Thenyl Bromide

Campaigne et al. have used 3-thenyl bromide obtained by benzoyl peroxide-catalyzed, side-chain bromination of 3-methylthiophene with A -bromosuccinimide, as a starting material for 3-substituted thiophenes. - 22 3-Methylthiophene is now prepared commercially from itaconic acid. The reactive halogen in 3-thenyl bromide could be directly reacted with a variety of nucleophiles, such as cyanide, or malonate, to give more complex 3-substituted compounds. 3-Thenyl bromide was converted by the Sommelet reaction to 3-thio-phenealdehyde which, with silver oxide, was oxidized to 3-thio-... 

By reaction of 3-thienyllithium with magnesium bromide, the Grignard reagent, free from entrainment Grignard reagent, was obtained,- which is useful for the preparation of 3-acetothiophene by reaction with acetic anhydride at —70 0 and for the preparation of 3-t-butoxythiophene through reaction with t-butyl perbenzoate. It is the opinion of the present author that most 3-substituted thiophenes are prepared more conveniently from 3-thienyllithium than from 3-thenyl bromide. The latter method, however, is superior if the introduction of the 3-thenyl group is desired. 

Thenyl bromide and 2-pyridinealdehyde reacted to form a quaternary salt (182) which was cyclodehydrated to thieno(2,3-b)quin-azolinium bromide (183). ... 

Hexamethylene tetramine (77 g., 0.55 mole) is dissolved in 200 ml. of chloroform, and 88 g. (0.5 mole) of 3-thenyl bromide (p. 96) is added as rapidly as possible with shaking (Note 1). A reflux condenser is attached, and the mixture is refluxed over a steam bath for 30 minutes. After being cooled, the mixture of chloroform and crystalline product (Note 2) is poured into 250 ml. of water and stirred until all the salt dissolves. The chloroform layer is separated and washed twice with 125-ml. portions of water, and the combined water extracts are steam-distilled. When the distillate comes over clear (about 1 1. of distillate is usually collected), it is acidified with a little hydrochloric acid (Note 3) and extracted with three 100-ml. portions of ether. After drying over Drierite, the ether is evaporated, and the residue is distilled. 3-Thenaldehyde is collected at 72-78°/12 mm. or 195-199°/744 mm., = 1.5860 (Note 4). The yield is 30-40 g. (54-71%). 

Oxidation of the aldehyde was not used earlier because of the difficulty of obtaining the aldehyde, which is now readily available by the Sommelet synthesis from 3-thenyl bromide. Campaigne and LeSuer 7 also used alkaline permanganate as the oxidizing agent, but the yields decreased to 40-60%. The present procedure gives an over-all yield from 3-methylthiophene of about 45%. 

Unless the reaction mixture is maintained at strong reflux during this addition, considerable nuclear bromination occurs with a corresponding decrease in 3-thenyl bromide yield. 

If necessary to interrupt the procedure, the benzene solution of 3-thenyl bromide may be stored over calcium carbonate and distilled directly from the carbonate later. The addition of a little calcium carbonate before distillation avoids the formation of a difficultly removable tarry residue. 

The product contains a trace of 2-bromo-3-methylthio-phcne, but no 2-bromo-3-thenyl bromide, and is sufficiently... 

Synthesis of Compound I. As shown in Scheme II, 3-(thiophene-3-yl)propyl bromide can be prepared by a two-carbon homologation(2 ) of 3-thenyl bromide via reaction with diethyl malonate to form diethyl 3-thenylmalonate. This is followed by saponification, decarboxylation, reduction of acid to alcohol, (2 ) and replacement of the hydroxyl group with bromide by reacting with PBr3.(22) Compound 2 is synthesized by mono-quaternization of an excess of 4,4 -bipyridine with 3-(thiophene-3-yl)propyl bromide followed by N-methylation with CH3I. All the intermediates in Scheme II have been identified by NMR spectroscopy. 2 has been characterized by NMR and high resolution mass spectroscopy and by electrochemistry. 

To a suspension of 3.12 g of sodium amide in 50 ml dry toluene was added dropwise 12 g of 2-(dimethylamino)ethylaminopyridine. The mixture was refluxed for 2 hours, cooled to 50°C, and 21 g 3-thenyl bromide was added dropwise. When reaction subsided, the brownish-orange mixture was refluxed for 0.5 hour, cooled, and poured into 150 ml of water. The toluene layer was separated, extracted with 5% hydrochloric acid. This extract was saturated with potassium carbonate. The free base was extracted with ether, dried and fractionated. Yield of N,N-dimethyl-N -2-pyridinyl-N -(3-thienylmethyl)-l,2-ethanediamine 31%, boiling point 169-172°C/1 mm. 

Procedure. The 3-thenyl bromide is dissolved in the chloroform and the hexamethylenetetramine is added. The mixture is boiled for one hour, cooled, and the salt filtered off. The dry salt is dissolved in 500 ml. of hot water and the mixture steam distilled until one liter of distillate is collected. The distillate is acidified with dilute hydrochloric acid and... 

Tetraphenylarsonium chloride HYDROCHLORIDE, 30, 95 Tetraphenylethylene, 31, 104 2,2,3,3-Tetraphenylpropionitrile from diphenylacetonitrile and benzhydryl chloride, 39, 74 Tetra-K-propyltin, 36, 88 3-Thenaldehyde, 33, 93 3-Thenoic acid, 33, 94 3-Thenyl bromide, 33, 93, 96 7-Thiabicyclo(4.1.0)heptane, 32, 39 Thiobenzoic acid, 31,101 Thiobenzophenone, 35, 97 Thiocarbonyl perchloride, 32, 69 Thioether, preparation of dithiane,... 

Derivation Condensing /V,/V-dnnethylaminocthyl-a-aminopyridine with 3-thenyl bromide. 

The synthesis of the thieno[2,3-/>]quinolizinium ion (237) was effected in good yield from 2-formylpyridine and 3-thenyl bromide (Scheme 46). The same reaction of 2-thenyl chloride with 2-formylpyridine led to thieno[3,2-fc]quinolizinium bromide (238) but in extremely low yield (4%). 

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