Thiophene, 2,4-dibromo-, preparation

The bromination of 2-cyanothiophen with one equivalent of bromine in the presence of an excess of AICI3 gives 2-cyano-, 4-bromo-2-cyano-, 5-bromo-2-cyano-, and 4,5-dibromo-2-cyano-thiophen in the proportions 16 70 2 12, from which pure 4-bromo-2-cyanothiophen can easily be obtained. Nitration of 2-cyanothiophen in concentrated sulphuric acid led to mixtures of almost equal amounts of 4- and 5-nitrothiophen-2-carboxylic acid. The chloromethyl-ation of 2-acetylthiophen and 2-formylthiophen with ota -bis(chloromethyl) ether in 60—100% sulphuric acid has been studied. An increase in the acidity of the medium promoted the formation of 4-substituted products. From these products some otherwise difficultly obtainable 2,4-disubstituted thiophens were prepared. ... 

The bromination behavior of isomeric thienothiophenes (53-55) has been studied in detail. Both the [2,3-b] (53) and the [3,2-h](54) isomers reacted with one equivalent of NBS in acetic acid to give an a-monobrominated product, with some evidence of 2,5-dibromo species also being formed. With 2 mol of NBS these latter products were formed in good yield three molar equivalents led to 2,3,5-tribromothieno-[2,3-h]-and -[3,2-6]-thiophenes (Scheme 28). The monobromo compounds can also be prepared from lithium derivatives quenched with bromine [76AHC( 19) 123]. Apparently the [2,3-c]isomer (55) also reacted initially in the 2-position. 

Biedermann and Jacobson, who first prepared thieno[2,3-6]-thiophene (1) in 1886, characterized it as a 2,3,4,5-tetrabromo derivative with m.p. 172°. Later Capelle reported the isolation of a dibromo derivative of thienothiophene 1 with m.p. 122.5°, which was shown by Challenger and Harrison to be 2,3,5-tribromothieno[2,3-6]thiophene (m.p. 123°-124°). Capelle also obtained a tetrabromide, m.p. 223°, by bromination of the product of reaction of acetylene with sulfur. The tetrabromide seems to be identical with that prepared from the product of reaction of methane, acetylene, and hydrogen sulfide, m.p. 229°-230°, and is evidently 2,3,5,6-tetrabromothieno[3,2-6j-thiophene. ... 

Treatment of 2,3,5-tribromothieno[3,2-h]thiophene with n-butyl-lithium followed by hydrolysis produced 74% yield of 2,6-dibromo-thieno[3,2-h]thiophene, and treatment with zinc dust in glacial acetic acid formed 3-bromothieno[3,2-h]thiophene, containing unsubstituted thienothiophene 2 and the 2,6- bromo comixiund as impurities. Pure 3-bromothieno[3,2-fi]thiophene was isolated using preparative gaa-liquid chromatography. 2,3,5-Tribromothieno[2,3-6]thiophene similarly afforded 3-bromothieno[2,3-h]thiophene. 

Thiophene- and benzo[6]thiophene-carboxylic acids undergo all the normal reactions of an aromatic carboxylic acid (63AHC(1)1, 70AHC(11)177). They can be converted to acid chlorides, amides and esters the esters can be used to make hydrazides. Benzo[6]thiophene-2-carboxylic acid chloride has been converted to the methyl ketone with dimethylcadmium and to the diazoketone with diazomethane. Bromodecarboxylation of the silver salts (Hunsdiecker reaction) has been used to prepare the dibromo compounds (340) and (341). 

On heating a solution of 3,4-dibromo-4-nitro-4,5-dihydrobenzo[6]-thiophen-5-one (Section VI, 1,4) in benzene, 3-bromobenzo[6]thio-phene-4,5-quinone is obtained.497 The unstable product readily condenses with ethyl cyanoacetate in the presence of base to give 3-bromo-7-(carbethoxy cyanomethyl)benzo[6]thiophene-4,5-quinone. The 4-bromo-4-nitro-4,5-dihydrobenzo[6]thiophen-5-ones prepared by nitration of 3,4-dibromo-,152,421 4,6-dibromo-,152 3,4,6-tri-bromo-,421 and 2,3,4,6-tetrabromo-5-hydroxybenzo[6]thiophene421 decompose similarly to the corresponding 4,5-quinones on being boiled in benzene. 

Dibromo-dithieno[2,3-b 3,2 -d]thiophene was also prepared by the author and had a mp = 181-182°C after de-silyation of 4,4 -dibromo-5-trimethylsilane-dithieno[2,3-b 3, 2 ]thiophene. and C-NMR and MS data also provided. 

In furan and thiophene, the halogen enters the alpha position. The vapor-phase reaction of pyridine and bromine at 500° furnishes 2-bromo- and 2,6-dibromo-pyridines, and at 300°, 3 bromo- and 3,5-dibtomo-pyridines. 3-Bromopyridine is more conveniently prepared by pyrolysis of pyridine hydrobromide perbromide (40%). Similarly, quinoline yields 3-bromo-quinoline at 300° and 2-bromoquinoline at 500°. Pyrolysis of iso-quinoline hydrobromide perbromide gives the 4-bromo derivative (53%). ... 

Magnesium, Copper, and Tin. 3-Substituted 4-aryl-2,5-dibromo-thiophens give dimagnesium compounds, when the Grignard reagent is prepared by the entrainment method (simultaneous reaction with... 

Liu used a double halogen-lithium exchange to prepare diindolo[3,2-Z> 4,5-6 ] thiophenes (e.g., 139). For example, treatment of 3,3 -dibromo-2,2 -biindole 138 with n-butyllithium followed by quenching with bis(phenylsulfonyl) sulfide gave 139 (Scheme 29) [60]. 

Tetrathiabenzo[l,3-cfirst time by dimerization of thieno[2,3- >]thiophene (142) (92PS73). More recently, it was found that catalytic reduction of 3,4-dibromothieno[2,3-i]thiophene (227) with an excess of activated zinc in the presence of bis(triphenyl-phosphine)nickel(II) chloride and tetraethylammonium iodide afforded only 4,4 -dibromo-3,3-bis(thieno[2,3- )]thiophene) (228) (in a maximum yield of 28%) (89AG1254). However, the reaction in the presence of a larger amount of the nickel catalyst afforded also dipenatlene 225. Optimization of the reaction conditions made it possible to increase the yield of the latter to only 14%. An alternative procedure was employed to transform thienothiophene 227 into trimethylstannyl derivative 229. The reaction of thienothiophene 227 with organotin intermediate 229 in the presence of the palladium triphenylphosphine complex afforded dipentalene 225 (13% yield). Derivatives 226 were prepared by lithiation of... 

---