Thiophen Analogues of Quinoline and Related Compounds

Thiophen Analogues of Quinoline and Related Compounds.—Convenient methods for the synthesis of the thiophen analogues of quinoline have been worked out. By the condensation of 2- and 3-thienylanunonium hexachlorostannates with malonic aldehyde tetraethyl acetal, thieno-[2,3-6]pyridine (538) and thieno[3,2-6]pyridine (539) were obtained in 44% and 77% yields. With other /5-dicarbonyl compotmds, substituted derivatives were obtained. Thus, acetoacetaldehyde dimethyl acetal gave 

Side-chain chlorination to 2,3-dichloromethylpyridine with JV-chloro-succinimide followed by ring-closure with sodium sulphide, oxidation to the sulphoxide with phenyliodonium chloride, and dehydration on AI2O3 according to the method of Cava gave (540). Curiously, attempts to prepare the benzo-analogue (541) by the same method were unsuccessful. However, the transient existence of (541) could be demonstrated by trapping with A -phenylmaleimide.  

Electrophilic substitution reactions of (538) and (539) have been studied. Bromination of (538) gave the 2,3-dibromo-derivative, whereas reaction with deuteriosulphuric acid gave fastest D-H exchange at C-3 and slower exchange at C-2.  

Both (538) and (539) were nitrated in the 3-position in 50% yield by means of nitric acid in sulphuric acid. The nitro-deiivatives were reduced to acetylamino-compounds. The results of electrophilic substitution were in agreement with simple MO calculations, and detailed n.m.r. data for (538)—(540) are given. The reaction of (538) with methyl- 

The 5-acetyl derivative of (538) has been converted into the 5-NHj, 5-CO2H, and 5-CH2C02H compounds. From the amino-compound the 5-bromo-derivative was obtained upon diazotization, which upon treatment with potassium amide in liquid ammonia gave a mixture of the 4-amino-(major) and 5-amino-isomers. The compound (538) was converted into the iST-oxide, which upon nitration in sulphuric acid gave 4-nitrothieno-[2,3-Z ]pyridine 7-oxide. Nitration in acetic acid, on the other hand, gave the isomeric 5-nitro-derivative. Several reactions were carried out with these nitro-compounds. In a manner similar to that described for (538) and (539), the compounds (542)—(544) were prepared from 3-aminobenzo[6]-thiophen, 2-aminothieno[2,3- ]thiophen, and 5-aminobenzo[6]thiophen 

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