後
分液し、クロルベンゼン溶液を水洗、乾燥し、テトラヒ
ドロチオフェン−２，５−ジカルボン酸ジメチルエステ
ルのクロルベンゼン溶液を得た。引き続き一１０°Ｃ〜
−５°Ｃにて塩素１４．９ｇ（０，２１モル）を１時間
で導入した。その後同温度て１時間熟成し、塩素化反応
を行なった。添加剤として、メタノール３５ｇを加え、
８０°Ｃにて６時間攪拌し、脱塩化水素反応を行なった
。Production Example 1 Production of 2.5-thiophenedicarboxylic acid dimethyl ester
0 mj volume ji: 332 g (0.10 mol) of α,α°-dibromoadipate dimethyl ester in 4 tube flasks
, chlorobenzene 10 (hy!') and pensalkonium chloride (C, more than 480%) as a phase transfer catalyst.
13.65 g (0.1.05 mol) of 60% commercially available sodium sulfide was added to 100 ml of water while stirring.
was added dropwise over a period of 1 hour at a temperature of 40°C to 50°C, and further stirred at the same temperature for 2 hours. Thereafter, the layers were separated, and the chlorobenzene solution was washed with water and dried to obtain a chlorobenzene solution of dimethyl tetrahydrothiophene-2,5-dicarboxylic acid. Continue to -10°C
At -5 DEG C., 14.9 g (0.21 mol) of chlorine were introduced in 1 hour. Thereafter, the mixture was aged at the same temperature for 1 hour to carry out a chlorination reaction. Add 35g of methanol as an additive,
The mixture was stirred at 80°C for 6 hours to carry out a dehydrochlorination reaction.
反応終了後、反応液を冷却し、析出した結晶を濾過、洗
浄、乾燥し、２，５−チオフェンジカルボン酸ジメチル
エステル１３．２ｇ を得た。αα′ −ジブロモア
ジピン酸ジメチルエステルに対する収率は６６．０％で
あった。After the reaction was completed, the reaction solution was cooled, and the precipitated crystals were filtered, washed, and dried to obtain 13.2 g of 2,5-thiophenedicarboxylic acid dimethyl ester. The yield based on αα′-dibromoadipate dimethyl ester was 66.0%.
実施例１
攪拌機、温度計、冷却管を備えた３００ｍ１４つロフラ
スコに窒素ガスを通じつつ６０％水素化ナトリウム８．
０ｇ （０，２０モル）、ジメチルスルホキシドは溶媒
をかねて７０ｇ（０，９０モル）を仕込み、攪拌下、２
，５−チオフェンジカルボン酸ジメチルエステル２０．
０ｇ（０，１０モル）を溶解したジメチルスルホキシド
溶液９０ｇを室温にて３０分を要して滴下し、さらに４
５〜５０°Ｃで２時間攪拌した。この間窒素ガスを通じ
た。その後ジメチルスルホキシドを留去した。Example 1 60% sodium hydride was added to a 300 m 14-bottle flask equipped with a stirrer, a thermometer, and a condenser while passing nitrogen gas.8.
0 g (0.20 mol) and 70 g (0.90 mol) of dimethyl sulfoxide as a solvent were added, and while stirring, 2
, 5-thiophenedicarboxylic acid dimethyl ester20.
90 g of dimethyl sulfoxide solution in which 0 g (0.10 mol) was dissolved was added dropwise at room temperature over 30 minutes, and
Stirred at 5-50°C for 2 hours. During this time, nitrogen gas was passed through. Thereafter, dimethyl sulfoxide was distilled off.
次に得られた粗５−（メチルスルフィニル）アセチル−
２−チオフェンカルボン酸メチルエステルのナトリウム
塩に水１００ｇ、エタノール５０ｇ、および亜鉛３５ｇ
を加え、２０〜３０°Ｃの範囲て酢酸５５ｇを加え、さ
らに同温度で１時間攪拌した。The crude 5-(methylsulfinyl)acetyl-
100 g of water, 50 g of ethanol, and 35 g of zinc to the sodium salt of 2-thiophenecarboxylic acid methyl ester.
was added, and 55 g of acetic acid was added at a temperature of 20 to 30°C, followed by further stirring at the same temperature for 1 hour.
その後、固形物をろ過し、ろ液からエタノールを減圧留
去し、残留物を水で希釈した。次に、固形炭酸ナトリウ
ムで中和液生成物をエーテルで抽出した。さらに水洗浄
、乾燥後エーテルを留去し、目的とする５−アセチル−
２−チオフェンカルボン酸メチルエステル１１．３ｇを
得た。２，５−チオフェンジカルボン酸ジメチルエステ
ルに対する収率は６１．４％であった。Thereafter, the solid matter was filtered, ethanol was distilled off from the filtrate under reduced pressure, and the residue was diluted with water. The neutralized solution product with solid sodium carbonate was then extracted with ether. After further washing with water and drying, the ether is distilled off to obtain the desired 5-acetyl-
11.3 g of 2-thiophenecarboxylic acid methyl ester was obtained. The yield based on 2,5-thiophenedicarboxylic acid dimethyl ester was 61.4%.
実施例２
実施例１において６０％水素化ナトリウム２２０ｇ（０
，５５モル）、亜鉛７０ｇ、酢酸１００ｇを使用した以
外は、実施例１と同様の操作を行い、２，５−ジアセチ
ルチオフェン８．７ｇを得た。２．５−チオフェンジカ
ルボン酸ジメチルエステルに対する収率は５１．８％で
あった。Example 2 In Example 1, 220 g of 60% sodium hydride (0
, 55 mol), 70 g of zinc, and 100 g of acetic acid, the same operation as in Example 1 was performed to obtain 8.7 g of 2,5-diacetylthiophene. The yield based on 2.5-thiophenedicarboxylic acid dimethyl ester was 51.8%.
実施例３
実施例１において２，５−チオフェンジカルボン酸ジメ
チルエステルの代わりに、２．５−チオフェンジカルボ
ン酸ジエチルエステル２２．８ｇ（０，１０モル）を用
いた以外は実施例１と同様の操作を行ない、５−アセチ
ル−２−チオフェンカルボン酸エチルエステル１０．４
ｇを得た。２゜５−チオフェンジカルボン酸ジエチルエ
ステルに対する収率は５２．５％であった。Example 3 The same operation as in Example 1 except that 22.8 g (0.10 mol) of 2,5-thiophenedicarboxylic acid diethyl ester was used instead of 2,5-thiophenedicarboxylic acid dimethyl ester in Example 1. 5-acetyl-2-thiophenecarboxylic acid ethyl ester 10.4
I got g. The yield based on 2°5-thiophenedicarboxylic acid diethyl ester was 52.5%.
Claims (3)
ルに塩基の存在下でジメチルスルホキシドを反応させ、 一般式（II） ▲数式、化学式、表等があります▼（II） 〔式中、Ｙは−ＯＲまたは−ＣＨ＿２ＳＯＣＨ＿３、Ｒ
は炭素数１〜４のアルキル基を示す。〕で表わされる（
メチルスルフィニル）アセチルチオフェン誘導体を得、
次いで還元することを特徴とする、一般式（III） ▲数式、化学式、表等があります▼（III） 〔式中、Ｚは−ＯＲまたは−ＣＨ＿３、Ｒは炭素数１〜
４のアルキル基を示す。〕 で表わされるアセチルチオフェン誘導体の製造方法。(1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R represents an alkyl group having 1 to 4 carbon atoms. ] The 2,5-thiophenedicarboxylic acid diester represented by is reacted with dimethyl sulfoxide in the presence of a base to form the general formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) [In the formula, Y is -OR or -CH_2SOCH_3,R
represents an alkyl group having 1 to 4 carbon atoms. ] is represented by (
methylsulfinyl) acetylthiophene derivative,
General formula (III), which is characterized by subsequent reduction ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) [In the formula, Z is -OR or -CH_3, R is a carbon number of 1 to
4 shows the alkyl group. ] A method for producing an acetylthiophene derivative represented by:
載の製造方法。(2) The manufacturing method according to claim (1), wherein the base is an alkali metal hydride.
求項（２）記載の製造方法。(3) The production method according to claim (2), wherein the alkali metal hydride is sodium hydride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27446990A JPH04149179A (en) | 1990-10-11 | 1990-10-11 | Production of acetylthiophene derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27446990A JPH04149179A (en) | 1990-10-11 | 1990-10-11 | Production of acetylthiophene derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04149179A true JPH04149179A (en) | 1992-05-22 |
Family
ID=17542129
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP27446990A Pending JPH04149179A (en) | 1990-10-11 | 1990-10-11 | Production of acetylthiophene derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04149179A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN121471196A (en) * | 2026-01-08 | 2026-02-06 | 济南国鼎医药科技有限公司 | A method for preparing an intermediate of aprolol hydrochloride |
-
1990
- 1990-10-11 JP JP27446990A patent/JPH04149179A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN121471196A (en) * | 2026-01-08 | 2026-02-06 | 济南国鼎医药科技有限公司 | A method for preparing an intermediate of aprolol hydrochloride |
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