DE3330604A1 - Process for the preparation of bromomethylthiophenecarboxylic acid esters - Google Patents
Process for the preparation of bromomethylthiophenecarboxylic acid estersInfo
- Publication number
- DE3330604A1 DE3330604A1 DE19833330604 DE3330604A DE3330604A1 DE 3330604 A1 DE3330604 A1 DE 3330604A1 DE 19833330604 DE19833330604 DE 19833330604 DE 3330604 A DE3330604 A DE 3330604A DE 3330604 A1 DE3330604 A1 DE 3330604A1
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- water
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- brominated
- formula
- bromine
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- 238000000034 method Methods 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- MBUJPYIAHYOTJE-UHFFFAOYSA-N 3-(bromomethyl)thiophene-2-carboxylic acid Chemical class OC(=O)C=1SC=CC=1CBr MBUJPYIAHYOTJE-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 230000031709 bromination Effects 0.000 description 10
- 238000005893 bromination reaction Methods 0.000 description 10
- 239000012071 phase Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- -1 thiophene radical Chemical class 0.000 description 6
- QENGPZGAWFQWCZ-UHFFFAOYSA-N 3-Methylthiophene Chemical compound CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- AJDIZQLSFPQPEY-UHFFFAOYSA-N 1,1,2-Trichlorotrifluoroethane Chemical compound FC(F)(Cl)C(F)(Cl)Cl AJDIZQLSFPQPEY-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000002148 esters Chemical group 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- OCMXPYWVGOAQCG-UHFFFAOYSA-N methyl 3-(dibromomethyl)thiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1C(Br)Br OCMXPYWVGOAQCG-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229930192474 thiophene Natural products 0.000 description 3
- 150000003577 thiophenes Chemical class 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- UZTZDXILWKKQRB-UHFFFAOYSA-N ethyl 3-methylthiophene-2-carboxylate Chemical class CCOC(=O)C=1SC=CC=1C UZTZDXILWKKQRB-UHFFFAOYSA-N 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- INQCGTXAYKWHGH-UHFFFAOYSA-N methyl 3-(bromomethyl)thiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1CBr INQCGTXAYKWHGH-UHFFFAOYSA-N 0.000 description 2
- BRWROFVPMUPMJQ-UHFFFAOYSA-N methyl 3-methylthiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1C BRWROFVPMUPMJQ-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- UFVAMULWEWSKFU-UHFFFAOYSA-N 2-(1-benzoxepin-8-yl)acetic acid Chemical class C1=CC=COC2=CC(CC(=O)O)=CC=C21 UFVAMULWEWSKFU-UHFFFAOYSA-N 0.000 description 1
- QZOBOLDDGXPTBP-UHFFFAOYSA-N 2-(bromomethyl)thiophene Chemical compound BrCC1=CC=CS1 QZOBOLDDGXPTBP-UHFFFAOYSA-N 0.000 description 1
- XQQBUAPQHNYYRS-UHFFFAOYSA-N 2-methylthiophene Chemical compound CC1=CC=CS1 XQQBUAPQHNYYRS-UHFFFAOYSA-N 0.000 description 1
- KBWHYRUAHXHHFO-UHFFFAOYSA-N 3-(bromomethyl)thiophene Chemical compound BrCC=1C=CSC=1 KBWHYRUAHXHHFO-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- IFLKEBSJTZGCJG-UHFFFAOYSA-N 3-methylthiophene-2-carboxylic acid Chemical class CC=1C=CSC=1C(O)=O IFLKEBSJTZGCJG-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Verfahren zur Herstellung von Brommethylthiophen-Process for the production of bromomethylthiophene
Carbonsäureestern In der DAS 2637110 (HOE 75 F 279) werden Benzoxepin-8-essigsäuren und deren Alkylester der allgemeinen Formel beschrieben, in der R Wasserstoff oder -Alkylrest und A u.a. ein Thiophenrest der Form bedeuten kann. In der EP-OS 0 071 127 (HOE 81 S 016) werden Derivate der allgemeinen Formel beschrieben, in der X wie oben ein Thiophenrest, R2 ein Wasserstoffatom oder ein C1 5-Alkylrest und R3 eine Hydroxyl~ gruppe bzw. ein Rest der Form sein kann, wobei R4 ein geradkettiges oder verzweigtes Alkyl ist.Carboxylic acid esters In DAS 2637110 (HOE 75 F 279) benzoxepine-8-acetic acids and their alkyl esters of the general formula described, in which R is hydrogen or -Alkyl radical and A can mean, inter alia, a thiophene radical of the form. In EP-OS 0 071 127 (HOE 81 S 016) derivatives of the general formula in which X, as above, is a thiophene radical, R2 is a hydrogen atom or a C1-5-alkyl radical and R3 is a hydroxyl group or a radical of the form may be, where R4 is a straight-chain or branched alkyl.
Diese Verbindungen besitzen entzündungshemmende und schmerzstil leide Eigenschaften. These compounds have anti-inflammatory and pain relief Properties.
Schlüsselverbindungen zur Herstellung solcher Derivate, ist ein 3-Brommethylthiophen-2-carbonsäureester der allgemeinen Formel in der R ein C1-C5-Alkylrest, geradkettig oder verzweigt, sein kann.The key compound for the production of such derivatives is a 3-bromomethylthiophene-2-carboxylic acid ester of the general formula in which R can be a C1-C5-alkyl radical, straight-chain or branched.
Solche Thiophenderivate, die gleichzeitig eine Esterfunktion besitzen, können durch Bromierung der entsprechenden Methylverbindungen erhalten werden. Such thiophene derivatives, which at the same time have an ester function, can be obtained by bromination of the corresponding methyl compounds.
R.D. Tilak et al., (Tetrahydron [London] 23 (1967), 5, 2443-51), synthetisieren diese Thiophenderivate durch Umsetzung von Methyl-thiophen-carbonsäureäthylestern mit N-Bromsuccinimid in Gegenwart von Benzoylperoxid als Initiator in Tetrachlorkohlenstoff als Lösungsmittel. Die erhaltenen Rohprodukte müssen destillativ gereinigt werden.R.D. Tilak et al., (1967 Tetrahydron [London] 23: 5, 2443-51) these thiophene derivatives by reaction of methyl-thiophene-carboxylic acid ethyl esters with N-bromosuccinimide in the presence of benzoyl peroxide as initiator in carbon tetrachloride as a solvent. The raw products obtained have to be purified by distillation.
Die Ausbeuten liegen je nach Substitutionsmuster des Thiophens zwischen 74-83 % d.Th..The yields are between, depending on the substitution pattern of the thiophene 74-83% of the total.
In einer weiteren Patentanmeldung (FR 2428-639) wird die Bromierung von unter identischen Bedingungen in 71 %iger Ausbeute beschrieben.In another patent application (FR 2428-639) the bromination of described under identical conditions in 71% yield.
Nachteile dieser Verfahren sind der Einsatz eines teuren Bromierungsagens, die Verwendung eines toxischen Lösungsmittels, vor allem die Gefahr meist spontan verlaufender Radikalreaktionen für den technischen Maßstab, sowie eine verminderte Selektivität, so daß eine destillative Reinigung erforderlich ist.Disadvantages of these processes are the use of an expensive bromination agent, the use of a toxic solvent, especially the danger mostly spontaneous radical reactions taking place on an industrial scale, as well as a reduced one Selectivity, so that purification by distillation is necessary.
Alkylthiophene, ohne Esterfunktion, können in der Seitenkette auch mit elementarem Brom bromiert werden (Synthetic Chem. Ltd., Belg. Pat. 825-833). Bei der Bromierung von 3-Methylthiophen mit Brom unter Belichtung in Tetrachlorkohlenstoff als Lösungsmittel und in Gegenwart von Azoisobutyronitril wird das 3-Brommethylderivat in 67 %einer Ausbeute erhalten. Das erhaltene, rohe Produktgemisch besteht zu il mul7Ó aus 3-Methylthiophen, 60 % aus 3-Brommethylthiophen, 18,5 % aus 3-Dibrommethylen-Thiophen und zu 10,5 mol% aus kernbromierten Produkten.Alkylthiophenes, without an ester function, can also be in the side chain be brominated with elemental bromine (Synthetic Chem. Ltd., Belg. Pat. 825-833). During the bromination of 3-methylthiophene with bromine with exposure to light in carbon tetrachloride as a solvent and in the presence of azoisobutyronitrile is the 3-bromomethyl derivative obtained in 67% yield. The crude product mixture obtained consists of il Mul7Ó from 3-methylthiophene, 60% from 3-bromomethylthiophene, 18.5% from 3-dibromomethylene thiophene and to 10.5 mol% from nuclear brominated products.
Nachteile dieses Verfahrens sind die Anwendung eines toxischen Lösungsmittel(CCl4) sowie die mangelnde Selektivität.Disadvantages of this process are the use of a toxic solvent (CCl4) as well as the lack of selectivity.
Ferner wurde nicht dokumentiert, daß unter diesen Reaktionsbedingungen ohne weitere Nebenreaktionen gleichzeitig auch eine Esterfunktion im Molekül anwesend sein kann.Furthermore, it has not been documented that under these reaction conditions without further side reactions, an ester function is also present in the molecule at the same time can be.
Die jüngsten Entwicklungen in der pharmazeutischen Ånwendung von Thiophenverbindungen als chemische Intermediate oder als Bausteine in pharmakologisch wirksamen Verbindungen indizieren, daß ein Verfahren benötigt wird, solche Intermediate ohne Umweltprobleme, zu vernünftigen Kosten, sicher und ohne größere Nebenproduktbildung herzustellen.Recent Developments in the Pharmaceutical Use of Thiophene Compounds as chemical intermediates or as building blocks in pharmacologically active compounds indicate that a process is needed to process such intermediates without environmental problems, at a reasonable cost, safely, and without major by-product formation.
Das von uns entwickelte Verfahren wird diesem Anspruch gerecht, indem es - die gelinde verlaufendere lichtkatalysierte Bromierung mit Brom verwendet - als Bromierungsagens anstelle von N-Bromsuccinimid das billigere Brom einsetzt - anstelle des toxischen Tetrachlorkohlenstoffs ein Zweiphasensystem aus Wasser und einem mit Wasser nicht mischbaren Fluor-Chloralkan, 1 1 2-Trichlor-1 1 2-trifluorethan als Lösungsmittel verwendet - durch Arbeiten im Zweiphasensystem mit Wasser unter Bindung der freiwerdenden Bromwasserstoffsäure Abluftprobleme mindert bzw. vermeidet.The process we have developed meets this requirement by it - the milder light-catalyzed bromination with Bromine used - as a brominating agent instead of N-bromosuccinimide, the cheaper one Bromine uses a two-phase system instead of the toxic carbon tetrachloride from water and a water-immiscible fluoro-chloroalkane, 1 1 2-trichloro-1 1 2-trifluoroethane used as a solvent - by working in the two-phase system with water while binding the released hydrobromic acid reduces exhaust air problems or avoids.
Das bei gelinden Temperaturen durchgeführte Verfahren bietet auch den Vorteil, daß die gewünschten Verbindungen in hoher Selektivität erhalten werden und somit auf eine weitere Reinigung durch eine gezielte Reaktionsführung verzichtet werden kann.The procedure performed at mild temperatures also offers the advantage that the desired compounds are obtained with high selectivity and therefore no further purification by means of a targeted reaction process can be.
Zur Herstellung der Verbindungen (II) aus (I) in denen R ein Alkylrest mit 1 bis 5-Kohlenstoffatomen bedeuten kann, werden die Methyl-thiophen-carbonsäureester in einem Fluorchloralkan gelöst, mit Wasser unterschichtet und bei mäßigen Temperaturen eine Lösung von Brom in diesem Fluorchloralkan unter gleichzeitiger Belichtung zudosiert. Nach beendeter Bromzugabe wird die wässrige Phase abgetrennt, die verbleibende organische Phase konzentriert und abgekühlt. Das gewünschte Produkt kristallisiert aus.For the preparation of the compounds (II) from (I) in which R can be an alkyl radical with 1 to 5 carbon atoms, the methyl-thiophene-carboxylic acid esters are dissolved in a fluorochloroalkane, underlaid with water and, at moderate temperatures, a solution of bromine in this fluorochloroalkane is added with simultaneous exposure to light. When the addition of bromine is complete, the aqueous phase is separated off, and the remaining organic phase is concentrated and cooled. The desired product crystallizes out.
Unter mäßigen Temperaturen sind solche zwischen Rauntemperatur und ca. 100°C zu verstehen. Das Verhältnis von Methylthiophen zu Brom kann 1:0,8 bis 1:2 mol betragen, vorzugsweise werden äquimolare Mengen oder bis zu 10% Ueberschuß an Brom verwendet. Die Bromierung kann bis zur Rückflußtemperatur des Lösungsmittels durchgeführt werden.Under moderate temperatures are those between room temperature and to understand approx. 100 ° C. The ratio of methylthiophene to bromine can be 1: 0.8 to 1: 2 mol, equimolar amounts or up to 10% excess are preferred used on bromine. The bromination can be carried out up to the reflux temperature of the solvent be performed.
Als Fluorchloralkane kommen z.B. die Verbindungen CCl2FCCl2F und CCl2FCCLF2 infrage. Vorzugsweise wird 1,1,2-Trichlor-1,1,2-trifluorethan frigen 113) verwendet.The compounds CCl2FCCl2F and CCl2FCCLF2, for example, are used as fluorochloroalkanes in question. Preference is given to using 1,1,2-trichloro-1,1,2-trifluoroethane (frigen 113).
Das Volumenverhältnis von Wasser zum Fluorchloralkan ist unproblematisch. Für die Verwendung von SFrigen 113 z.B.The volume ratio of water to fluorochloroalkane is not a problem. For the use of SFrig 113 e.g.
kann es 1:8 bis 1:2, vorzugsweise 1:3,5 betragen. Zur Belichtung kann monochromatisches Licht der Wellenlängen von 320-615 nm verwendet werden. Bevorzugt sind Wellenlängen, die in der Nähe des Absorptionsmaximums des Broms von 420 nm liegen. Die folgenden Ausführungsbeispiele sollen die Erfindung erläutern.it can be 1: 8 to 1: 2, preferably 1: 3.5. For exposure can monochromatic light with a wavelength of 320-615 nm can be used. Preferred are wavelengths that are close to the absorption maximum of bromine of 420 nm lie. The following exemplary embodiments are intended to explain the invention.
Beispiel 1 0,5 Mol (79,59; 98,3 %ig) 3-Methyl-thiophen-2-Carbonsauremethylester werden in einen Reaktionskolben in 1000 ml "Frigen 113't gelöst und mit 200 ml Wasser unterschichtet.Example 1 0.5 mol (79.59; 98.3%) 3-methyl-thiophene-2-carboxylic acid methyl ester are dissolved in 1000 ml of "Frigen 113't" in a reaction flask and mixed with 200 ml of water layered.
Man heizt auf Rückflußtemperatur hoch und läßt unter Rühren und 91eichzeitiger Belichtung (445 nm) eine Lösung von 0,5 Mol Brom (79,9 g; ca. 25 ml) in 75 ml "Frigen-113" während 3 bis 4 Stunden zutropfen. Der Ansatz wird nach beendeter Zugabe 0,5-2,5 Stunden unter Rückfluß nachgerührt und dann auf Raumtemperatur abgekühlt. Die Friqen-Phase wird abgetrennt, mit 200 ml einer Frigen NaOH-Lösung gewaschen und über Natriumsulfat getrocknet.The mixture is heated to the reflux temperature and left with stirring and at the same time Exposure (445 nm) a solution of 0.5 mol of bromine (79.9 g; approx. 25 ml) in 75 ml of "Frigen-113" add dropwise over 3 to 4 hours. When the addition is complete, the batch is 0.5-2.5 Stirred under reflux for hours and then cooled to room temperature. The Friqen phase is separated off, washed with 200 ml of a Frigen NaOH solution and over sodium sulfate dried.
Die GC-Analyse der Frigenphase ergab ca. 75 Mol% an 3-Brommethyl-thiophencarbonsäurelnethylester, ca. 11 ,0 an nicht bromi ertem Ausgangsmateri al.ca. 9 % an Kernbromi erungsprodukten sowie ca. 5 % an 3-Dibrommethyl-thiophen-2-Carbonsäuremethylester.The GC analysis of the Frigen phase showed approx. 75 mol% of 3-bromomethyl-thiophenecarboxylic acid methyl ester, approx. 11.0 of non-brominated starting material approx. 9% in nuclear bromination products and about 5% of 3-dibromomethyl-thiophene-2-carboxylic acid methyl ester.
Die Frigenphase wird im Vakuum auf ca. 250 nil konzentriert und aus -10 °C abgekühlt. Das gewünschte Produkt kristallisiert aus. Man isoliert 87,9 g (74,8 % d.Th.) an 3-Brommethyl thi ophencarbonsäure vom Schmp. 47-52 °C. Die Verbindung ist nach Schmelzpunkt und Mischschmelzpunkt mit der Literatur bekannten Substanz identisch.The free phase is concentrated in vacuo to approx. 250 nil and off -10 ° C cooled. The desired product crystallizes out. 87.9 g are isolated (74.8% of theory) of 3-bromomethyl thiophenecarboxylic acid with a melting point of 47-52 ° C. The connection is substance known from the literature according to its melting point and mixed melting point identical.
Beispiel 2: Wie Beispiel 1, wobei ein Zweiphasensystem Wasser/Frigen von 100/800 ml und 0,65 Mol Brom ad 100 ml Frigen verwendet wurde. Die Bromierung wurde unter Belichtung mit Licht der Wellenlänge 320 nm durchgeführt. Das Rohprodukt, die Frigenphase bestand zu 68 % aus dem 3-Brommethyl-Derivat, zu 10 % aus nicht umgesetztem Startmaterial, zu 12 % aus kernbromierten Produkten sowie zu ca. 10 % aus dem 3-Dibrommethyl-thiophen-2-Carbonsäuremethylester.Example 2: As Example 1, with a two-phase system water / Frigen of 100/800 ml and 0.65 mol of bromine was used ad 100 ml of Frigen. The bromination was carried out with exposure to light of wavelength 320 nm. The raw product, 68% of the free phase consisted of the 3-bromomethyl derivative and 10% of none converted starting material, 12% from core brominated products and approx. 10 % from the 3-dibromomethyl-thiophene-2-carboxylic acid methyl ester.
Die Aufarbeitung erfolgte wie unter Beispiel 1 beschrieben.Work-up was carried out as described in Example 1.
Beispiel 3: Wie Beispiel 1, wobei ein Zweiphasensystem Wasser/Frigen von 300/600 ml verwendet und zur Bromierung bei 320 nm 0,65 Mol Br eingesetzt wurden. Das Rohprodukt enthielt 2 ca. 69 % an 3-Brommethyl-thiophen-2-carbonsäuremethylester, jeweils ca. 11 % an kernbromierten und Dibrom-Derivaten sowie noch 9 % an Ausgangsmaterial. Aufarbeitung wie in Beispiel 1.Example 3: As Example 1, with a two-phase system water / Frigen of 300/600 ml were used and 0.65 mol of Br were used for bromination at 320 nm. The crude product contained 2 approx. 69% of 3-bromomethyl-thiophene-2-carboxylic acid methyl ester, approx. 11% each of nuclear brominated and dibromine derivatives and 9% of starting material. Work-up as in Example 1.
Beispiel 4: Wie Ausführungsbeispiel 1, wobei 0,5 Mol 3-Methyl-thiophen-2-Carbonsäuremethylester in 700 ml "Frigen-113itgelöstÆ mit 200 ml Wasser unterschichtet und mit 0,65 Mol Br2 ad 100 ml "Frigen-113" bromiert wurde. Die GC-Analyse der Frigenphase ergab: 77 % an 3-Brommethyl-, 14 % an 3-Dibrommethylthiophencarbonsäuremethylester. 3 % Ausqanqsmaterial sowie 6 % an kernbromierten Produkten.Example 4 As embodiment 1, with 0.5 mol of 3-methyl-thiophene-2-carboxylic acid methyl ester in 700 ml "Frigen-113itgelöstÆ with 200 ml of water and with 0.65 mol Br2 was brominated to 100 ml "Frigen-113". The GC analysis of the free phase showed: 77% of 3-bromomethyl-, 14% of 3-dibromomethylthiophenecarboxylic acid methyl ester. 3% Ausqanqsmaterial as well as 6% of core brominated products.
Beispiel 5: Wie Beispiel 4, wobei mit Licht der Wellenlänge 615 nm belichtet wurde. Die Analyse des rohen Produktgemisches ergab: 68 % an 3-CH2Br-, 8 % an 3-CHBr2-, 14 % an kernbromierten Derivaten und 10 % an Startmaterial.Example 5: As Example 4, except that light with a wavelength of 615 nm was exposed. Analysis of the crude product mixture showed: 68% of 3-CH2Br-, 8% of 3-CHBr2-, 14% of nuclear brominated derivatives and 10% of starting material.
Beispiel 6: Wie Beipsiel 4, wobei 1 Mol Brom ad 100 ml Frigen verwendet wurden. Das Rohprodukt enthält 63 % an 3-CH2Br, 11 % an 3-CHBr2> 9 % Ausgangsmaterial sowie 17 % an kernbromierten Produkten. Die Bromierung wurde unter Belichtung mit Licht von 320 nm durchgeführt.Example 6: As Example 4, using 1 mol of bromine to 100 ml of Frigen became. The crude product contains 63% 3-CH2Br, 11% 3-CHBr2> 9% starting material as well as 17% of core brominated products. The bromination was with exposure to light Light of 320 nm carried out.
Beispiel 7: Wie Beispiel 6> wobei 0,45 Mol Brom eingesetzt wurden.Example 7: As Example 6> except that 0.45 mol of bromine were used.
Das Rohprodukt setzte sich zusammen aus: 52 % 3-CH2Br, 34 % Ausgangsmaterial, 3 % 3-CHBr2- und 11 % an kernbromierten Derivaten des Startmaterial 5.The crude product was composed of: 52% 3-CH2Br, 34% starting material, 3% 3-CHBr2- and 11% of nuclear brominated derivatives of the starting material 5.
Beispiel 8: Wie Ausführungsbeispiel 1, wobei 0.5 Mnl 3-Methylthiophen-2-Carbonsaureäthylester als Startmaterial eingesetzt wurde.Example 8 As embodiment 1, with 0.5 Mnl 3-methylthiophene-2-carboxylic acid ethyl ester was used as starting material.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19833330604 DE3330604A1 (en) | 1983-08-25 | 1983-08-25 | Process for the preparation of bromomethylthiophenecarboxylic acid esters |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19833330604 DE3330604A1 (en) | 1983-08-25 | 1983-08-25 | Process for the preparation of bromomethylthiophenecarboxylic acid esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3330604A1 true DE3330604A1 (en) | 1985-03-28 |
Family
ID=6207373
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19833330604 Withdrawn DE3330604A1 (en) | 1983-08-25 | 1983-08-25 | Process for the preparation of bromomethylthiophenecarboxylic acid esters |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE3330604A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8563734B2 (en) | 2008-11-13 | 2013-10-22 | Basf Se | 2-[1-cyanopropyl)carbamoyl]-5-chloromethyl nicotinic acids and the use thereof in manufacturing herbicidal imidazolinones |
| US8629279B2 (en) | 2008-12-09 | 2014-01-14 | Basf Se | Process for manufacturing 5-formyl-pyridine-2,3-dicarboxylic acid esters |
| US8722893B2 (en) | 2008-11-13 | 2014-05-13 | Basf Se | Process for manufacturing 5-chloromethyl-2,3-pyridine dicarboxylic acid anhydrides |
| US9096570B2 (en) | 2008-11-13 | 2015-08-04 | Basf Se | Process for manufacturing substituted 3-pyridylmethyl ammonium bromides |
-
1983
- 1983-08-25 DE DE19833330604 patent/DE3330604A1/en not_active Withdrawn
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8563734B2 (en) | 2008-11-13 | 2013-10-22 | Basf Se | 2-[1-cyanopropyl)carbamoyl]-5-chloromethyl nicotinic acids and the use thereof in manufacturing herbicidal imidazolinones |
| US8722893B2 (en) | 2008-11-13 | 2014-05-13 | Basf Se | Process for manufacturing 5-chloromethyl-2,3-pyridine dicarboxylic acid anhydrides |
| US9096570B2 (en) | 2008-11-13 | 2015-08-04 | Basf Se | Process for manufacturing substituted 3-pyridylmethyl ammonium bromides |
| US9278977B2 (en) | 2008-11-13 | 2016-03-08 | Basf Se | Process for manufacturing 5-chloromethyl-2,3-pyridine dicarboxylic acid anhydrides |
| US8629279B2 (en) | 2008-12-09 | 2014-01-14 | Basf Se | Process for manufacturing 5-formyl-pyridine-2,3-dicarboxylic acid esters |
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