DE2700215A1 - Substd. thiophenes prepn. by dehydrogenation - of dihydrothiophenes or disulphido-bis-dihydrothiophenes, using halogen (cpds.) - Google Patents

Abstract

Prepn. of thiophenes of formula involves (i) dehydrogenation of dihydrothiophenes of formula (II) by means of phosphoric acid chloride or bromide SO2Cl2, SO2Br2, Cl2, Br2, I2, or R10 -CO-N(X)-R9 or (ii) dehydrogenation of disulphido-(3,3')-bis-(dihydrothiophenes) of formula (III): or of dihydrothiophenes of formula (IV) by means of SO2Cl, SO2Br2 or Cl2. In the formula R1 is a gap. (V):- R3-O-, R3-S-, r3-2N-, R3-SO3-, R3-CO-S- or R3-CO-O-; R2 is -CO-OR3, -CN, -CO-NR32 or -CO-R4; R3 and R4 are (cyclo)aliphatic, araliphatic or aromatic gps, and R3 may also be H; R1 and R2 may also together form a gp. R5 is H; R6 is -N-R8, -O-, or -S-; R7 is a (cyclo)aliphatic araliphatic or aromatic gp., or R5 and R7 may form, with the 2 adjacent C atoms, part of an aromatic residue; R8 is H or an aliphatic gp.; R9 is H or -CO-R10-R10 is an (ar)aliphatic or aromatic gp., or 2 R10 gps. may form together a -CO-R11 or -NX-C(R3)2-CO- gp.; R11 is an alkylene gp.; R12 has the same meaning as R1; R13 has the same meaning as R12 or when R12 is (V), R13 may be a gp.: X is Cl or Br; and n = 0 or 1.

Description

Thiophene compounds and process for the preparation of

Thiophene compounds Addition to patent application F 26 15 885.0 Die The invention relates to new thiophene compounds and a new process for their preparation of thiophene compounds by dehydration of dihydrothiophenes with certain Halogen compounds.

It is known from Helv Chim Acta 57, 2 487 -> 2 492 (1974) that ethyl 4-hydroxy-5-phenyl-5-dihydrothiophenearboxylate is dehydrated with a large excess of hydrogen peroxide at a higher temperature It is also known that dihydrothiophenes can be dehydrated with tetrachloroquinone (US Pat. No. 3,445,475).

1,4-Dihydro-4-methyl-thieno- [3,4-b] -quinolin-9-3H-one can be used with chloranil becoming dehydrated; the yield of end peat is approx. 30 ffi (monthly bulletins of Chemie 105, 1164-1169 (1974)).

Also from the monthly magazine of chemistry, volume 106, pages 375 to 379 (1975) known that 1,3,4,9-tetrahydrothieno- [3,4-b] 4- "1C ', 5-benzo-diazepin-10-one with chloranil for 18 hours at 60 ° C. to give 4,9-dihydro-thieno-L5,4-b3 [1,5] -benzodiazepin-10-one implements. The work-up is cumbersome and you only get a yield of approx. 20%. As described in the thesis, variations in the response time result in the reaction temperature and the flavoring agent no reaction or only preparative non-usable reaction mixtures.

It is known from German Offenlegungsschrift 1 945 964 that 3-acetylamino-4,5-dihydrothiophene-2-ketones with tetrachloroquinone, nitrosobenzene and iodosobenzene and can preferably dehydrate with selenium and sulfur The starting materials are made by reacting a-haloketones with ß-mercaptonitriles in the presence basic condensing agent and subsequent cyclization of the thioethers formed Sulfur is particularly highlighted as a dehydrating agent and used in used in most of the examples As the German Auslegeschrift 1 643 325 shows, kanr, 3-diethylaminoacetylamino-2-carbomethoxy4> methyl-4,5-dihydrothiophene with Chloranil or bromine can be dehydrated. The yield of 54% of theory is unsatisfactory The German Offenlqgngsschrift 2,537,070 describes the conversion of 5-hydroxy-2-methoxycarbonylthiophene with phosphorus pentachloride in carbon tetrachloride, which leads to 5-chloro-thiophene-2-carboxylic acid leads (example 1).

A reaction before 3-keto-thiophane-4-carboxylic acid methyl ester with a high excess of phosphorus pentachloride for 17 hours also leads to this Replacement of the keto group by a chlorine atom and to 4-chloro-thiophene-3-carboxylic acid chloride (Example 5).

One subject of the main application P 26 15 88500 is a process for the preparation of thiophene compounds of the formula wherein R1 is the radical R3-0-, the radical R3-S-, the radical the rest the rest or the rest means R2 does the rest the rest -CN, the rest the rest denotes, the individual radicals R5 and R4 can be identical or different and each stand for an aliphatic, cycloaliphatic, araliphatic or aromatic radical, in addition R3 can also mean a hydrogen atom, R1 and R2 also together the radical R5 stands for a hydrogen atom, the individual radicals R6 can be identical or different and each represents the radical mean the radical -0-, the radical -S-, the individual radicals R7 can be identical or different and each denote an aliphatic, cycloaliphatic, araliphatic or aromatic radical, the radicals R7 also together with the radicals R5 and the two carbon atoms adjacent to them can represent members of an aromatic radical, R8 represents a hydrogen atom or an aliphatic radical, and n represents 0 or 1, by dehydrogenation of hydrogenated thiophenes with dehydrogenating agents, dihydrothiophenes of the formula in which R1, R2 and R3 have the aforementioned meaning, dehydrogenated with chlorides or bromides of sulfuric acid or with chlorine.

It has now been found that the process of the main application extends further to a process for the preparation of thiophene compounds of the formula wherein R1O has the meaning of R1 or the remainder denotes, and R1, R2 and R3 have the abovementioned meanings, can be configured if the starting materials are dihydrothiophenes of the formula wherein R9 has the meaning of R10 or, when R10 is the remainder means also the rest can denote, R2 and R3 have the aforementioned meaning is used.

Furthermore, the new thiophene compounds of the formula wherein R1O is the radical R3-S-, the radical the rest the rest means R2 does the rest the rest -CN, the rest the rest denotes, the individual radicals R3 and R4 can be identical or different and each stand for an aliphatic, cycloaliphatic, araliphatic or aromatic radical, in addition, R3 can also mean a hydrogen atom -carbmethoxy-thiophene and sulfuryl chloride are represented by the following formulas: In comparison to the known processes, the process according to the invention surprisingly provides a large number of thiophene compounds in a simpler and more economical way, in some cases with better yield, better space-time yield and purity. Cumbersome cleaning operations are avoided. In connection with the German Offenlegungsschrift No. 2,557,070, it is surprising that the 3-hydroxy and 3-keto groups are not replaced to any significant extent by chlorine.

The starting materials III can be prepared in a known manner, for example from α, β-unsaturated carboxylic acids or their esters, amides or nitriles by reaction with thioglycolic acid esters (JACS 68, 2 229-2 235 (1946) ,monthshefte der Chemie 104, 1 520-1 525 (1975)), by reacting ß-mercaptopropionic acid esters with -haloacetic acid derivatives or their esters or amides or α-haloketones, for example α-chloroacetophenone, according to the procedure described in German Offenlegungsschrift 1,945,964 or by reacting 5-oxo Tetrahydro-thiophenes (Organic Reactions VI, 443-468) with diazoalkanes or by reacting the enolate salts with suitable alkylating or acylating reagents, for example alkyl halides, acid anhydrides -6- or sulfonyl halides, can also be obtained from starting amines III by reacting with suitable compounds mentioned above Amines can be obtained in the presence of a catalyst, for example p-toluenesulfonic acid (US Pat. No. 3,445,473). They can be obtained in this way from a starting material III bearing sulfonate groups by reaction with the desired amine. Thiol derivatives III are obtained by reaction with hydrogen sulphide in an inert solvent, 'the thioketones formed can be alkylated or acylated in a known manner (Ber. 100, 93-100 (1967)) Starting thiol derivatives III are reacted. Furthermore, with regard to the preparation of the starting materials III, reference is made to the publications cited in relation to the prior art. the rest the rest the rest the rest or the rest means R2 does the rest the rest -CN, the rest the rest denotes, the individual radicals R5 and R4 can be the same or different and each represent an alkyl radical with 1 to 7 carbon atoms, a cycloalkyl radical with 5 to 7 carbon atoms, an aralkyl radical with 7 to 12 carbon atoms or a phenyl radical, where R3 is advantageous in many cases Contains at least 2 carbon atoms when R2 denotes the radical -COOH and expediently denotes an alkyl group with 2 to 7 carbon atoms, in addition R3 can also denote a hydrogen atom or when R10 denotes the radical denotes, can also represent an acyl radical, for the purpose of an alkanecarbonyl radical having 2 to 7 carbon atoms, R10 and R2 together also represent the radical can denote, R5 represents a hydrogen atom, the individual radicals R6 can be identical or different and in each case the radical denote the radical -O-, the radical -S-, the individual radicals R7 can be identical or different and each represents an alkyl radical with 1 to 7 carbon atoms, a cycloalkyl radical with 5 to 7 carbon atoms, an aralkyl radical with 7 to 12 carbon atoms or a phenyl radical denote, the radicals R7 together with the radicals R5 and the two adjacent carbon atoms can stand for members of a phenylene radical, R8 denotes a hydrogen atom or an alkyl radical with 1 to 7 carbon atoms and n denotes 0 or 1, R9 has the meaning of R10 or, if R10 does the rest means also the rest can denote. The 5-hydroxy compound III can also be in the form of the tautomeric 5-oxo-2-tetrahydro compound III be used. The aforementioned radicals can also be replaced by groups or atoms which are inert under the reaction conditions, e.g.

Carbalkoxy groups with 2 to 4 carbon atoms, alkyl groups, alkoxy groups each having 1 to 4 carbon atoms, carboxyl groups, nitrile groups, the phenyl radicals Substituting chlorine atoms, be substituted There are, for example, starting materials III into consideration: 2-ethoxycarbonyl-, 2-methoxycarbonyl-, 2-n-butoxycarbonyl-, 2-tert. -Butoxycarbonyl-, 2 sec. -Butoxycarbonyl-, 2-propoxycarbonyl-, 2-isobutoxycarbonyl-, 2-isopropoxycarbonyl, 2-phenoxycarbonyl, 2-benzyloxycarbonyl, 2-cyclohexanoxycarbonyl, 2-nitrile-3-hydroxy-dihydrothiophene; (N-methyl) -, (N-ethyl) -, (N-propyl) -, (N-isopropyl) -, (N-Butyl) -, (N-Isobutyl) -, (N-sec-Butyl) -, (N-tert-Butyl) -, (N-Phenyl) -, (N-Benzyl) -, (N-cyclohexyl) -2-carbonamido-3-hydroxy-dihydrothiophene; (N, N-dimethyl) -, (N, N-diethyl) -, (N, N-Dipropyl) -, (N, N-Diisopropyl) -, (N, N-Dibutyl-, (N, N-Di-sec.Butyl) -, (N, N-Di-tert.- butyl) -, (N, N-diisobtyl) -, (N, N-diphenyl) -, (N, N-dibenzyl) -, (N, N-dicyclohexyl) -2-carbonamido-3-hydroxy-dihydrothiophene; 2-methylcarbonyl, 2-ethylcarbonyl, 2-propylcarbonyl, 2-butylcarbonyl, 2-isopropylcarbonyl, 2-cyclohexanylcarbonyl-, 2-benzylcarbonyl-, 2-phenylacetyl-, 2-carbonamido, 2-carboxy-5-hydroxydihydro-thiophene; analogous 3-methoxy, 3-ethoxy, 3-propoxy, 3-isopropoxy, 3-butoxy, 3-isobutoxy, 3-tert-butoxy-, 5-sec. -Butoxy-, 3-phenoxy-, 5-benzoxy-, 3-cyclohexoxy-, 5-methylthio-, 3-ethylthio, 3-propylthio, 3-isopropylthio, 3-butylthio, 3-isobutylthio, 3-sec-butylthio, 3-tert-butylthio, 3-phenylthio, 3-benzylthio, 3-cyclohexylthio compounds; analogous 3-aminothiophenes and on the nitrogen atom once or twice by the methyl, Ethyl, propyl, isopropyl, butyl, isobutyl, secO-butyl, tert-butyl, phenyl, Benzyl, cyclohexyl group-substituted 5-amino compounds; analogous 3-methyl-, 3-ethyl, 3-propyl, 3-isopropyl, 3-butyl, 3-isobutyl, 3-sec-butyl, 3-tert-butyl, 3-cyclohexyl-, 3-phenyl-, 3-benzyl-sulfatothiophenes, 3-methyl-, 3-ethyl-, 3-propyl-, 3-isopropyl, 3-butyl, 3-isobutyl, 3-sec-butyl, 3-tert-butyl, 3-phenyl, 3-benzyl, 3-cyclohexyl-carbonylthio and corresponding 3-carbonyloxy compounds; Dehydrothieno- [2,3-b] quinolinone, appropriate N-methyl-, nthyl-quinolinones, thienochromanones, thienothiochromanones; aforementioned Dihydrothiophenes analog by the methyl, ethyl, propyl, isopropyl, butyl, Isobuty3, sec-butyl, tert-butyl, phenyl, benzyl, cyclohexyl groups in the 4-position or 5-position singly or twice substituted in 4-position and 5-position Dihydrothiophenes The starting materials III are used with the dehydrating agents according to the invention In a stoichiometric amount or in excess, preferably 1 to 2, in particular 1 to 1.1 equivalents of dehydrating agent, based on 1 mole of starting material III, implemented. Sulfuryl chloride, sulfuryl bromide and chlorine are used as dehydrating agents into consideration.

The reaction is usually carried out at a temperature between -30 to + 100 ° C, preferably between +10 to + 40 ° C, under reduced or increased pressure or preferably carried out without pressure, continuously or discontinuously, expediently one uses inert organic solvents such as under the reaction conditions aromatic hydrocarbons, e.g. Toluene, ethylbenzene, o-, m-, p-xylene, isopropylbenzene, Methylnaphthalene, halogenated hydrocarbons, especially chlorinated hydrocarbons, e.g. tetrachlorethylene, 1,1,2,2- or 1,1,1,2-tetrachloroethane, amyl chloride, cyclohexyl chloride, Dichloropropane, methylene chloride, dichlorobutane, isopropyl bromide, n-propyl bromide, butyl bromide, Chloroform, ethyl iodide, propyl iodide, chloronaphthalene, dichloronaphthalene, carbon tetrachloride, Tetrachloroethane, 1,1,1- or 1,1,2-trichloroethane, trichlorethylene, pentachloroethane, cis-dichloroethylene, o-, m-, p-difluorobenzene, 1,2-dichloroethane, l, l-dichloroethane, n-propyl chloride, 1,2-cis-dichloroethylene, n-butyl chloride, 2-, 3-butyl chloride, chlorobenzene ' Fluorobenzene, bromobenzene, iodobenzene, o-, p- and m-dichlorobenzene, o-, p-, m-dibromobenzene, o-, m-, p-chlorotoluene, 1,2,4-trichlorobenzene, l, lO-dibromodecane, 1,4-dibromobutane; Ether, e.g. Ethyl propyl ether, methyl tert-butyl ether, n-butyl ethyl ether, di-n-butyl ether, Diisobutyl ether, diisoamyl ether, diisopropyl ether, anisole, phenetol, cyclohexyl methyl ether, Diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, Thioanisoi, ß, ß'-dichlorodiethyl ether; aliphatic or cycloaliphatic hydrocarbons, e.g. heptane, pinane nonane, gasoline fractions within the boiling point range of 70 to 190 ° C, cyclohexane, methylcyclohexane, petroleum ether decalin, pentane, hexane, Ligroin, 2,2,4-trimethylpentane, 2,2,3-trimethylpentane, 2,3,3-trimethylpentane, octane; Dimethylformamide; and corresponding mixtures.

The solvent is expediently used in an amount of 400 to 10,000 percent by weight, preferably from 400 to 2,000 percent by weight on starting material III. It is also sometimes advantageous to carry out the reaction with light to be carried out with a light source of 2,000 to 8,000 R. Aids can also be used such as azobisisooutyronitrile, expediently from 1 to 5 percent by weight, based on the starting material III, can be added.

It is advantageous to use in the presence of an acid-binding agent stoichiometric amount or in excess, expediently in an amount of 1.9 to 2.1 equivalents of acid-binding agent, based on 1 mole of starting material III. Preferred acid-binding agents are tertiary amines, alkaline earth, ammonium and especially Alkali compounds and corresponding mixtures.

Advantageous alkali and alkaline earth compounds are the hydroxides, Oxides, carbonates, bicarbonates, salts of weak or polybasic acids, alcoholates of calcium, barium, magnesium, lithium and especially sodium and potassium. It are e.g. possible as basic compounds: potassium hydroxide, sodium hydroxide, Potassium carbonate, sodium carbonate, potassium bicarbonate, calcium hydroxide, barium oxide, Magnesium hydroxide, calcium carbonate, sodium acetate, propionate, ethylene glycolate, methylate, propylate, isopropylate, ethylate, tripropylene glycolate, potassium tert-butylate, Trimethylamine, triethylamine, pyridine, diethylaniline, dimethylaminoethanol, N-ethylpiperidine, N-methylpyrrolidine, dimethylaniline, quinoline, N-methylpyrrolidone. Also can basic ion exchangers can be used for acid binding.

The reaction can be carried out as follows: A mixture of the starting material III, the dehydrating agent and optionally the solvent and / or the acid binding agent is used for 0.5 to 3 hours at the reaction temperature held.

The end product is then converted from the mixture in a conventional manner, e.g.

by extraction with one of the aforementioned solvents or washing with alkali, e.g. a sodium bicarbonate solution, and distilling the organic Phase isolated.

The thiophene compounds which can be prepared by the process of the invention are valuable starting materials for the production of pharmaceuticals, dyes and pesticides. All end substances are particularly suitable for this use with the aforementioned preferred radicals. Regarding the use, reference is made to the aforementioned Literature and Ullmann's Encyclopedia of Industrial Chemistry, Volume 17, Page 354, referenced.

The parts listed in the following examples are parts by weight. They relate to parts by volume like the kilogram to the liter.

Example 1 a) (preparation of the starting material): 3-methoxycarbonylmethylthiopropionic acid methyl ester 849 parts of methyl thioglycolate and 8 parts of piperidine are placed in a stirred vessel and cooled to 10 to 15 ° C. 758 parts of methyl acrylate at between 40 and 50 ° C. are added over the course of 2 hours. In the course of the reaction, 4 parts of piperidine each time are added twice. When the addition is complete, the reaction mixture is heated to 60 ° C. for a further 10 minutes and then distilled in a water-jet vacuum. 1,461 parts (95 ff of theory) of methyl 3-methoxyearbonylmethyl-thiopropionate with a boiling point of 142 to 1440 ° C., 1.9 mbar b) are obtained (preparation of the starting material ): 3-Hydroxy-dihydrothiophene-2-carboxylic acid methyl ester 3-Methoxycarbonylmethyl-thiopropionic acid methyl ester (192 parts) are added over 30 minutes to a solution of 360 parts of a 50 percent strength by weight NaOCH5 / MeOH solution at 5 ° C. and the mixture is stirred at 50 ° C. for one hour. The solution is concentrated to a mixture of 200 parts. Poured hydrochloric acid and 1,000 parts of finely divided ice. The oily layer is separated off and the aqueous phase is extracted three times with 100 parts by volume of methylene chloride each time.

The combined organic phases are each 100 parts by volume 5 percent strength by weight NaHCO5 solution extracted three times, dried with sodium sulfate and evaporated.

The residue is distilled in vacuo. 140 parts are obtained (88 % of theory) 3-hydroxy-dihydrothiophene-2-carboxylic acid methyl ester with a boiling point of 72 to 730C / 0.14 mbar.

c) (reaction): 3-hydroxy-thiophene-2-carboxylic acid methyl ester 80 parts of 3-hydroxy-dihydrothiophene-2-carboxylic acid methyl ester are dissolved in 250 parts by volume of methylene chloride. While passing in nitrogen and at 0 ° to 50 ° C., 67.5 parts of sulfuryl chloride in 100 parts by volume of methylene chloride are added in one hour. The mixture is stirred at 0 to 5 ° C. for 2 hours. At 0 to 50 parts, 50 parts of triethylamine are added and the pH is adjusted to 7.5 with triethylamine.

The mixture is tracked at 0 ° C. for 2 hours. Then the mixture adjusted to pH 5 with 10 percent strength by weight hydrochloric acid. The mixture is separated the organic phase twice with 100 parts by volume of saturated sodium chloride solution each time washed out, dried, concentrated and distilled. 65 parts are obtained (82 ff of theory) 3-hydroxy-thiophene-2-carboxylic acid methyl ester with a boiling point of 68 to 750C / 0.4 mbar and mp 42 to 450C.

Example 2 a) (Preparation of the starting material): 5-Hydroxy-5-methyl-dihydrothiophene-2-carboxylic acid methyl ester 54 parts of sodium methylate are suspended in 250 parts by volume of benzene. 76.3 parts of methyl thioglycolate are added at room temperature. The mixture is heated to reflux, then 72 parts of methyl crotonate are added over 30 minutes and the mixture is refluxed for a further 5 hours. The mixture is poured into 150 parts by volume of ice water, the organic phase is separated off, the water phase is acidified with 66 parts of glacial acetic acid and extracted five times with 100 parts by volume of methylene chloride each time. The combined organic phases are washed once with 100 parts by volume of water and once with 50 parts by volume of 5 percent strength by weight NaHCO5 solution, dried and concentrated. The residue is distilled. 42 parts (4% of theory) of 5-hydroxy-5-methyldihydrothiophene-2-carboxylic acid methyl ester with a boiling point of 72 to 750 ° C./0.4 mbar are obtained.

b) (reaction): 3-hydroxy-5-methylthiophene-2-carboxylic acid methyl ester 17.4 parts of 3-hydroxy-5-methyldihydrothiophene-2-carboxylic acid methyl ester are dissolved in 100 parts by volume of methylene chloride. While passing in nitrogen and at 100 ° C., 14.9 parts of sulfuryl chloride in 20 parts by volume of methylene chloride are added in 50 minutes. The mixture is distilled.

12.9 parts (75 ffi of theory) of methyl 3-hydroxy-5-methylthiophene-2-carboxylate are obtained from bp 67 to 700C / 0.5 mbar.

Example 3 a) (preparation of the starting material): methyl 3- (benzoylmethylthio) propionate 15.5 parts of chloroacetophenone are added to a solution, cooled to OOC, of 12 parts of methyl 3-mercaptopropionate and 15.5 parts by volume of triethylamine in 100 parts by volume of chloroform. The mixture is stirred for 2 hours at OOC, washed with water, the organic phase is separated off, dried and concentrated. 21 parts (90% of theory) of methyl 3- (benzylmethylthio) propionate with a boiling point of 156 to 1600 ° C. / 0.3 to 0.55 mbar are obtained.

b) (Preparation of the starting material):; 5-Hydroxy-2-benzoyldihydrothiophene 23.8 parts of methyl 3- (benzoylmethylthio) propionate are added over 30 minutes to 56 parts of a 30 percent strength by weight NaOCH3 / MeOH solution cooled to OOC, and the mixture is stirred at 0 ° to 100 ° C. for 2 hours .

18.5 parts (90% of theory) of 3-hydroxy-2-benzoyldihydrothiophene are obtained from KP 137 to 1400C / 0.16 to 0.08 mbar.

c) (conversion): 3-hydroxy-2-benzoylthiophene The compound is prepared analogously to Example 1c) from 20.6 parts of 3-hydroxy-2-benzoyldihydrothiophene and 6.75 parts of sulfuryl chloride. 16.7 parts (82% of theory) of 3-hydroxy-2-benzoylthiophene with a boiling point of 127 to 132 / 0.5 mbar and a melting point of 53 to 570 ° C. are obtained.

Example 4 a) (preparation of the starting material): 3-cyanomethylthiopropionic acid methyl ester 12 parts of methyl 3-mercaptopropionate and 15.5 parts by volume of triethylamine are placed in 60 parts by volume of dried methylene chloride; at OOC, a solution of 7.6 parts of chloroacetonitrile in 20 parts by volume of methylene chloride is added over the course of 10 minutes and the mixture is stirred for 1.5 hours.

The end product is separated from the reaction mixture analogously to Example 3a). 11.9 parts (75% of theory) of methyl 3-cyanomethylthiopropionate are obtained from bp 95 to 1010C / 0.14 mbar.

b) (preparation of the starting material): 3-hydroxy-2-cyanodihydrothiophene The compound is prepared analogously to Example 3b) from 1.59 parts of methyl 3-cyanomethylthiopropionate and 3.6 parts of a 30 percent strength by weight NaOCH3 / MeOH solution.

10.1 parts (80% of theory) of crude 3-hydroxy-2-cyanodihydrothiophene are obtained, which is used in the next stage without further purification.

c) (preparation of the starting material): 5-methoxy-2-cyano-dihydrothiophene 12.7 parts of 3-hydroxy-2-cyanodihydrothiophene are dissolved in 100 parts by volume of chloroform and 200 parts by volume of an ethereal diazomethane solution (4 percent by weight) are added at OOC. The solution is stirred for 12 hours at OOC and concentrated in vacuo. The residue is distilled. 10.1 parts (72% of theory) of 3-methoxy-2-cyanodihydrothiophene with a boiling point of 82 to 830 ° C./0.35 mbar are obtained.

d) (conversion): 3-methoxy -2-cyanothiophen 14.1 parts of 5-methoxy-2-cyanodihydrothiophene in 80 parts by volume of chloroform are reacted with 6.75 parts of sulfuryl chloride in 20 parts by volume of chloroform at 0 ° C. for 0.5 hours. The end product is separated from the reaction mixture analogously to Example 1c). 12.6 parts (91% of theory) of 3-methoxy-2-cyanothiophene with a boiling point of 730 ° C./0.16 mbar are obtained.

Example 5 a) (preparation of the starting material): 5-acetoxy-dihydrothiophene-2-carboxylic acid methyl ester To a solution, cooled to 0 ° C., of 16 parts of 3-hydroxythiophene-2-carboxylic acid methyl ester and 15.5 parts by volume of triethylamine in 100 parts by volume of chloroform, 8.6 parts of acetyl chloride are added over the course of 10 minutes. The solution is stirred at OOC for 4 hours. After the reaction, the mixture is poured into 100 parts by volume of ice water, and the organic phase is separated off, dried and concentrated. The residue is distilled. 19.4 parts (96% of theory) of methyl 3-acetoxydrothiophene-2-carboxylate with a boiling point of 82 to 840 ° C./0.08 mbar are obtained.

b) (implementation): 3-acetoxythiophene-2-carboxylic acid methyl ester 20.2 parts of 3-acetoxydihydrothiophene-2-carboxylic acid methyl ester are reacted with 6.75 parts by volume of sulfuryl chloride in 150 parts by volume of CCl4 at 0 ° C. for one hour. The end product is separated from the reaction mixture analogously to Example 1c). 15.8 parts (79% of theory) of methyl 3-acetoxythiophene-2-carboxylate with a boiling point of 84 to 860 ° C./0.04 mbar are obtained.

Example 6 a) (preparation of the starting material): 5-methylsulfatodihydrothiophene-2-carboxylic acid methyl ester 16 parts of 5-hydroxydihydrothiophene-2-carboxylic acid methyl ester and 8.6 parts by volume of methanesulfonic acid chloride are dissolved in 100 parts by volume of pyridine at OOC. The solution is stirred at from 0 to 10 ° C. for 15 hours. After the reaction, the mixture is poured into 150 parts by volume of ice water and extracted three times with 50 parts by volume of methylene chloride.

The combined organic phases are twice with 50 parts by volume 10 percent by weight aqueous citric acid solution and three times with saturated Washed sodium chloride solution. After drying and concentrating the organic phases 18.8 parts (79% of theory) of 5-methylsulfatodihydrothiophene-2-carboxylic acid methyl ester are obtained from m.p. 75 to 770C.

b) (reaction): 3-methylsulfatothiophene-2-carboxylic acid methyl ester 23.8 parts of 5-methylsulfatodihydrothiophene-2-carboxylic acid methyl ester are reacted with 6.75 parts by volume of sulfuryl chloride in 125 parts by volume of chloroform at 0 ° C. for 2 hours. The end product is separated from the reaction mixture analogously to Example 1c). 19.6 parts (83% of theory) of oily methyl 3-methylsulfatothiophene-2-carboxylate are obtained.

Example 7 a) (preparation of the starting material): 5-phenylthiodihydrothiophene-2-carboxylic acid methyl ester 2.38 parts of 5-methylsulfatodihydrothiophene-2-carboxylic acid methyl ester are placed in 10 parts by volume of dimethylformamide and cooled to 0.degree. 1.45 parts of sodium thiophenolate in 10 parts by volume of dimethylformamide are added over the course of 15 minutes and the mixture is subsequently stirred at OOC for one hour.

The reaction mixture is added in 50 parts by volume of water and extracted three times with 25 parts by volume of methylene chloride each time. The united organic Phase is dried and concentrated. 2.08 parts (88% of theory) of 5-phenylthiodihydrothiophene-2-carboxylic acid methyls are obtained ter from m.p. 43 to 450C.

b) (implementation):) -Phenylthiothiophene-2-carboxylic acid methyl ester Analogously to Example 1c), 2.52 parts of 3-phenylthiodihydrothiophene-2-carboxylic acid methyl ester are obtained by reaction for 2 hours at OOC with 0.66 parts of sulfuryl chloride (2.33 parts) 3-phenylthiophene-2-carboxylic acid methyl ester (93% of theory) from m.p. 63 to 660C.

Example 8 a) (preparation of the starting material): 3-amino-2-benzoyldihydrothiophene 8.7 parts of β-mercaptopropionitrile are added to a solution of 2.6 parts of sodium in 175 parts by volume of methanol at 220 ° C. with stirring. After 10 minutes, a 550C solution of 15.5 parts of chloroacetophenone is added in 50 minutes and the temperature is maintained at 220C. The mixture is allowed to stir for 50 minutes at 220 ° C. and then heated under reflux to 65 ° C. for 2 hours. The cooled reaction mixture is neutralized with acetic acid, poured into 250 parts of ice water and extracted three times with 50 parts by volume of chloroform each time. After the combined, dried chloroform extracts have been evaporated, an oily residue remains which is triturated with 50 parts of cold alcohol and crystallizes in the process. 17.5 parts (85% of theory) of 3-amino-2-benzoyl-dihydrothiophene with a melting point of 147 ° to 1490 ° C. are obtained.

b) (conversion): 3-amino-2-benzoylthiophene Analogously to Example 1c), 1.6 parts (77% of theory) of 3-amino-2-benzoylthiophene are obtained from 2.05 parts of 3-amino-2-benzoyl-dihydrothiophene by reacting at OOC with 0.66 parts of sulfuryl chloride for one hour from m.p. 100 to 1020 C.

Example 9 a) (preparation of the starting material): 3-acetylamino-2-benzoyldihydrothiophene 2.05 parts of 5-amino-2-benzoyl-dihydrothiophene are heated in 10 parts by volume of acetic anhydride at 80 ° C. for 2 hours. After removal of the acetic anhydride and recrystallization of the residue from ethanol, 2.5 parts (95% of theory) of 3-acetylamino-2-benzoyl-dihydrothiophene with a melting point of 65 ° to 660 ° C. are obtained.

b) (conversion): 3-acetylamino-2-benzoylthiophene Analogously to Example 1c), 2.47 parts of 3-acetylamino-2-benzoyldihydrothiophene are obtained by reacting for one hour at OOC with 0.66 parts of sulfuryl chloride (2.0 parts) of 3-acetylamino-2-benzoylthiophene (82% of theory) with melting point 93 to 950C.

Example 10 a) (preparation of the starting material): disulfido (5,5 ') bis (dihydrothiophene-2-carboxylic acid methyl ester) 50 parts by volume of dimethylformamide and 9.52 parts of 3-methylsulfatodihydrothiophene-2-carboxylic acid methyl ester are initially introduced. 5.5 parts of disodium disulfide 5H20 are added at 20 to 25 ° C. in portions over the course of one hour. The mixture is stirred at OOC for 6 hours, diluted with 200 parts by volume of methylene chloride and poured into 200 parts of ice water. The organic phase is separated off, washed five times with 200 parts by volume of water each time, dried with sodium sulfate, filtered off and concentrated. The residue is recrystallized from toluene. 5.25 parts (75% of theory) of disulfido (3,3 ') bis (dihydrothiophene-2-carboxylic acid methyl ester) of melting point 155 to 1) 7 ° C. are obtained.

b) (conversion): disulfido- (3-3 ') - bis- (thiophene-2-carboxylic acid methyl ester) 50 parts by volume of methylene chloride and 3.5 parts of disulfido (3,3 ') - bis (dthydrothiophene-2-carboxylic acid methyl ester) are presented. At 20 to 25 ° C., 1.62 parts by volume of sulfuryl chloride are added over the course of 15 minutes. The reaction mixture is stirred for 30 minutes at 250 ° C., diluted with 50 parts by volume of methylene chloride, washed three times with 100 parts by volume of water each time, dried with sodium sulfate, filtered off and concentrated. 3.39 parts (98% of theory) of disulfido (3,3 ') bis (thiophene-2-carboxylic acid methyl ester) of melting point 141 to 1450 ° C. are obtained.

Claims (2)

Claims 1. Verrahren for the preparation of thiophene compounds of the formula wherein R1O has the meaning of R1 or the remainder referred to, according to the procedure for the preparation of thiophene compounds of the formula wherein R1 is the radical R3-o-, the radical R3-S-, the radical the rest the rest or the rest means R2 does the rest the rest -CN, the rest the rest denotes, the individual radicals R3 and R4 can be identical or different and each stand for an aliphatic, cycloaliphatic, araliphatic or aromatic radical, in addition R3 can also mean a hydrogen atom, R1 and R2 also together the radical can denote, R 'stands for a hydrogen atom, the individual radicals R can be identical or different and in each case the radical mean the radical -O-, the radical -S-, the individual radicals R7 can be identical or different and each denote an aliphatic, cycloaliphatic, araliphatic or aromatic radical, the radicals R7 also together with the radicals 5 and the two carbon atoms adjacent to them may represent members of an aromatic radical, R8 denotes a hydrogen atom or an aliphatic radical, and n stands for 0 or 1, by dehydrogenation of hydrogenated thiophenes with dehydrogenating agents, dihydrothiophenes of the formula wherein R1, R2 and R3 have the aforementioned meanings, dehydrated with chlorides or bromides of sulfuric acid or with chlorine, according to patent application P 26 15 88500, characterized in that the starting materials are dihydrothiophenes of the formula wherein R9 has the meaning of R10 or, when R10 is the remainder means also the rest can denote, R2 and R3 have the aforementioned meaning is used. 2. Thiophene compounds of the formula wherein R10 is the radical R³-S-, the radical the rest the rest means R2 does the rest the rest -CN, the rest the rest denotes, the individual radicals R³ and R4 can be identical or different and each stand for an aliphatic, cycloaliphatic, araliphatic or aromatic radical, in addition R3 can also mean a hydrogen atom.