Thiophenes with isatin

Thienothiophenes undergo the indophenine reaction with isatin (see Section III,I). Oster reported that thieno[2,3-6]thiophene (1) gave a green product with a ratio of isatin to thienothiophene 1 1, and a blue substance with the ratio of the initial substances 2 1. Steinkopf and HempeP could not obtain this blue substance instead they isolated a brown material with the isatin to thienothiophene 1 ratio 2 3 at +50° they isolated a substance with the ratio 1 1 and at +70°, with ratio 1 2. Steinkopf and PetersdorP found that a reaction of 2-acetylthieno[2,3-6]thiophene with isatin produces 2- or 3-(2-thieno[2,3-6]thienyl) cinchoninic acid. The acid was decarboxylated to 2- or 3 2-thieno[2,3-6]thienyl)quinoline (the site of quinoline group in thienothiophene 1 molecule was not established). 

The benzene used should first be tested for thiophene with isatin and cone, sulphuric acid, and then redistilled and recrystallised traces of... 

A reaction of special historical interest, mentioned in the introduction to this chapter, is the condensation of thiophene with isatin in concentrated sulfuric acid, to give the deep blue indophenine as a mixture of geometrical isomers. ... 

More rarely, ions of type (97) form dimeric products (possibly by initial loss of nuclear protons) thus, thiophenes with two free a-positions, or free adjacent a- and (3-positions, give indophenines (e.g. 103) with isatin (104). This reaction is used as a test for thiophene, the so-called indophenine test . 

THTOPHENE. [CAS 110-02-1]. (CH C.H)2)S, formula weight 84.H, colorless liquid resembling benzene in odor, mp —30°C, bp 84°C. sp gr 1,070. Thiophene and its derivatives closely resemble benzene and its derivatives in physical ancl chemical properties. Thiophene is present in coal tar and is recovered in the benzene distillation fraction (up to about 0.5% of the benzene present). Its removal from benzene is accomplished by mixing with concentrated sulfuric acid, soluble thiophene sulfonic acid being formed. Thiophene gives a characteristic blue coloration with isatin in concentrated sulfuric add. 

Tetrahydrobenzo[6]thiophene-2-carboxaldehyde condenses with compounds containing a CH2CN group.436 2-Acetyl- and 2-propionyl-4,5,6,7-tetrahydrobenzo[6]thiophene undergo the Pfitzinger reaction with isatins.436 Attempts to prepare 2-cyano-4,5,6,7-tetra-... 

Compounds 109 and 110, containing two uncondensed or condensed thiophene rings, were synthesized with high yields from the corresponding ketones 111 and 112 and isatin 7 [77, 108], The bithiophene 117-119 [77, 108] or dibenzothiophene 120 [109] derivatives, containing two 4-quinolinecarboxylic acid residues as substituents, were easily obtained in the same way from the ketone 113 and the diketones 114-116 by condensation with isatin 7. 

A few historical data are interesting to recall in order to show the role of serendipity in this field. Among the re-electron-excessive five-membered heteroaromatics with one heteroatom (CR)4X, thiophene has physico-chemical properties so similar to those of benzene that until 1882/3 it stayed hidden as an impurity in the benzene obtained from coal tar. Then Victor Meyer discovered it serendipitously at what is nowadays the Eidgenossische Technische Hochschule in Zurich, during a lecture demonstration by the assistant Traugott Sandmeyer in front of undergraduates. It was believed at that time that the deep blue color produced by heating benzene with isatin and concentrated sulfuric acid (the... 

The acid and its derivatives do not give the usual colour reactions for thiophene with a sulphuric acid solution of isatin. Magnesium, barium and silver sdUs have been described. 

In thiophen the oxygen of furfuran is replaced by sulphur. Its name indicates its occurrence in crude benzene as obtained from coal tar. Coal tar benzene gives a blue color with isatin known as the indo-phenin reaction. This reaction is not given by benzene made from benzoic acid and it was found, by Victor Meyer, to be due to the presence... 

The presence of thiophene is made known through a color reaction with isatin, a compmmd related to indigo. The isatin reagent is prepared by dissolving 1 g of isatin in 100 ml of concentrated sulfuric acid. It is best to prepare a smaller amount of solution as needed. Add to 3 ml of commercial benzene 1 ml of isatin reagent. 

Isatin forms a blue condensation-product (indophenine) with thiophene. On reduction with ammonium sulphide, isatide C16H12N2O4 [16] is formed. With zinc powder in acetic-acid solution, isatin yields bydroisatinj by more energetic reducing-agents oxy- and dioxy-indol are formed. Chlorine and bromine react with isatin, forming chlorine and bromine derivatives respectively. Acetic anhydride produces an acetyl isatiu [15],... 

When thiophene is treated with isatin (667) and sulphuric acid a blue coloration is formed. The production of color in this way, the so-called indophenin reaction, led to the discovery of thiophene by Victor Meyer. Before thiophene was discovered it was thought that the reaction was characteristic of benzene. A certain sample of the hydrocarbon failed to give the test. On investigation it was found that the benzene used had been prepared from benzoic acid. As benzene obtained from coal-tar gave the test, it was evident that the color-reaction was produced by a substance mixed with the hydrocarbon. When benzene containing thiophene is shaken with concentrated sulphuric acid, the thiophene is more rapidly converted into a sulphonic acid than is the benzene. Thiophene is obtained from the sulphonic acid prepared in this way by heating the latter with water under pressure. 

A spectrophotometric method for determining thiophene in benzene is available as alternative to gas chromatography. The spectrometer used is capable of detecting absorbance in the range from 400 to 700 run with a repeatability of 0.005 absorbance units. Thiophene is reacted with isatin to form a colored compound. The quantitative determination is based on reading concentrations from master curve. 

Thiophene, the foundation of this book, had a tricky birth. It masqueraded as benzene from 1879 to 1882, when Maeyer [1] uncovered the subterfuge. It turned out that coal tar-derived benzene, when treated with isatin and sulfuric acid, produced a beautifully deep-blue precipitate, named indophenine. This pigment was claimed by Baeyer in 1879 [2] to be a qualitative test for benzene and was the product of the indophenine reaction . The pigment s structure was eventually shown to consist of a quinoid form of bithiopene, shown below. 

Pyrrole resembles thiophen in its ability to react with isatin and other compounds containing the grouping 00 00, in the presence of acids, to give deep blue products os Some authors have claimed that in the reaction with isatin two types of pyrrole blue are formed, and it is still not clear whether this is so or not. Pratesi s observed that blue products could be prepared from 2,3-dimethylpyrrole and cryptopyrrole, but not from phyllo-pyrrole, and favoured structures of type (29). However, Steinkopf and... 

With isatin in cone, sulfuric acid pyrroles produce the same blue color as thiophene. 

Thiophene and its derivatives, unless substituted at both a-positions, give a positive reaction with isatin in cone, sulfuric acid. Where both positions are free a blue color is formed if one a-position is substituted, but the adjacent j -position is free, the color is green or violet. The structure of the colored substances formed is probably similar to that of the products described in the literature (67, 68). 

Thiophene is reacted with isatin, under prescribed conditions, to form a colored compound. The compound is extracted into sulfuric acid, and the intensity of the color is measured spectrophotometrically. Thiophene concentration is obtained by correlation with knowns. 

Commercial benzene may contain thiophene C H S, b.p. 84°, which cannot be separated by distillation or by fractional crystallisation. The presence of thiophene may be detected by shaking 3 ml. of benzene with a solution of 10 mg. of isatin in 10 ml. of concentrated sulphuric acid and allowing the mixture to stand for a short time a bluish-green colouration is produced if thiophene is present. The thiophene may be removed from benzene by any of the following methods —... 

Properties.—Mobile, colourless liquid m. p. 5 4 b. p. So 4 sp. gr. o 874 at 20°. Coal-tar benzene usually contains a little thiophene, C4H4S, which may be detected by dissolving a few crystals of isatin (see p. 229) in concentrated sulphuiicacid and shaking up with the benzene. If thiophene is present, a blue colour is produced (indophenin reaction). 

Oximes and their derivatives are widely used in organic synthesis. A number of reviews are devoted to the chemistry and biological activity of oximes and their derivatives The synthesis, reactions and biological activity of oximes containing a heterocyclic substituent, e.g. furan and thiophene", indole and isatin, pyridine, pyrrole, quinoline and five-membered heterocycles with two heteroatoms have been reviewed. 

---