Copper® chloride thiophene

A copper-mediated cyclization of metallated thiophenes has been utilized to prepare polycyclic thiophenes and thiophene cyclophanes. Treatment of dibromide 106 in succession with M-butyllithium (halogen-metal exchange), zinc chloride (transmetallation), and copper chloride gave 7//-cyclopcnta[ 1,2-fc 4,3-6 dithiophene (107) <00H(52)761>. This conversion has also been achieved using a palladium-mediated cyclization performed in the presence of hexamethylditin . Copper-mediated cyclizations have also been applied to the syntheses of cyclopenta[2,l-6 3,4-A ]dithiophen-4-one (108) (three steps from 73) <00S1253> and cyclophane 109 <00CC2329>. 

The regioisomeric 4,4 -dipentoxy-2,2 -bithiophene 327 bearing the pentoxy groups in the outer /3-positions was synthesized in 70% yield by oxidative coupling of lithiated 3-pentoxythiophene 321 with copper chloride. 4-Pentoxy-2-thiophene-boronic acid 326 which was synthesized from 3-pentoxythiophene 321, lithiumdiiso-propylamid and trimethylborate was coupled with I-Tj-I 54 and I-T2—I 306,... 

Compound 145 on lithiation <1999SM(102)987> and subsequent reaction with carbon dioxide afforded compound 146. Sandmeyer reaction of 2-bromodi thieno[3,2-A2, 3 -with copper(l)cyanide in hot iV-methyl pyrrolidine (NMP) gave the corresponding nitrile 148 which was then converted to the tetrazole 149 with a mixture of sodium azide and ammonium chloride in NMP in low overall yield (Scheme 14) <2001JMC1625>. 

Note 5) is equipped with a powerful mechanical stirrer and a thermometer and is immersed to a depth of 20 cm. in an ice bath. A mixture of 11. of thiophene-free benzene and 2 1. of 6 A hydrochloric acid is placed in the copper vessel. The above reaction mixture is added to the vigorously stirred contents of the copper can at such a rate that the temperature does not rise above 25° (about two hours is required). When the addition is. complete, the reaction flask is rinsed with a little ice water, and the rinsings are added to the hydrolysis mixture. Stirring is continued for ten minutes longer. The benzene layer is decanted, and the aqueous layer is diluted with 1 1. of ice water. The aqueous layer is extracted with 500 cc. of benzene and is discarded. The combined benzene solutions are washed with 250 cc. of ice-cold hydrochloric acid and are dried for two hours in a stoppered flask over 250 g. of anhydrous calcium chloride. 

Later Gronowitz and Maltesson reported the extension of this method to the preparation of thieno[2,3-6]thiophene (1) derivatives. A mixture of 3-(3-thienyl)acrylic acid, thionyl chloride, and pyridine was heated for 24 hours. 2-Chloro-3-(3-thienyl)-acrylic acid (4.5%), 3,5-dichlorothieno[2,3-6]thiophene-2-carbonyl chloride (99) (9.5%), 3-chlorothieno[2,3-Z)]thiophene-2-carbonyl chloride (100) (79.1%), and other compounds were detected by GLC among the reaction products [Eq. (31)]. Hydrolysis of the reaction mixture gave 3-chlorothieno[2,3-Z>]thiophene-2-carboxylic acid in 63% yield dechlorination of the latter by copper in propionic acid converted it into thieno[2,3-6]thiophene-2-carboxylic acid. 

Nucleophilic substitution procedures are also of use of the synthesis of j3-chlorinated thiophenes. Copper(I) chloride converted 3-bromothio-phene into its chloro analogue. Such reactions are best carried out in an... 

In some cases, the reaction of silicon and methanol has been optimized for formation of (MeO)4Si. As discussed above, thiophene addition favored formation of (MeO SiH. Both thiophene and propyl chloride poison copper copper poisoning seems to favor formation of the trialkoxysilane. High-temperature pretreatment disfavors trialkoxysilane formation copper is formed on the surface of the silicon during pretreatment at 450 °C98. Metallic Cu catalyzes dehydrogenation of alcohols and favors formation of (RO)4Si. Workers from Tonen Corporation reported 50% conversion of silicon to make (MeO Si with 92% selectivity if silicon, methanol and Cu(OMe)2 were pretreated (lower conversion and selectivity without pretreatment) and then reacted at 180 °C and 1 atmosphere99. 

To a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (5.30 g, 16.6 mmol), in anhydrous DMF (5.0 ml) was added (R)-N-hydroxy-N-(3-butyn-2-yl)urea (2.12 g, 16.6 mmol), triphenylphosphine (84.0 mg, 0.32 mmol), bis(acetonitrile)palladium(II) chloride (40.0 mg, 0.16 mmol), copper(I) iodide (16.0 mg, 0.08 mmol), and diethylamine (5.6 ml). The mixture was stirred under nitrogen at room temperature for 22 h and concentrated in vacuum at 32°C. The residue was subjected to chromatography on silica eluting with 2-7% MeOH in CH2CI2, crystallization from ethyl acetate-hexane and trituration in CH2CI2 to afford (R)-N- 3-[5-(4-fluorophenylmethyl)thien-2-yl]-l-methyl-2-propynylVN-hydroxyurea as a cream-colored solid 0.94 g (18%), melting point 135°-136°C, (dec). 

Dichloromaleimide is converted at or below ambient temperature to a thieno-pyrrole by malononitrile-methoxide, and then hydrogen sulphide [3378]. Several dithienothiophenes are synthesized by oxidative cyclization of the lith-iated intermediates, but when the latter are unstable, the dibromosulphides may be treated with butyllithium and copper(II) chloride [2287]. The chlorodibromo-quinoline (81.2) is efficiently converted into the fused thiophene when heated with thiourea in a protic solvent [2873]. 

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