JPH0222072B2 - - Google Patents
Info
- Publication number
- JPH0222072B2 JPH0222072B2 JP14607481A JP14607481A JPH0222072B2 JP H0222072 B2 JPH0222072 B2 JP H0222072B2 JP 14607481 A JP14607481 A JP 14607481A JP 14607481 A JP14607481 A JP 14607481A JP H0222072 B2 JPH0222072 B2 JP H0222072B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- substituted
- formula
- alkyl group
- lower alkyl
- 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
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 19
- -1 ammonium halide Chemical class 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 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 claims description 4
- 238000006722 reduction reaction Methods 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 150000003577 thiophenes Chemical class 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000003158 alcohol group Chemical group 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 238000006027 Birch reduction reaction Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- CRLIPFLHAFJSSU-UHFFFAOYSA-N 1-(5-butylthiophen-2-yl)butan-1-one Chemical compound C(CCC)(=O)C=1SC(=CC1)CCCC CRLIPFLHAFJSSU-UHFFFAOYSA-N 0.000 description 2
- WURYWHAKEJHAOV-UHFFFAOYSA-N 2,5-dihydrothiophene Chemical class C1SCC=C1 WURYWHAKEJHAOV-UHFFFAOYSA-N 0.000 description 2
- MNDZHERKKXUTOE-UHFFFAOYSA-N 2-butylthiophene Chemical compound CCCCC1=CC=CS1 MNDZHERKKXUTOE-UHFFFAOYSA-N 0.000 description 2
- 229910000497 Amalgam Inorganic materials 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000002917 insecticide Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 1
- YXHIINNJOGKPLF-UHFFFAOYSA-N 1-(2-Thienyl)-1-butanone Chemical compound CCCC(=O)C1=CC=CS1 YXHIINNJOGKPLF-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LHQVLWPLUAXGTE-UHFFFAOYSA-N CCCCCCCC(C=CC=CC)=O Chemical compound CCCCCCCC(C=CC=CC)=O LHQVLWPLUAXGTE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003898 horticulture Methods 0.000 description 1
- 229960002523 mercuric chloride Drugs 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- DWXYESOTAHVYEC-UHFFFAOYSA-N octa-5,7-dien-4-one Chemical compound CCCC(=O)C=CC=C DWXYESOTAHVYEC-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
Landscapes
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
本発明は、カロチノイド類及びプロスタグラン
ジン類などの製造に有用な例えば、５，７―オク
タジエン―４―オン又は９，11―トリデカジエン
―８―オンなどの合成中間体として有用であり、
更に、それ自体で生理活性を示し、医薬、農園芸
分野などにおいて、殺菌、殺虫剤として有用性の
期待される従来文献未記載の２，２―ジ置換―５
―未置換−又は２，２―ジ置換―５―アルキル置
換―２，５―ジヒドロチオフエン類及びその製法
に関する。
更に詳しくは、本発明は、下記式（）、
但し式中、R1はアルキル基好ましくはC1〜C12
アルキル基、ハロゲン置換されていてもよいシク
ロヘキシル基及び水酸基よりなる群からえらばら
れた基を示し、R2は水素原子及び低級アルキル
基好ましくはC1〜C4アルキル基よりなる群から
えらばれた基を示し、R3は飽和もしくは不飽和
の低級アルキル基好ましくはC1〜C4アルキル基、
低級アルキル基で置換されていてもよいベンジル
基よりなる群からえらばれた基を示す。
で表わされる２，２―ジ置換―５―未置換−又は
２，２―ジ置換―５―アルキル置換―２，５―ジ
ヒドロチオフエン類及びその製法に関する。
本発明者等は、２―置換カルボニル―チオフエ
ン類のバーチ（Birch）還元について研究を行つ
てきたが、今回、前記式（）で示すことのでき
る従来文献未記載の２，２―ジ置換―５―未置換
―又は２，２―ジ置換基―５―アルキル置換―
２，５―ジヒドロチオフエン類が存在でき且つ容
易な手段で合成できることを発見した。更に、該
式（）化合物は前記合成中間体として、又、生
理活性化合物としての有用な化合物であることを
知つた。
従つて、本発明の目的は、上記式（）化合物
を提供するにある。本発明の他の目的は、上記式
（）化合物の製法を提供するにある。
本発明の上記諸目的及び更に多くの他の目的な
らびに利点は、以下の記載から一層明らかとなる
であろう。
前記式（）化合物のR1中、アルキルの例と
しては、メチル、エチル、プロピル（ｎ―，iso
―）、ブチル（ｎ―，iso―，sec―tert―）、ヘプ
チル、オクチル、ノニルなどのC1〜C12アルキル
基を好ましく例示できる。又ハロゲン置換されて
いてもよいシクロヘキシル基及び水酸基の例とし
ては、ハロゲン原子たとえばクロルでモノ―もし
くはジ―置換されていてもよいシクロヘキシル及
び水酸基がある。R2中、低級アルキル基の例と
しては、メチル、エチル、プロピル、ブチルが好
ましく例示できる。R3中、飽和もしくは不飽和
の低級アルキル基の例としてはメチル、エチル、
プロピル、ブチル、アリル、ブテニル（１―、２
―、３―）などが例示できる。又低級アルキル基
で置換されていてもよいベンジル基としてはモノ
―、ジ―置換ベンジル、
（
The present invention is useful as a synthetic intermediate, such as 5,7-octadien-4-one or 9,11-tridecadien-8-one, which is useful in the production of carotenoids and prostaglandins, etc.
Furthermore, 2,2-di-substituted-5, which has not been described in the literature, is expected to be useful as a bactericidal and insecticide in the fields of medicine, agriculture, horticulture, etc., as it exhibits physiological activity by itself.
-Unsubstituted- or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophenes and their production method. More specifically, the present invention provides the following formula (), However, in the formula, R 1 is an alkyl group, preferably C 1 to C 12
It represents a group selected from the group consisting of an alkyl group, a cyclohexyl group which may be substituted with halogen, and a hydroxyl group, and R 2 is a hydrogen atom and a lower alkyl group, preferably selected from the group consisting of a C 1 -C 4 alkyl group. R3 is a saturated or unsaturated lower alkyl group, preferably a C1 to C4 alkyl group,
Indicates a group selected from the group consisting of a benzyl group optionally substituted with a lower alkyl group. The present invention relates to 2,2-disubstituted-5-unsubstituted or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophenes represented by the formula and a method for producing the same. The present inventors have been conducting research on the Birch reduction of 2-substituted carbonyl-thiophenes, and this time, we have investigated the Birch reduction of 2-substituted carbonyl-thiophenes. 5-Unsubstituted- or 2,2-di-substituted-5-alkyl substituted-
It has been discovered that 2,5-dihydrothiophenes can exist and can be synthesized by easy means. Furthermore, it has been found that the compound of formula () is a useful compound as the synthetic intermediate and as a physiologically active compound. Therefore, it is an object of the present invention to provide compounds of the above formula (). Another object of the present invention is to provide a method for producing the compound of formula () above. The above objects and many other objects and advantages of the present invention will become more apparent from the following description. Examples of alkyl in R 1 of the compound of formula () are methyl, ethyl, propyl (n-, iso
-), butyl (n-, iso-, sec-tert-), heptyl, octyl, nonyl and other C 1 -C 12 alkyl groups are preferred examples. Examples of the cyclohexyl group and hydroxyl group which may be substituted with halogen include cyclohexyl and hydroxyl groups which may be mono- or di-substituted with a halogen atom, such as chloro. Preferred examples of the lower alkyl group in R 2 include methyl, ethyl, propyl, and butyl. Examples of saturated or unsaturated lower alkyl groups in R3 include methyl, ethyl,
Propyl, butyl, allyl, butenyl (1-, 2
--, 3-), etc. can be exemplified. Furthermore, examples of the benzyl group which may be substituted with a lower alkyl group include mono-, di-substituted benzyl,
(
【式】ＸおよびＹは、夫々、
水素原子又は低級アルキル基たとえばC1〜C4ア
ルキル基を示す）或いは未置換ベンジル基を例示
できる。
前記式（）化合物は、例えば、下記式に示す
ようにして製造することができる。。
上記式に於て、R1、R2及びR3は式（）及び
式（）についてすでに定義し且つ例示したと同
義である。又、式（）の５―置換もしくは未置
換チオフイン及び式（）化合物は公知化合物で
あるが、式（）中、５―置換チオフエンは、例
えば、下記式
に従つて２―アシル―チオフエンを亜鉛アマルガ
ムで塩酸々性下に加熱還流して得ることができ
る。
上記式（）で表わされる２―アシルチオフエ
ンは、例えば、J.R.Johnson、G.E.May，Org.
Synth.Coll.Vol.２，８（1943）の方法に従つて合
成できる。
例えば、無水ベンゼン200mlにチオフエン0.2モ
ルと塩化アセチル0.2モルを加え、０℃に冷却し、
塩化第二スズ0.2モルを除々に添加した後、室温
で１時間撹拌し、３％塩酸100mlを加えた後、ベ
ンゼンで抽出し、分液、無水塩化カルシウムで脱
水した後、減圧下に蒸留することにより、２―ア
セチルチオフエン（沸点は97〜98℃／16mmHg）
を好収率で得ることができる。
本発明方法によれば、例えば、上述のようにし
て形成できる下記式（）、
但し式中、R1及びR2は式（）において述べ
たと同義である。
で表わされる２―置換カルボニル―５―未置換―
又は２―置換―５―アルキル置換―チオフエン類
を、有機溶媒中で、液体アンモニア及び金属ナト
リウムの共存下に還元（バーチ還元）反応せし
め、生成物をアンモニウムハライドで処理したの
ち、ハロゲン化アルキルもしくは低級アルキル基
で置換されていてもよいハロゲン化ベンジルと反
応せしめることにより、前記式（）目的化合物
を得ることができる。
上記溶媒の例としては、メタノール、エタノー
ル、プロパノール、ブタノールなどの如き低級ア
ルコール類、エチルエーテル、テトラヒドロフラ
ンなどの如きエーテル類、及びこれらの適宜な混
合溶媒を例示することができ、これらは無水状態
で利用するのがよい。
還元反応は、上記例示の如き溶媒中、液体アン
モニアの還流条件下たとえば約−30゜〜約−35℃
で行うことができる。反応に利用する液体アンモ
ニアの使用量は適宜に選択できるが、例えば、式
（）化合物に基いて約100〜約250倍モル、より
好ましくは約150〜約200倍モルの如き使用量を例
示できる。又、金属ナトリウムの使用量も適宜に
選択でき、例えば、式（）化合物に基いて約２
〜約３倍モル、より好ましくは約2.2〜約2.4倍モ
ルの如き使用量を例示することができる。
還元反応後、反応生成物を取り出すことなし
に、連続してアルキル化もしくはベンジル化反応
を行うことができる。反応は生成物をアンモニウ
ムハライドたとえば塩化アンモニウムで処理した
のち、ハロゲン化アルキルもしくは低級アルキル
基で置換されていてもよいハロゲン化ベンジル、
例えば、臭化アルキル、臭化ベンジルと反応せし
めることにより行うことができる。反応は、生成
物系にアンモニウムハライドを添加撹拌したの
ち、上記例示の如きハロゲン化アルキルもしくは
ハロゲン化ベンジルを添加して、液体アンモニア
の還流条件下で行うことができる。アンモニウム
ハライドの使用量は適宜に選択でき、例えば、式
（）化合物に基いて約１〜約２倍モル、より好
ましくは約1.1〜約1.3倍モルの如き使用量を例示
できる。又、ハロゲン化アルキルもしくはハロゲ
ン化ベンジルの使用量としては、式（）化合物
に基いて約2.5〜約５倍モル、より好ましくは約
３〜約3.5倍モルの使用量を例示できる。
本発明によれば、上述の如き方法によつて、式
（）化合物から式（）目的化合物を得ること
ができる。得られた式（）化合物は、同一出願
人の同日付出願に係わる発明の名称“２，２―ジ
置換―５―未置換―又は２，２―ジ置換―５―ア
ルキル置換―２，５―ジヒドロチオ―フエン―
１，１―ジオキシド類及びその製法”に用いる中
間体としても有用であり、更に、それ自体、生理
活性物質として医薬、農薬などにおいて、殺菌、
殺虫剤として有用性が期待される。
以下、実施例により本発明の数態様について、
更に詳しく説明する。
実施例 １
２―アセチル―２―ベンジル―２，５―ジヒド
ロチオフエンの合成：
約100mlの液体アンモニアに２―アセチルチオ
フエン2.52ｇ（20ミリモル）とエタノール４ml、
エーテル３mlを加え、これに金属ナトリウム1.06
ｇ（46ミリモル）の細片を30〜40分で添加してバ
ーチ還元を行う。更に60分間撹拌した後、塩化ア
ンモニウム1.3ｇを加え、30分間よく撹拌する。
次に臭化ベンジル5.0ml（66.7ミリモル）を加え、
60分間撹拌しながら反応を完結させる。上記反応
は全べて液体アンモニア還流温度（−30〜−35
℃）下に実施される。
反応終了後、アンモニアを蒸発した後、10％塩
酸で処理し、エーテルで抽出後、炭酸水素ナトリ
ウムで中和する。エーテル溶液を無水芒硝で脱水
した後、カラムクロマトグラフイーにより２―ア
セチル―２―ベンジル―２，５―ジヒドロチオフ
エンを単離した。その収率は73％である。
この物質のIR，MS，NMR及び元素分析値は
表１に示した。
実施例 ２
２―ブチリル―２―ベンジル―５―ブチル―
２，５―ジヒドロチオフエンの合成：
２―ブチリルチオフエン（b.p.111〜112℃／13
mmHg）23.1ｇ（0.15モル）と亜鉛アマルガム（金
属亜鉛100ｇ、塩化第二水銀2.0ｇ、より調製し、
水洗したもの）とを水100ml、濃塩酸100ml中で、
20時間煮沸還流した後、ベンゼンで抽出し、水で
洗浄した後、無水芒硝で乾燥する。溶媒を除去
し、減圧下に蒸留する。b.p.73〜80℃／20mmHg
の５―ブチルチオフエンが得られる。この５―ブ
チルチオフエンをJ.R.Johnson，G.E.May，Org.
Synth.Coll.Vol.２，８（1943）の２―アセチルチ
オフエンの合成方法に従つて、２―ブチリル―５
―ブチルチオフエン（b.p.113〜114℃／４mmHg）
を得た。
２―ブチリル―５―ブチルチオフエン4.20ｇ
（20ミリモル）を用いるほかは実施例１と同様に
して、２―ブチリル―２―ベンジル―５―ブチル
―２，５―ジヒドロチオフエンが76％の好収率で
得られる。その分析値は表１に示した。
表１には、種々の他の式（）加合物を用い
て、同様にして、種々の式（）化合物を合成し
た結果を一緒に示してある。[Formula] X and Y each represent a hydrogen atom, a lower alkyl group (eg, a C 1 -C 4 alkyl group), or an unsubstituted benzyl group. The compound of formula () can be produced, for example, as shown in the following formula. . In the above formula, R 1 , R 2 and R 3 have the same meanings as those already defined and exemplified for formula () and formula (). Furthermore, 5-substituted or unsubstituted thiophene of formula () and compounds of formula () are known compounds, but in formula (), 5-substituted thiophene is, for example, represented by the following formula: Accordingly, 2-acyl-thiophene can be obtained by heating and refluxing a zinc amalgam under hydrochloric acid. The 2-acylthiophene represented by the above formula () can be obtained from, for example, JR Johnson, GE May, Org.
It can be synthesized according to the method of Synth.Coll.Vol. 2 , 8 (1943). For example, add 0.2 mol of thiophene and 0.2 mol of acetyl chloride to 200 ml of anhydrous benzene, cool it to 0°C,
After gradually adding 0.2 mol of stannic chloride, stir at room temperature for 1 hour, add 100 ml of 3% hydrochloric acid, extract with benzene, separate the mixture, dehydrate with anhydrous calcium chloride, and distill under reduced pressure. 2-acetylthiophene (boiling point 97-98℃/16mmHg)
can be obtained in good yield. According to the method of the present invention, for example, the following formula (), which can be formed as described above, However, in the formula, R 1 and R 2 have the same meaning as stated in the formula (). 2-substituted carbonyl-5-unsubstituted-
Alternatively, a 2-substituted-5-alkyl-substituted thiophene is subjected to a reduction reaction (Birch reduction) in the presence of liquid ammonia and metallic sodium in an organic solvent, and the product is treated with ammonium halide. By reacting with a halogenated benzyl which may be substituted with a lower alkyl group, the target compound of the formula () can be obtained. Examples of the above-mentioned solvent include lower alcohols such as methanol, ethanol, propanol, and butanol, ethers such as ethyl ether, and tetrahydrofuran, and appropriate mixed solvents thereof, which are used in an anhydrous state. It is good to use it. The reduction reaction is carried out in a solvent such as those exemplified above under refluxing conditions of liquid ammonia, for example, at about -30° to about -35°C.
It can be done with The amount of liquid ammonia used in the reaction can be selected as appropriate, and for example, the amount used may be about 100 to about 250 times the molar amount, more preferably about 150 to about 200 times the molar amount, based on the compound of formula (). . In addition, the amount of metal sodium to be used can be selected as appropriate, for example, about 2% based on the compound of formula ().
Examples of the usage amount include about 3 times the mole, more preferably about 2.2 to about 2.4 times the mole. After the reduction reaction, an alkylation or benzylation reaction can be carried out continuously without taking out the reaction product. The reaction is carried out by treating the product with an ammonium halide such as ammonium chloride, followed by a benzyl halide optionally substituted with an alkyl halide or a lower alkyl group,
For example, it can be carried out by reacting with alkyl bromide or benzyl bromide. The reaction can be carried out under refluxing conditions of liquid ammonia by adding and stirring ammonium halide to the product system, then adding an alkyl halide or benzyl halide such as those exemplified above. The amount of ammonium halide to be used can be appropriately selected, for example, about 1 to about 2 moles, more preferably about 1.1 to about 1.3 moles, based on the compound of formula (). The amount of the alkyl halide or benzyl halide to be used is, for example, about 2.5 to about 5 times the mole, more preferably about 3 to about 3.5 times the mole based on the compound of formula (). According to the present invention, a target compound of formula () can be obtained from a compound of formula () by the method described above. The obtained compound of formula () has the title of the invention “2,2-disubstituted-5-unsubstituted- or 2,2-disubstituted-5-alkyl-substituted-2,5” filed by the same applicant on the same date. -dihydrothio-phene-
It is also useful as an intermediate used in 1,1-dioxides and their production methods, and is also used as a physiologically active substance in medicines, agricultural chemicals, etc. for sterilization,
It is expected to be useful as an insecticide. Hereinafter, some embodiments of the present invention will be described with reference to Examples.
It will be explained in more detail. Example 1 Synthesis of 2-acetyl-2-benzyl-2,5-dihydrothiophene: 2.52 g (20 mmol) of 2-acetylthiophene and 4 ml of ethanol in about 100 ml of liquid ammonia,
Add 3 ml of ether and add 1.06 ml of metallic sodium to this.
Birch reduction is carried out by adding g (46 mmol) of strips over 30-40 minutes. After stirring for an additional 60 minutes, add 1.3 g of ammonium chloride and stir well for 30 minutes.
Next, add 5.0 ml (66.7 mmol) of benzyl bromide,
The reaction is completed with stirring for 60 minutes. All of the above reactions were carried out at liquid ammonia reflux temperature (-30 to -35
°C). After the reaction is complete, ammonia is evaporated, treated with 10% hydrochloric acid, extracted with ether, and neutralized with sodium hydrogen carbonate. After dehydrating the ether solution with anhydrous sodium sulfate, 2-acetyl-2-benzyl-2,5-dihydrothiophene was isolated by column chromatography. Its yield is 73%. The IR, MS, NMR, and elemental analysis values of this substance are shown in Table 1. Example 2 2-butyryl-2-benzyl-5-butyl-
Synthesis of 2,5-dihydrothiophene: 2-butyrylthiophene (bp111-112℃/13
mmHg) 23.1 g (0.15 mol) and zinc amalgam (metallic zinc 100 g, mercuric chloride 2.0 g,
(washed with water) in 100 ml of water and 100 ml of concentrated hydrochloric acid,
After boiling and refluxing for 20 hours, it is extracted with benzene, washed with water, and dried with anhydrous sodium sulfate. Remove the solvent and distill under reduced pressure. bp73~80℃/20mmHg
5-butylthiophene is obtained. This 5-butylthiophene was prepared by JR Johnson, GEMay, Org.
2 , 8 (1943), 2-butyryl-5
-Butylthiophene (bp113-114℃/4mmHg)
I got it. 2-butyryl-5-butylthiophene 4.20g
2-butyryl-2-benzyl-5-butyl-2,5-dihydrothiophene was obtained in a good yield of 76% in the same manner as in Example 1 except that (20 mmol) was used. The analytical values are shown in Table 1. Table 1 also shows the results of synthesizing various compounds of formula () in the same manner using various other adducts of formula ().
【表】【table】
【表】【table】
Claims (1)
れていてもよいシクロヘキシル基及び水酸基より
なる群からえらばれた基を示し、R2は水素原子
及び低級アルキル基よりなる群からえらばれた基
を示し、R3は飽和もしくは不飽和の低級アルキ
ル基及び低級アルキル基で置換されていてもよい
ベンジル基よりなる群からえらばれた基を示す、 で表わされる２，２―ジ置換―５―未置換−又は
２，２―ジ置換―５―アルキル置換―２，５―ジ
ヒドロチオフエン類。 ２ 該R1はC1〜C12アルキル基、シクロヘキシル
基及び水酸基よりなる群からえらばれた基を示
し、R2は水素原子及びC1〜C4アルキル基よりな
る群からえらばれた基を示し、R3は飽和もしく
は不飽和のC1〜C4アルキル基及びベンジル基よ
りなる群からえらばれた基を示す特許請求の範囲
第１項記載の化合物。 ３ 下記式（）、 但し式中、R1はアルキル基、ハロゲン置換さ
れていてもよいシクロヘキシル基及び水酸基より
なる群からえらばれた基を示し、R2は水素原子
及び低級アルキル基よりなる群からえらばれた基
を示す、 で表わされる２―置換カルボニル―５―未置換−
又は２―置換カルボニル―５―アルキル置換―チ
オフエン類を、有機溶媒中で、液体アンモニア及
び金属ナトリウムの共存下に還元反応せしめ、生
成物をアンモニウムハライドで処理したのち、ハ
ロゲン化アルキルもしくは低級アルキル基で置換
されていてもよいハロゲン化ベンジルと反応せし
めることを特徴とする下記式（）、 但し式中、R1はアルキル基、ハロゲン置換さ
れていてもよいシクロヘキシル基及び水酸基より
なる群からえらばれた基を示し、R2は水素原子
及び低級アルキル基よりなる群からえらばれた基
を示し、R3は飽和もしくは不飽和の低級アルキ
ル基及び低級アルキル基で置換されていてもよい
ベンジル基よりなる群からえらばれた基を示す、 で表わされる２，２―ジ置換―５―未置換−又は
２，２―ジ置換―５―アルキル置換―２，５―ジ
ヒドロチオフエン類の製法。 ４ 該有機溶媒がアルコール類、エーテル類もし
くはそれらの混合物である特許請求の範囲第３項
記載の製法。[Claims] 1. The following formula (), However, in the formula, R 1 represents a group selected from the group consisting of an alkyl group, a cyclohexyl group which may be substituted with halogen, and a hydroxyl group, and R 2 represents a group selected from the group consisting of a hydrogen atom and a lower alkyl group. and R 3 represents a group selected from the group consisting of a saturated or unsaturated lower alkyl group and a benzyl group optionally substituted with a lower alkyl group. Substituted- or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophenes. 2 R 1 represents a group selected from the group consisting of a C 1 to C 12 alkyl group, a cyclohexyl group, and a hydroxyl group, and R 2 represents a group selected from the group consisting of a hydrogen atom and a C 1 to C 4 alkyl group. The compound according to claim 1, wherein R3 represents a group selected from the group consisting of a saturated or unsaturated C1 - C4 alkyl group and a benzyl group. 3 The following formula (), However, in the formula, R 1 represents a group selected from the group consisting of an alkyl group, a cyclohexyl group which may be substituted with halogen, and a hydroxyl group, and R 2 represents a group selected from the group consisting of a hydrogen atom and a lower alkyl group. 2-substituted carbonyl-5-unsubstituted- represented by
Alternatively, a 2-substituted carbonyl-5-alkyl-substituted thiophene is subjected to a reduction reaction in an organic solvent in the coexistence of liquid ammonia and metallic sodium, and the product is treated with ammonium halide, followed by a halogenated alkyl or lower alkyl group. The following formula () is characterized by reacting with a benzyl halide which may be substituted with However, in the formula, R 1 represents a group selected from the group consisting of an alkyl group, a cyclohexyl group which may be substituted with halogen, and a hydroxyl group, and R 2 represents a group selected from the group consisting of a hydrogen atom and a lower alkyl group. and R 3 represents a group selected from the group consisting of a saturated or unsaturated lower alkyl group and a benzyl group optionally substituted with a lower alkyl group. A method for producing substituted- or 2,2-disubstituted-5-alkyl-substituted-2,5-dihydrothiophenes. 4. The manufacturing method according to claim 3, wherein the organic solvent is an alcohol, an ether, or a mixture thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14607481A JPS5849378A (en) | 1981-09-18 | 1981-09-18 | 2,2-disubstituted-5-unsubstituted- or 2,2-disubstituted-5- alkyl-substituted-2,5-dihydrothiophene and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14607481A JPS5849378A (en) | 1981-09-18 | 1981-09-18 | 2,2-disubstituted-5-unsubstituted- or 2,2-disubstituted-5- alkyl-substituted-2,5-dihydrothiophene and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5849378A JPS5849378A (en) | 1983-03-23 |
| JPH0222072B2 true JPH0222072B2 (en) | 1990-05-17 |
Family
ID=15399506
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14607481A Granted JPS5849378A (en) | 1981-09-18 | 1981-09-18 | 2,2-disubstituted-5-unsubstituted- or 2,2-disubstituted-5- alkyl-substituted-2,5-dihydrothiophene and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5849378A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4476312A (en) * | 1982-05-24 | 1984-10-09 | Pfizer Inc. | Processes for making 3-methylthiophene-2-carboxaldehyde and intermediates therefor |
| JPS62144628U (en) * | 1986-03-07 | 1987-09-11 | ||
| PT2697290T (en) * | 2011-04-11 | 2020-12-07 | Inovyn Europe Ltd | Manufacture and use of a composite material comprising fibres and at least one vinyl chloride polymer |
-
1981
- 1981-09-18 JP JP14607481A patent/JPS5849378A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5849378A (en) | 1983-03-23 |
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