DD216237A1 - METHOD FOR PRODUCING SUBSTITUTED 4-PHENYL-THIOPHENES - Google Patents

Abstract

The invention relates to a process for the preparation of substituted 4-phenyl-thiophenes. Here, phenylacetaldehyde is reacted with a heterocumulene, such as carbon disulfide or an isothiocyanate, in an aprotic solvent with addition of a base, and the resulting geminal dithiolate with a halogen-active CH-acidic compound or first with an alkyl halide and then with a halo-active CH Acids -acid compound or the monosodium salt reacted with a halogen-active CH-acidic compound, then the reaction mixture verduennt, isolated the resulting oil and treated with methanolic sodium methylate solution. The thus synthesized thiophenes can be used as intermediates for organic syntheses.

Description

Process for the preparation of substituted 4- phenylthiophenes

Field of application of the invention ,

The invention relates to a process for the preparation of substituted 4-phenylthiophenes of general formula

1 mel I, in which R is an acyl, ester, nitro or nitrile group and Y is an alkylthio group -S-CH ₀ -R,

2 '

in the R, hydrogen, alkyl, aryl or an acyl, ester,

Nitro, nitrile group, or an amino group -NHR ^ with r3 = alkyl or aryl.

Substituted: 4-phenylthiophenes can be used as intermediates for organic syntheses.

Chara kteristik of the known technical Eras unge n

Such substituted 4-phenyl-thiophenes have not yet been described.

It is known that Arylacetaldehyde react in the presence of sodium hydride with carbon disulfide and subsequent addition of methyl iodide to 3,3-bis (methylthio) -2-aryl-acroleinen, let [m. SAQUET, A, THUILLIER, Bull. Suction *. Qhinu Pr. 1966 , 1582], but it was not expected that by reaction with suitable compounds as the alkylating agent, a cyclization to appropriately substituted thiophenes.

The aim of the invention is novel substituted 4-phenylthiophenes which are prepared on the basis of readily available starting materials,

The invention has for its object to produce these new compounds according to a simple method,

ErfindungsgemäJB be substituted ^4-I> -phenyl-.thiophene of the general Formula I are prepared by bringing phenylacetaldehyde with a heterocumulene, such as carbon disulfide or Einein Isothiocyanatp in an aprotic solvent with addition of a base to the reaction and the resulting geminal Dithiolet III

a) with a halogen-active CH-acidic compound or

b) first with an alkyl halide and then with a halogen-active GH-acidic compound

bziw «, the monosodium salt V is reacted with a halogen-active G, H-acidic compound» After dilution of the reaction mixture mi t t of water, isolation of the oil formed and addition of methanolic sodium methylate solution is allowed to stand until the formation of the cyclic product I.

For example, sodium hydride is suitable as the base, for example dimethyl sulfoxide as solvent for dithiocarboxylation, while dimethylformamide is preferably used for thiocarbamoylation.

As halogen-active OH-acidic components, & halogeno-carbonyl compounds can be used «chloroacetonitrile or bromonitromethane»:

Equations 1 and 2 illustrate the method according to the invention, according to which, for example, the compounds of Table 1 can be represented.

Auaführungabeiapiele

5- (methoxycarbonyl methylthio) thiophene ~ -4-phenyl-2-carbonaäuremethyleater

 12 g of phenylacetaldehyde are removed in 100 ml of aqaol. Dissolved Dirnethylsulfoxid Man working under an inert gas seed pump 7.6 g of carbon disulfide and anachlößend 4.8 g of sodium hydride are added portionaweiae initially with stirring and cooling. To complete the reaction is stirred for 2 more hours. At room temperature. After the dropwise addition of 30.6 g of Bromesaigaäuremethyleater, it is stirred for a further 2 hrs. At room temperature, then poured into 300 ml Eiawaaser, decanted from the oily product and veraetzt with a warm methanoliachen Natriummet hylat Löaung. The aich forming Niederachlag is sucked off and Umkriatalliaiert. .

5-methylthio-4-phenyl-thiophene-2-carbonitrile

Analogously to Example 1. Anatelle of Bromeaaigaäuremethyleater initially be added dropwise 14.2 g of methyl iodide. The mixture is stirred for 1 h and then added 7.6 g of chloroacetonitrile ·

5-anilino-2- (4-ohlorbenzoyl) -4-phenyl ~ thiophen

12 g of phenylacetaldehyde, dissolved in 80 ml of abaol. Dimethylformamide, cooled to 0 ⁰ C and added with stirring portiona-

2.4 g of sodium hydride are then added. 13 * 5 g phenyl isothiocyanate are then added dropwise without extensive cooling. The mixture is then stirred for 2 more hours at room temperature, followed by 23 g of 4-g p-chlorophenacyl bromide dissolved in 50 ml of absolute dimethylformamide cooling zugetropf.t _e After a further 2 Std'n _e carries stirring the solution in 300 ml of ice water, decanted off and the residue with a warm methanolic sodium methoxide was added Lösunge the precipitate is filtered off and recrystallized _β

Table 1:

Schmp. G

recrystallized

Yield %

-COOCH ₃ · S-CH ₂ -R ² (R ² S GOOGH ₃ ) 62-63 GH ₃ OH 37 -GOOGH ₃ -S-GH ₂ -R ² (R ² : H) 69-70 GH ₃ OH 37, -G N -S-GH ₂ -R ² (R ² H) 99-100 CH ₃ OH 44 G ₆ H ₅ -CO -S-CH ₂ -R ² (R ² SH) 96 CH ₃ OH ³⁶ "* 6 4 ~ CO -NHR ³ (R ³ JC ₆ H ₅ ) 192-194. C ₂ H ₅ OH 31 NO ₂ V \ -S-CH ₂ ^ R ² (R ² SH) 79-81 GH ₃ OH 59

* * D * **

JU

Equation 1

U A-OH ₂ -GHO + 2 NaH + GS, II

GHO

III -.

1.

2 ·

-Sna "SNa

3.-H ₂ O

R ² -CH ₂ -i

IV

Equation 2:

II + NaH

₊ r3-

NCS

C = C:

CHO

, NHR

S Na

+ R-CH ₂ -X - H ₂ O

> 3

VI

Claims (3)

- 5 - Experience indanapruoh 1) A process for the preparation of substituted 4-phenylthiophenes of the general formula I in which R is an acyl, iger, nitro or nitrile group and Y 2) Method according to item 1, characterized in that find as heterocumulenes carbon disulfide and isothiocyanates use. 2 2 for an alkylthio group -S-GH ₂ -R in which R is hydrogen, alkyl, aryl or an acyl, ester, nitro or nitrile group, or an amino group -NHR- * with R ^ s alkyl or aryl , characterized in that phenylacetaldehyde with a Heterbkumulen in an aprotic Solvena with the addition of a base, reacted and the resulting geminal dithiolate III a) with a halogen-active CH-acidic compound or b) first with an alkyl halide and then with a halogen-active CH-acidic compound or the monosodium salt V is reacted with a halogen-active CH-acidic compound and then the reaction mixture diluted with Y / asser, the resulting oil is isolated and treated with methanolic sodium methylate solution, j 3) Method according to item 1, characterized in that as halogen-active GH-acidic compounds oL-halocarbonyl, chloroacetonitrile or Bromnitromethan be used. For this 2 pages formulas.