DK162766B - PROCEDURE FOR THE PREPARATION OF THIOTETRONIC ACID - Google Patents
PROCEDURE FOR THE PREPARATION OF THIOTETRONIC ACID Download PDFInfo
- Publication number
- DK162766B DK162766B DK017886A DK17886A DK162766B DK 162766 B DK162766 B DK 162766B DK 017886 A DK017886 A DK 017886A DK 17886 A DK17886 A DK 17886A DK 162766 B DK162766 B DK 162766B
- Authority
- DK
- Denmark
- Prior art keywords
- acid
- thiotetronic acid
- thiotetronic
- process according
- preparation
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/32—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Epoxy Compounds (AREA)
Abstract
Description
iin
DK 162766 BDK 162766 B
Den foreliggende opfindelsen angår en særlig fremgangsmåde til fremstilling af thiotetronsyre med formlen HO— — 5 Thiotetronsyre har betydelige anvendelsesmuligheder som mellemprodukt til fremstillingen af (±) thiolactomycin, som er et bredspektret antibiotikum, jf. Tetrahedron Letters, bind 25, nr. 46, 5243-5246, 1984.The present invention relates to a particular process for the preparation of thiotetronic acid of the formula HO - 5 No. 5246, 1984.
Fra E. Benary, Chem. Berichte 46, 2 103 (1913) er det 10 kendt at fremstille thiotetronsyre ud fra acetylthio-glycoylchlorid ved omsætning med natriummalonester og efterfølgende ringslutning og behandling med vand.From E. Benary, Chem. Berichte 46, 2 103 (1913), it is known to prepare thiotetronic acid from acetylthioglycoyl chloride by reaction with sodium malone ester and subsequent cyclization and treatment with water.
D.B. Macierewicz, Rocz. Chem. 47, 1735 (1973) har udført reaktionen ifølge E. Benary og derved fremstillet thio-15 tetronsyre i et udbytte på 30,3%, beregnet på det anvendte acetylthioglycoylchlorid.D.B. Macierewicz, Rocz. Chem. 47, 1735 (1973) carried out the reaction of E. Benary, thereby producing thio-tetronic acid in a yield of 30.3%, based on the acetylthioglycoyl chloride used.
En anden mulighed er syntesen ifølge J.Z. Mortensen et al., Tetrahedron 27, 3839 (1971). Ud fra 2,4-dibromthio-phen fremstilles over tre trin ved omsætning med butyl-20 lithium og t-butylperbenzoat thiotetronsyre i et udbytte på 46,2%.Another possibility is the synthesis according to J.Z. Mortensen et al., Tetrahedron 27, 3839 (1971). From 2,4-dibromothiophene, over three steps are prepared by reaction with butyl lithium and t-butyl perbenzoate thiotetronic acid in a yield of 46.2%.
Ved alle disse kendte fremgangsmåder er udbytterne alt for beskedne til en teknisk fremgangsmåde.In all these known methods, the yields are far too modest for a technical method.
Endvidere er de kendte fremgangsmåder behæftet med de 25 ulemper, at de er omstændelige, udgangsmaterialerne er. dyre, og de anvendte reagenser er vanskelige at håndtere.Furthermore, the known methods have the drawbacks of being cumbersome, the starting materials. expensive and the reagents used are difficult to handle.
DK 162766 BDK 162766 B
22
Det er derfor formålet med den foreliggende opfindelse at tilvejebringe en fremgangsmåde til fremstilling af thiotetronsyre, som udmærker sig ved høje udbytter og høj 5 renhed af thiotetronsyren, gunstige udgangsmaterialer og enkel fremgangsmådegennemførelse.It is therefore the object of the present invention to provide a process for producing thiotetronic acid which is distinguished by high yields and high purity of the thiotetronic acid, favorable starting materials and simple process execution.
Dette opnås ved fremgangsmåden ifølge opfindelsen ved, at man omsætter 4-chlor—4-chlormethyloxetan-2-on med .formlenThis is achieved by the process of the invention by reacting 4-chloro-4-chloromethyloxetan-2-one of the formula
HV/HMO / H
Cl >0 H2CC1 (Τ' 10 med dihydrogensulfid i nærværelse af ammoniak, guanidin eller en amin til thiotetronsyre.Cl> 0 H2CC1 (Τ '10 with dihydrogen sulfide in the presence of ammonia, guanidine or an amine for thiotetronic acid.
4-Chlor-4-chlormethyloxetan-2-on kan fremstilles på enkel måde ifølge fremgangsmåden anført i beskrivelsen til europæisk patentansøgning nr. 60.808 og kan efter en 15 flash-destillation anvendes ved fremgangsmåden ifølge opfindelsen.4-Chloro-4-chloromethyloxetan-2-one can be prepared in a simple manner according to the process described in European Patent Application No. 60,808 and can be used in the process of the invention after a flash distillation.
Dihydrogensulfidet anvendes hensigtsmæssigt på gasform.The dihydrogen sulfide is suitably used in gaseous form.
Som egnede aminer anvendes fordelagtige primære, sekundære eller tertiære aminer. Det er særligt fordelagtigt at 20 anvende tertiære aminer, f.eks. triethylamin.As suitable amines, advantageous primary, secondary or tertiary amines are used. It is particularly advantageous to use tertiary amines, e.g. triethylamine.
Det er hensigtsmæssigt at gennemføre omsætningen i et opløsningsmiddel. Som opløsningsmidler anvendes sådanne, som er indifferente over for det reaktive udgangsmateriale, såsom halogenerede carbonhydrider, ethere eller 25 carboxylsyreestere. Som eksempler på anvendelige opløsningsmidler kan nævnes methylenchlorid, chloroform, etheropløsningsmidler, såsom tetrahydrofuran, ellerIt is convenient to carry out the reaction in a solvent. As solvents are used which are inert to the reactive starting material such as halogenated hydrocarbons, ethers or carboxylic esters. Examples of useful solvents include methylene chloride, chloroform, ether solvents such as tetrahydrofuran, or
DK 162766 BDK 162766 B
3 ethylacetat. Det foretrækkes imidlertid især at anvende tetrahydrofuran.3 ethyl acetate. However, it is particularly preferred to use tetrahydrofuran.
Udgangsmaterialerne anvendes hensigtsmæssigt i et 5 molforhold mellem 4-chlor-4-chlormethyloxetan-2-on og dihydrogensulfid samt amin eller guanidin eller ammoniak på fra 1:2:2 til 1:4:3, fortrinsvis fra 1:2,5:2 til 1:3,5:2,5.The starting materials are suitably used in a 5 molar ratio of 4-chloro-4-chloromethyloxetan-2-one to dihydrogen sulfide as well as amine or guanidine or ammonia of from 1: 2: 2 to 1: 4: 3, preferably from 1: 2.5: 2 to 1: 3.5: 2.5.
Der arbejdes fortrinsvis ved temperaturer fra 0eC til 10 -40°C, især fra -10°C til -25°C.Preferably, temperatures are operated from 0 ° C to 10 -40 ° C, especially from -10 ° C to -25 ° C.
Omsætningen gennemføres hensigtsmæssigt på den måde, at opløsningen af udgangsmaterialet mættes med dihydrogensulfid, hvorpå ammoniak, guanidin eller aminen tilsættes over et tidsrum på fra 30-120 minutter.The reaction is conveniently carried out in such a way that the solution of the starting material is saturated with dihydrogen sulfide, to which ammonia, guanidine or the amine is added over a period of from 30-120 minutes.
15 Efter endt amintiIsætning kan oparbejdningen af thio-tetronsyren gennemføres ved frafiltrering af det udfældede salt og derpå følgende inddampning af opløsningen. Remanensen kan til fraskillelse af små mængder dimer anhydrothiotetronsyre optages i etheropløsnings-20 midler, såsom diethylether, tetrahydrofuran eller dioxan, hvorpå opløsningen filtreres gennem et absorptionsmiddel, såsom kiselgel. Efter fornyet inddampning kan thiotetron-syren isoleres på krystallinsk form i godt udbytte.After completion of amine initiation, the working up of the thio-tetronic acid can be carried out by filtration of the precipitated salt and subsequent evaporation of the solution. The residue may be taken up in ether solvents, such as diethyl ether, tetrahydrofuran or dioxane, to separate small amounts of dimeric anhydrothiotetronic acid, and the solution is filtered through an absorbent such as silica gel. After renewed evaporation, the thiotetric acid can be isolated in crystalline form in good yield.
Ved omkrystallisation i aromatiske carbonhydrider, for-25 trinsvis i toluen, kan thiotetronsyren renses yderligere.By recrystallization in aromatic hydrocarbons, preferably in toluene, the thiotetronic acid can be further purified.
Fremgangsmåden ifølge opfindelsen illustreres nærmere i det efterfølgende eksempel.The method according to the invention is further illustrated in the following example.
Eksempel 15,5 g (0,091 mol) 4-chlor-4-chlormethyloxetan-2-on i 300 30 ml tetrahydrofuran afkøles til -20eC, hvorpå opløsningenExample 15.5 g (0.091 mol) of 4-chloro-4-chloromethyloxetan-2-one in 300 ml of tetrahydrofuran is cooled to -20 ° C and the solution
DK 162766 BDK 162766 B
4 mættes med gasformigt dihydrogensulfid. Derefter tilsættes dråbevis ved -15°C i løbet at 1 time en opløsning af 20,2 g (0,2 mol) triethylamin i 100 ml tetrahydrofuran.4 is saturated with gaseous dihydrogen sulfide. Then a solution of 20.2 g (0.2 mole) of triethylamine in 100 ml of tetrahydrofuran is added dropwise at -15 ° C.
5 Reaktionsopløsningen henstår til opvarmning til stuetemperatur, hvorefter det udfældede salt frafiltreres, og opløsningsmidlet fjernes på en rotationsfordamper. Remanensen filtreres gennem en søjle fyldt med kiselgel.The reaction solution is allowed to warm to room temperature, after which the precipitated salt is filtered off and the solvent removed on a rotary evaporator. The residue is filtered through a column filled with silica gel.
Som elueringsmiddel anvendes 300 ml ether. Man får 9,0 g 10 gulfarvet, krystallinsk produkt med smp. 115-117*0. Renheden andrager 89,3% (HPLC). Dette svarer til 8,0 g 100%'s produkt = 75,7%’s udbytte. 7,5 g af den rå thio-tetronsyre omkrystalliseres varmt fra 350 ml toluen. Man får 6,6 g svagt rosafarvet, mikrokrystallinsk produkt med 15 et smeltepunkt på 120°C og en renhed på 96% (HPLC). Dette svarer til 6,3 g 100%'s produkt svarende til et udbytte på 94% eller 71,2%, beregnet på anvendt oxetanon.300 ml of ether is used as the eluent. 9.0 g of 10 yellow colored crystalline product is obtained. 115-117 * 0th Purity is 89.3% (HPLC). This corresponds to 8.0 g of 100% product = 75.7% yield. 7.5 g of the crude thio-tetronic acid is hot recrystallized from 350 ml of toluene. 6.6 g of pale pink microcrystalline product are obtained, having a melting point of 120 ° C and a purity of 96% (HPLC). This corresponds to 6.3 g of 100% product, corresponding to a yield of 94% or 71.2%, based on oxetanone used.
Claims (6)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH192/85A CH663206A5 (en) | 1985-01-16 | 1985-01-16 | METHOD FOR PRODUCING THIOTETRONIC ACID. |
| CH19285 | 1985-01-16 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK17886D0 DK17886D0 (en) | 1986-01-15 |
| DK17886A DK17886A (en) | 1986-07-17 |
| DK162766B true DK162766B (en) | 1991-12-09 |
| DK162766C DK162766C (en) | 1992-04-27 |
Family
ID=4181346
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK017886A DK162766C (en) | 1985-01-16 | 1986-01-15 | PROCEDURE FOR THE PREPARATION OF THIOTETRONIC ACID |
| DK056391A DK162642C (en) | 1985-01-16 | 1991-03-27 | PROCEDURE FOR THE PREPARATION OF THIOTETRONIC ACID |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK056391A DK162642C (en) | 1985-01-16 | 1991-03-27 | PROCEDURE FOR THE PREPARATION OF THIOTETRONIC ACID |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0189096B1 (en) |
| JP (1) | JPS6236375A (en) |
| AT (1) | ATE41929T1 (en) |
| CA (2) | CA1264472A (en) |
| CH (1) | CH663206A5 (en) |
| DE (1) | DE3662688D1 (en) |
| DK (2) | DK162766C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH667655A5 (en) * | 1986-09-24 | 1988-10-31 | Lonza Ag | METHOD FOR PRODUCING 4-ALKOXY-2 (5H) THIOPHENONES. |
| DE10119423A1 (en) | 2001-04-20 | 2002-10-24 | Bayer Ag | New cyanoimino- or nitroimino-substituted azole derivatives or analogs, useful as pesticides, e.g. insecticides, acaricides, nematocides, ectoparasiticides or antifouling agents |
-
1985
- 1985-01-16 CH CH192/85A patent/CH663206A5/en not_active IP Right Cessation
-
1986
- 1986-01-09 JP JP61002839A patent/JPS6236375A/en active Pending
- 1986-01-14 AT AT86100424T patent/ATE41929T1/en not_active IP Right Cessation
- 1986-01-14 EP EP86100424A patent/EP0189096B1/en not_active Expired
- 1986-01-14 DE DE8686100424T patent/DE3662688D1/en not_active Expired
- 1986-01-15 CA CA000499621A patent/CA1264472A/en not_active Expired - Fee Related
- 1986-01-15 DK DK017886A patent/DK162766C/en not_active IP Right Cessation
-
1989
- 1989-06-13 CA CA000602707A patent/CA1267905A/en not_active Expired - Fee Related
-
1991
- 1991-03-27 DK DK056391A patent/DK162642C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DK162642C (en) | 1992-04-13 |
| EP0189096B1 (en) | 1989-04-05 |
| CH663206A5 (en) | 1987-11-30 |
| CA1264472A (en) | 1990-01-16 |
| DK162642B (en) | 1991-11-25 |
| JPS6236375A (en) | 1987-02-17 |
| DE3662688D1 (en) | 1989-05-11 |
| DK17886A (en) | 1986-07-17 |
| DK56391D0 (en) | 1991-03-27 |
| DK56391A (en) | 1991-03-27 |
| CA1267905A (en) | 1990-04-17 |
| DK17886D0 (en) | 1986-01-15 |
| ATE41929T1 (en) | 1989-04-15 |
| DK162766C (en) | 1992-04-27 |
| EP0189096A1 (en) | 1986-07-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2332037T3 (en) | PROCEDURE FOR THE PRODUCTION OF 1,1,1-TRIFLUORO-3-BUTEN-2-ONA SUBSTITUTED. | |
| DK159680B (en) | CYCLIC IMIDES USED FOR THE PREPARATION OF CYCLIC AMINO ACIDS | |
| EP3386945A1 (en) | Solid forms of (2r,4s)-5-(biphenyl-4-yl)-4-[(3-carboxypropionyl)amino]-2- -methylpentanoic acid ethyl ester, its salts and a preparation method | |
| NO151876B (en) | PROCEDURE AND APPARATUS FOR ANIMAL LINING | |
| SU508199A3 (en) | Method for producing morpholine derivatives | |
| NO309718B1 (en) | Process for the preparation of intermediates in the synthesis of benzopyran compounds and intermediates in this process | |
| WO2018125820A1 (en) | Processes for the preparation of pesticidal compounds | |
| NO752493L (en) | ||
| DK160498B (en) | METHOD OF ANALOGUE FOR THE PREPARATION OF 3-METHYL-FLAVON-8-CARBOXYLIC ACID ESTERS OR PHARMACEUTICAL ACCEPTABLE ACID ADDITION SALTS. | |
| DK162766B (en) | PROCEDURE FOR THE PREPARATION OF THIOTETRONIC ACID | |
| DK162095B (en) | PROCEDURE FOR THE PREPARATION OF THIOTETRONIC ACID | |
| NO166712B (en) | PROCEDURE FOR THE PREPARATION OF PYRROLIDO DERIVATIVES. | |
| Shimadzu et al. | Studies on furan derivatives. XIV. Nucleophilic substitution of methyl 5‐nitro‐2‐furancarboxylate and 5‐Nitrofuran‐2‐nitrile | |
| FI88292B (en) | FRAME STARTING FOR N- (SULPHONYLMETHYL) FORMAMIDER | |
| HUT67756A (en) | Process for preparing 5,7-diaryloxy-2-(heteroaryl)triazolo-[1,5a][1,3,5]triazines | |
| Gataullin et al. | Iodocyclization of N-(2-nitrophenyl)-and N-phenyl-N’-[2-(alk-1-enyl) phenyl] ethanimidamides | |
| DK156574B (en) | PROCEDURE FOR PREPARING A RACEMIC OR OPTICALLY ACTIVE 15-HYDROXYIMINO-E-HOMOEBURNAND DERIVATIVE OR ACID ADDITION SALTS THEREOF | |
| PT94205B (en) | PROCESS FOR THE PREPARATION OF 4,5,6,11-TETRAHYDROBENZO {6,7} CYCLOO-OCTA- {1,2-B} THIOFEN-6,11-IMINES AND 6,11-DIHYDROBENZO {6, 7 CYCLO-OCTA- {1,2-B} -THIOFEN-6,11-IMINS | |
| Demirayak et al. | A facile synthesis of some thieno/furo‐[2, 3‐d] pyrimidine‐2‐yl‐thioacetic acid derivatives | |
| CA1293263C (en) | Process for the preparation of substituted sulfonamidobenzamides and a novel intermediate thereto | |
| JP2671401B2 (en) | .ALPHA.-Aminothioacetamide derivative and its production method | |
| KR930006289B1 (en) | Process for preparing dihydrofuranone derivatives | |
| DK162767B (en) | METHOD FOR PREPARING 4-ALKOXY-2 (5H) THIOPHENONES | |
| EP1447397A1 (en) | Polyfunctional sulfonamides and sulfonates and process for preparing them | |
| KR950006149B1 (en) | Novel n-(2-haloalkanoyloxy)succinimide derivative and manufacturing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AHS | Application shelved for other reasons than non-payment | ||
| PBP | Patent lapsed |