Thiophenes tetrahydro-, reaction with

Thiophenes are best converted to the tetrahydro derivatives by the so-called ionic hydrogenation. This depends on the successive addition of a proton (from trifluoroacetic acid) and a hydride ion (from triethylsilane) (75T311). A subsequent improvement involved the use of HC1/A1C13 to form the thiophenium ion and then reaction with triethylsilane (78T1703) best results are obtained with the substrate/Et3SiH/AlCl3 ratio of 1 3 0.3. The mechanism of the reaction is shown in Scheme 43. Evidence for this has been provided by the use of Et3SiD, when D enters positions 3 and 5 in the product. 

Unusual electrophilic compounds containing sulfur are the S+—S+ dications S. yjjg reaction of dimethyl sulfide ditrifiate with dimethyl sulfide leads to the formation of tetramethyldisulfonium ditrifiate (101a). The same procedure starting from tetrahydrothiophene ditrifiate gives by reaction with tetrahydro thiophene the corresponding dication 101b (equation 105). 

Various Reactions in the Side-Chains of Thiophens. - The preparation of various iV-substituted thieno[3,2-/]morphans from 2,5-dimethylthieno[3,2-/Jmorphan has been described. Several thiophen isosteres of proto-berberine alkaloids have been prepared, starting from amides between 3-thienylacetic acid and substituted )3-phenylethylamine or 3-(3-thienyl)ethyl-amine, followed by classical cyclization to dihydroisoquinolines, reduction to the tetrahydro system, and Mannich-type reaction with formaldehyde. 

More complex structures can be derived from 1-tetralone through its conversion to (tetrahydro-l-oxo-2-naphthyl)ethanoic acid and subsequent reaction with a heteroaryllithium. Sequential cyclisation to the dibenzofuran or thiophene and propargylation affords fast fading 3,4-dihydronaphtho[2,l-/ [l]benzofuro[2,3-/r]naphtho[l,2-6]pyrans and thiophene analogues <00WOP77007>. 

Among other color reactions of thiophene, the following may be mentioned Liebermann reaction with nitrite and sulfuric acid (73) the very sensitive reaction with thaline (tetrahydro-/ -hydroxyquinoline methyl ether) and dilute nitric acid (74) reaction with sulfuric acid, copper (II) acetate, and lactic acid (75) and, especially, the reaction with ceric ammonium nitrate (76). Of course, this reaction is not specific (see also p. 170), but it allows the differentiation of isomeric thiophene derivatives. 

Insertion reactions of diazomethane with 1-chlorothioisochroman lead to 2-chloro-l,2,4,5-tetrahydro-3-benzothiepin and 1-chloromethyIthioiso-chroman. Other thioisochroman derivatives have been prepared by condensation reactions with the carbanion derived from 1-cyanothioiso-chroman. " A 1,4-disubstituted thioisochroman is postulated as the unstable intermediate involved in the conversion of o-divinylbenzene (67) into the benzo[c]thiophen derivative (68)." ... 

The discovery of junipal focused the attention of Sorensen, who had been investigating the occurrence of polyacetylenes in Com-positae, on the possibility that these acetylenes were accompanied by thiophenes. From Coreopsis grandiflora Hogg ex sweet, 2-phenyl 5-(1-propynyl) thiophene (240) was isolated and its structure confirmed by synthesis of the tetrahydro compound, 2-phenyl-5-n-propyl-thiophene. From the root of tansy, the cis and trans isomers of methyl 5-(l-propynyl)-2-thienylacrylate (241) have been isolated. The total synthesis of trans (241) was achieved by reacting junipal with methylcarbethoxy triphenylphosphonium bromide (Wittig reaction) Several monosubstituted thiophenes, (242), (243), and... 

In one route, tidopidine (1) was assembled via Sn2 displacement of 2-chlorobenzyl chloride (9) with 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (8). " The nucleophile 8 was synthesized by heating 2-thiophen-2-yl-ethylamine (6) with 1,3-dioxolane in the presence of concentrated hydrochloric acid. 1,3-Dioxolone gave better yields than with formaldehyde, paraformaldehyde and 1,3,5-ttioxane. The interesting transformation 6 —> 8 first involved the formation of the corresponding Mannich base 7, which then underwent a Pictet-Spengler type reaction to afford the ring-closure product 8. It was of interest to note that a possible intramolecular aminomethylation did not take place. 

In a closely related reaction, heating the trimethylamine salt of the condensation product of dihydroresorcinol and 5-ethoxymethylene-3-methylrhodanine with aqueous alkali affords 4,5,6,7-tetrahydro-benzo[6]thiophen-4-one-2-carboxylic acid (92), via the intermediate (91).846... 

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