JPH032861B2 - - Google Patents
Info
- Publication number
- JPH032861B2 JPH032861B2 JP63331822A JP33182288A JPH032861B2 JP H032861 B2 JPH032861 B2 JP H032861B2 JP 63331822 A JP63331822 A JP 63331822A JP 33182288 A JP33182288 A JP 33182288A JP H032861 B2 JPH032861 B2 JP H032861B2
- Authority
- JP
- Japan
- Prior art keywords
- parts
- heterocyclic
- formula
- reaction
- triphenylphosphine
- 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 - Lifetime
Links
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 14
- -1 heterocyclic thiol Chemical class 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 3
- 150000001340 alkali metals Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- SWEDAZLCYJDAGW-UHFFFAOYSA-N Thiophene-2-thiol Chemical compound SC1=CC=CS1 SWEDAZLCYJDAGW-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical compound [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- WPCNUYIIICWLKF-UHFFFAOYSA-N ethyl pyridine-2-sulfonate Chemical compound CCOS(=O)(=O)C1=CC=CC=N1 WPCNUYIIICWLKF-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【発明の詳細な説明】
本発明は含複素環チオール類の製法に係わる。
詳記すれば、式 Ａ・SO3R→SH（Ａは芳香族性
を有する複素環基を示し、Ｒは水素原子、アルカ
リ金属原子又はアルキル基を示す。）で示される
合成反応を、基質である含複素環スルホン酸類
Ａ・SO3Rに、還元助剤の存在で、トリフエニル
ホスフインを反応させて達成する、含複素環チオ
ールＡ・SHの製造法、に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing heterocyclic thiols.
Specifically, the synthesis reaction represented by the formula A・SO 3 R→SH (A represents a heterocyclic group having aromaticity, R represents a hydrogen atom, an alkali metal atom, or an alkyl group) is carried out using a substrate. The present invention relates to a method for producing a heterocycle-containing thiol A.SH, which is achieved by reacting a heterocycle-containing sulfonic acid A.SO 3 R with triphenylphosphine in the presence of a reducing agent.
含複素環チオールは医薬品その他工業的製品及
びそれらの原料、中間体として有用であるが、そ
の効果的な製法は乏しく、而も本発明方法の如く
ワン・ポツト反応で簡易に高純度の製品を、好収
率で得る方法はなかつた。 Heterocyclic thiols are useful as pharmaceuticals and other industrial products, as well as their raw materials and intermediates, but there are few effective methods for producing them, and it is difficult to easily produce high-purity products using a one-pot reaction such as the method of the present invention. There was no way to obtain it with good yield.
本発明者らは鋭意研究の結果、入手し易い基質
であり乍ら、還元反応に抵抗して原料とし難い含
複素環スルホン酸類から、有用な含複素環チオー
ルを得る新規簡易な製法を開発、本発明を完成し
た。 As a result of intensive research, the present inventors have developed a new and simple production method for obtaining useful heterocyclic thiols from heterocyclic sulfonic acids, which are easily available substrates but are difficult to use as raw materials due to their resistance to reduction reactions. The invention has been completed.
従来含複素環チオールは、製造困難な原料、例
えばリチウム化合物、むしろチオールが原料とな
るような化合物、例えばチオールエステルなどか
らの製法が知られていたり、稍々製造し易いハロ
ゲン化合物とかスルホン酸クロリドからの、扱い
難く収率低い製法が行われていたに過ぎない。 Conventionally, heterocyclic thiols have been manufactured using difficult-to-manufacture raw materials, such as lithium compounds, or compounds that use thiols as raw materials, such as thiol esters, or halogenated compounds or sulfonic acid chlorides, which are somewhat easy to manufacture. However, only a difficult-to-handle and low-yield manufacturing method was used.
本発明方法は、適当な有機溶剤中、含複素環ス
ルホン酸類Ａ・SO3Rと、トリフエニルホスフイ
ンと、還元助剤としてヨウ素とを混じて数時間、
室温〜加熱状態で反応すればよい。基質として含
複素環スルホン酸のアルカリ金属塩またはアルキ
ルエステルを選んだときは、上記反応の後、僅量
の水を添加して、更に少時加熱するという付帯処
理を施す。収量は定量的である。 The method of the present invention involves mixing heterocyclic sulfonic acids A.SO 3 R, triphenylphosphine, and iodine as a reducing agent in a suitable organic solvent for several hours.
The reaction may be carried out at room temperature to heated conditions. When an alkali metal salt or alkyl ester of a heterocyclic sulfonic acid is selected as a substrate, an additional treatment is performed after the above reaction by adding a small amount of water and further heating for a short time. Yield is quantitative.
本発明に係る含複素環スルホン酸類Ａ・SO3R
のＡとしては、ピリジンやその同族体、チオフエ
ン、ピロール、フラン等の芳香族性を有する複素
環基が挙げられる。また、Ｒとしては、水素原
子、アルカリ金属原子又はアルキル基等が挙げら
れる。 Heterocyclic sulfonic acids A・SO 3 R according to the present invention
Examples of A include aromatic heterocyclic groups such as pyridine, its homologues, thiophene, pyrrole, and furan. Moreover, examples of R include a hydrogen atom, an alkali metal atom, an alkyl group, and the like.
使用する有機溶剤は原料類を溶解し、本発明方
法条件で原料類及び成績体と反応しないなら、通
常のものが支障なく使用できる。経済的見地から
ベンゼン、トルエン、キシレン、ヘキサン、ヘプ
タンなどが好ましい。 As long as the organic solvent used dissolves the raw materials and does not react with the raw materials and the resultant under the process conditions of the present invention, ordinary organic solvents can be used without any problem. From an economic standpoint, benzene, toluene, xylene, hexane, heptane, etc. are preferred.
スルホン酸基１個について示せば、その基質１
モルに対して、トリフエニルホスフインは当量で
ある３モル〜若干過剰に使用、還元助剤は触媒と
して作用するから数量は特に規定されないが、使
用量を減らすと、反応時間が若干延びる結果とな
る。通常0.1〜１モルを使用する。 For one sulfonic acid group, its substrate 1
Based on the mole, triphenylphosphine is used in an equivalent amount of 3 moles to a slight excess.Since the reduction aid acts as a catalyst, the amount is not particularly specified, but if the amount used is reduced, the reaction time will be slightly extended. Become. Usually 0.1 to 1 mole is used.
反応終了すれば稀ハイドロサルフアイト水溶液
で洗浄後、アルカリ水溶液へ成績チオールを移し
て中和してチオールを単離、有機溶剤で抽出して
精製する。一般にチオール類は空気等によつて酸
化され易いので、不活性ガス雰囲気内で処理を終
るのが望ましい。アルカリ水溶液不溶分として回
収されるトリフエニルホスフインオキシドは、還
元してトリフエニルホスフインに再生される。 When the reaction is completed, the resulting thiol is washed with a dilute aqueous hydrosulfite solution, then transferred to an alkaline aqueous solution to neutralize it, and the thiol is isolated and purified by extraction with an organic solvent. Since thiols are generally easily oxidized by air, it is desirable to complete the treatment in an inert gas atmosphere. Triphenylphosphine oxide, which is recovered as an aqueous alkali solution insoluble matter, is reduced and regenerated into triphenylphosphine.
以下に実施例を示す。数量を表わす部は重量部
を、％は重量％を表わす。 Examples are shown below. Parts representing numbers represent parts by weight, and % represents weight %.
実施例 １
ヘプタン400部、ピリジン−２−スルホン酸エ
チル18.7部、ヨウ素8.5部、トリフエニルホスフ
イン104部を用い、50〜60℃で４時間攪拌したあ
と、水10部を加えて、１時間還流反応する。冷却
後３％ハイドロ亜硫酸ナトリウム水溶液400部で
洗浄（窒素雰囲気中）、５％水酸化ナトリウム水
溶液800部次いで200部で抽出、アルカリ抽出水溶
液を酸で中和して、分離して来る有機化合物を、
エーテルで抽出分取する。得られたエーテル溶液
を乾燥し、エーテルを溜去して得た残渣をベンゼ
ンから再結晶して、融点124〜７℃のピリジン−
２−チオール10.2部を得る。Example 1 400 parts of heptane, 18.7 parts of ethyl pyridine-2-sulfonate, 8.5 parts of iodine, and 104 parts of triphenylphosphine were stirred at 50 to 60°C for 4 hours, then 10 parts of water was added and stirred for 1 hour. Reflux reaction. After cooling, wash with 400 parts of a 3% aqueous sodium hydrosulfite solution (in a nitrogen atmosphere), extract with 800 parts and then 200 parts of a 5% aqueous sodium hydroxide solution, neutralize the alkaline extracted aqueous solution with an acid, and remove the separated organic compounds. ,
Extract and fractionate with ether. The resulting ether solution was dried, the ether was distilled off, and the resulting residue was recrystallized from benzene to give pyridine-
10.2 parts of 2-thiol are obtained.
実施例 ２
トルエン600部、チオフイン−２−スルホン酸
16.4部、ヨウ素10.2部、トリフエニルホスフイン
110部を用い、５時間攪拌還流反応したあと、実
施例１と同様にして後処理を行い、得られたエー
テル溶液を乾燥後分溜して、輜点52〜５℃（５mm
Hg）のチオフエン−２−チオール10.5部を得る。Example 2 600 parts of toluene, thiophine-2-sulfonic acid
16.4 parts, iodine 10.2 parts, triphenylphosphine
After stirring and refluxing for 5 hours using 110 parts, post-treatment was carried out in the same manner as in Example 1, and the obtained ether solution was dried and then fractionated to give a concentration point of 52 to 5°C (5 mm
10.5 parts of thiophene-2-thiol of Hg) are obtained.
Claims (1)
する複素環基を示し、Ｒは水素原子、アルカリ金
属原子又はアルキル基を示す。）で表わされる反
応に於いて、式Ａ・SO3R（式中、Ａ及びＲは前
記に同じ。）で示される含複素環スルホン酸にト
リフエニルホスフインと、ヨウ素とを反応させる
ことを特徴とする、式 Ａ・SH（式中、Ａは前記
に同じ。）で示される含複素環チオール類の製造
法。1 In the reaction represented by the formula A・SO 3 R→A・SH (A represents a heterocyclic group having aromaticity, and R represents a hydrogen atom, an alkali metal atom, or an alkyl group), the reaction of the formula A・Formula A・SH (in the formula, A and R are the same as above), which is characterized by reacting a heterocyclic sulfonic acid represented by SO 3 R (in the formula, A and R are the same as above) with triphenylphosphine and iodine. , A is the same as above.) A method for producing a heterocyclic thiol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63331822A JPH01230557A (en) | 1988-12-28 | 1988-12-28 | Production of heterocyclic ring-containing thiols |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63331822A JPH01230557A (en) | 1988-12-28 | 1988-12-28 | Production of heterocyclic ring-containing thiols |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP55137956A Division JPS5762252A (en) | 1980-10-02 | 1980-10-02 | Preparation of aromatic thiol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01230557A JPH01230557A (en) | 1989-09-14 |
| JPH032861B2 true JPH032861B2 (en) | 1991-01-17 |
Family
ID=18248028
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63331822A Granted JPH01230557A (en) | 1988-12-28 | 1988-12-28 | Production of heterocyclic ring-containing thiols |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01230557A (en) |
-
1988
- 1988-12-28 JP JP63331822A patent/JPH01230557A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01230557A (en) | 1989-09-14 |
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