Indole derivatives acidity

Phenylhydrazine condenses with acetoacetic ester to give a pyrazolone derivative which on methylation gives phenazone. The sulphonic acid similarly gives rise to the tartrazine dyestuffs. It is used to make indole derivatives by the Fischer process. 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

The indole ring is incorporated into the stmcture of the amino acid tryptophan [6912-86-3] (6) and occurs in proteins and in a wide variety of plant and animal metaboUtes. Much of the interest in the chemistry of indole is the result of efforts to understand the biological activity of indole derivatives in order to develop pharmaceutical appHcations. 

Apply indole derivatives dissolved in sodium bo- [105] rate buffer solution (c = 0 2 mol/1, pH 9 0) — ethanol (1 -I-1) Dip TLC plate in fluorescamine solution to just above starting zone (15 s) Then dry at room temperature and develop In case of indole amines followed by spraying with 40% perchloric acid... 

Three new papers bearing on the structure of strychnine have become available too late for inclusion in this summary of recent work. Woodward, Brehm and Nelson have compared the ultra-violet absorption spectra of strychnine and Leuchs s strychnone (p.. 559) and used the results for a discussion of the relationship of the two alkaloids. Prelog and Kathriner have investigated the oxidation of strychnine, i/t-strychnine and brucine by permanganate in weakly acid solution and Bailey and Robinson from a study of the brucones have confirmed the conclusion of Woodward et al. that Leuchs s strychnone is a true indole derivative. Mention must also be made of a paper by Clemo and King on new reduction products of strychnine, of which a preliminary account has been published with a summary of the ensuing discussion. 

Rauwolscine gives colour reactions like those of yohimbine and the absorption curves of the hydrochlorides of the two alkaloids are very similar. Heated to 300°/5 mm. rauwolscinic acid forms barman (p. 490) and 3-ethylindole and on fusion with potassium hydroxide decomposes into indole-2-carboxylic acid, isophthalic acid, barman and an unidentified indole derivative. Rauwolscine itself on distillation with zinc dust produces barman, 2-methylindole (scatole) and tsoquinoline. It is suggested that the alkaloid has the skeletal strueture suggested by Seholz (formula XIV, p. 508) for yohimbine, the positions of the hydroxyl and earbomethoxy grouf s being still imdetermined. 

R" = CH20H). The use of sodium borohydride in place of lithium aluminum hydride did not lead to ring closure but to 3-[j8-(A-l,2,3,4-tetrahydroisoquinolyl)ethyl]indole derivatives (53). Reductive cyclization by means of lithium aluminum hydride of the j8-(3-indolyl)ethyl-l-isoquinoline (52) to the pentacyclic tetrahydro-j8-carboline 49 (R = R = R" = H) has been reported. Strong acid alone sufficed to convert 52 into 54, the 0x0 derivative of 49. ... 

The dimerization reactions of 2-vinylindoles and their alcohol precursors have also been explored, giving rise to the formation of several dimeric structures, such as the 6,12-dihydroindolo[3,2-h]carbazole derivative 160, which was obtained on dimerization of 2-(a-hydroxyethyl)indole under acidic conditions (71JOC1759). 

During studies on the acid-induced formation of the alkaloid yuehchukene and related structures from pienylindoles, it was discovered that treatment of indole 173 with p-toluenesulfonic acid and silica gel leads to the formation of indolo-[3,2-b]carbazole 174 and the indole derivative 175 (Scheme 21). Similarly, the disubstituted product 176 could be isolated after TFA treatment of the substrate 177. Detailed mechanistic explanations have also been provided in this work (96T9455). 

Treatment of the indole derivative 290 with trifluoroacetic acid gave the addition product 291 that upon cyclization afforded the pyridoindole derivative 292 (81H713). Treatment of 290 which has a dioxopiperazine ring on C-3 with boron trifluoride etherate gave a mixture of pyrroloindole 293... 

Dimethylamino)-cinnamaldehyde - hydrochloric acid -I- indole derivatives... 

It can be concluded from the publications of Rohde [2] and Freund and Lebach [3, 4] that it was Ehrlich who first suggested the use of 4-(dimethylamino)-benzalde-hyde in the presence of hydrochloric acid for color reactions with methylketols that was found also to apply to indole derivatives [S]. Auterhoff [6] designated a reagent for urobilinogen, consisting of a solution of 2 g 4-(dimethylamino)-benzaldehyde in 20 percent hydrochloric acid, correctly as Ehrlich s solution. Hence, it is essentially correct to refer to all reagents which contmn these components as Ehrlich s reagent. 

Dimethylamino)-benzaldehyde — hydrochloric acid reacts less sensitively than 4-(dimethylamino)-cinnamaldehyde — hydrochloric acid in the detection of indole derivatives, but the former is better for differentiation of substances on account of the multiplicity of different color shades produced. 

Classical examples of this type of reaction are the various dimethylaminobenz-aldehyde reagents (q.v.) and vanillin-acid reagents, of which one, the vanillin-phosphoric acid reagent, is already included in Volume 1 a. The aldol condensation of estrogens is an example for the reaction mechanism (cf. Chapter 2, Table 6). According to Maiowan indole derivatives react in a similar manner [1]. Longo has postulated that catechins yield intensely colored triphenylmethane dyes [2]. 

Aromatic aldehydes react in basic as well acidic medium. Thus vanillin and primary amines yield Schiff s bases (cf. vanillin-potassium hydroxide reagent in Volume 1 a). Colored phenolates are formed at the same time. As would be expected secondary amines, indole derivatives and lysergic acid derivatives do not react. 

In the presence of strong acids catechins react with aromatic aldehydes to yield triphenylmethane dyes [14] according to Malowan [15] indole derivatives form the following condensation product ... 

For indole derivatives Dissolve 50 mg 4-(dimethylamino)-benz-aldehyde in 1 ml cone, sulfuric acid and make up to 100 ml with 95% ethanol [7]. 

From a commercial viewpoint the most important compounds of this class are the 3,3-(bisindol-3-yl)phthalides. The first synthesis47 involved Route B as described in Scheme 7, in which a second indole derivative condenses with the indolylbenzoylbenzoic acid in acetic anhydride. However, for the preparation of symmetrical derivatives it has been shown61 that a one-pot process, avoiding isolation of the intermediate and use of aluminum chloride, is more convenient. 

Eventually, indole acetic acid 2 was prepared from iodoaniline 28 and propargyl alcohol derivative 61 via the newly developed coupling reaction followed by a cyanide displacement-hydrolysis sequence, as shown in Scheme 4.16. 

Auxins Derivative of tryptophan - e.g. indole acetic acid. Controls H+/K+ balance and growth... 

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